environmental factors and semen quality - lodz
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IJOMEH 2009;22(4) 305
R E v I E w P a P E R s
International Journal of Occupational Medicine and Environmental Health 2009;22(4):305 – 329DOI 10.2478/v10001-009-0036-1
ENVIRONMENTAL FACTORS AND SEMEN QUALITYJOANNA JUREWICZ1, WOJCIECH HANKE1,2, MICHAŁ RADWAN3, and JENS PETER BONDE4
1 Nofer Institute of Occupational Medicine, Łódź, Poland Department of Environmental Epidemiology2 Medical University of Lodz, Łódź, Poland Department of Informatics and Medical Statistics3 Polish Mother’s Memorial Hospital — Research Institute, Łódź, Poland Department of Operative and Endoscopic Gynecology4 Bispebjerg Universty Hospital, Copenhagen, Denmark Department of Occupational and Environmental Medicine
AbstractObjectives: An increasing number of reports suggest that chemical and physical agents in the environment, introduced and spread by human activity, may affect male fertility in humans. This article aims at evaluating the impact of environ-mental exposures (pesticides, phthalates, PCBs, air pollution, trihalomethanes (THMs), mobile phones) on semen quality, by reviewing most recent published literature. Materials and Methods: Epidemiological studies focusing on exposure to environmental factors and semen quality for the last ten years were identified by a search of the Pubmed, Medline, Ebsco, Agricola and Toxnet literature bases. Results: The results from the presented studies suggest that there are strong and rather consistent indications that some pesticides besides DBCP (e.g. DDT/Dichlorodiphenyldichloroethylene [DDE], eth-ylenedibromide, organophosphates) affects sperm count. PCBs are detrimental to sperm motility. In case of air pollution, studies suggest a link between ambient air pollutants and various semen characteristics. Additional research is needed to corroborate this association and to establish the causal agents. Results of few studies on subfertile men demonstrate associ-ations between phthalate levels commonly experienced by the public and impaired sperm quality (impact on sperm concen-tration, morphology, motility), but the findings have not been corroborated in studies of men from the general population. Mobile phones might adversely affect the quality of semen by decreasing mostly motility but also the sperm counts, viability and morphology. In spite of their consistent results, most of the studies are rather small. Association between exposure to THMs and poor semen quality was not observed. Conclusions: Epidemiological studies suggest awareness of environ-mental factors which may affect semen quality. In case both of well proven and disputable reproductive and developmental hazards, it is necessary to prevent parental exposure to the agents associated with those hazards.
Key words:Environmental factors, Semen quality, Environmental exposure
This study was performed under the project “Exposure to environmental hazards and the risk of male infertility — multicenter national study in Poland.” supported by the Ministry of Science and Higher Education, Poland, from grant no. PBZ-MEiN-/8/2//2006; contract no. K140/P01/2007/1.2.1.2.Received: September 4, 2009. Accepted: October 12, 2009.Address reprint request to J. Jurewicz, Department of Environmental Epidemiology, Nofer Institute of Occupational Health, św. Teresy 8, 91-348, Łódź, Poland (e-mail: [email protected]).
INTRODUCTION
Male reproductive function in the general population has
attracted increasing attention due to reports indicating
increased occurrence of testicular cancer, cryptorchid-
ism and hypospadias across some time periods in some
populations past 50 years [1,2]. Reports indicating declin-
ing sperm counts in some regions [3,4] have also greatly
stimulated hypotheses that environmental pollutants may
impair male fertility [5].
The discovery in 1977 of the severe spermatotoxic effect of
the nematocide dibromochloropropane (DBCP) among
workers at a chemical plant [6] initiated several studies of
occupational and environmental risks to male reproduc-
tive function. Although for several decades semen qual-
ity has been used as a marker of male reproductive func-
R E v I E w P a P E R s J. JUREwICZ ET aL.
IJOMEH 2009;22(4)306
between a given environmental exposure and measures of male reproductive function in terms of semen quality for the last ten years. The period was chosen to reflect find-ings over the past ten years during which new techniques have emerged for measuring exposures and health effects in reproductive and environmental epidemiology studies.
RESULTS
Air pollutionThe major air pollutants in Europe and North America are sulphur dioxide (SO2), nitrogen oxides (NOx), particu-late matter (PM) and ozone (O3). Air pollutants can be in the form of solid particles, liquid droplets, or gases. In addition, they may be natural or man-made. Sources of air pollution refer to the various locations, activities or factors which are responsible for the releasing of pollutants into the atmosphere. Several studies addressing links between ambient air pol-lution and semen quality have been published past few years in the Czech Republic [13–15] and in USA, Los Angeles [16] (Table 1). Two hundred seventy two young Czech men exposed to high levels of air contaminants in the Teplice region were more likely to have abnormal sperm morphology and sperm chromatin structure than were those who lived in a city (Prachatice) with less air pollution. The authors observed a reduced percentage of sperm with normal morphology and proportionately more sperm with abnormal chromatin in men from Teplice re-gion [13]. The other study conducted in the same region of Czech Republic investigated whether the polluted air in the Teplice district is related to abnormal morphology in males living in this district [14]. More than 300 men living in the Teplice district and in the control district of Prachatice were examined between 1992 and 1994, in au-tumn and at the end of winter. Significantly increased fre-quency of sperm with abnormal morphology and reduced motility was observed in men with medium and high expo-sure to air pollution. More intensively exposed males also had significantly higher frequency of disomy in chromo-somes X, XY, and Y [14]. The same young men from Tep-lice were sampled up to seven times over 2 years, allowing
tion in case of environmental exposure, the data are still limited [7,8]. An obvious consequence of exposure to reproductive toxicants is infertility. Infertility is defined as inability to conceive after a year of sexual intercourse without the use of contraceptives. A male contributory factor is involved in approximately half of these cases [9], but most of the causes of reduced semen quality and other disturbances of male reproductive function are unknown [10]. Current studies, as reviewed by Sheiner et al. (2003) [11] and Jensen et al. (2006) [12] show that variety of envi-(2006) [12] show that variety of envi-ronmental and occupational exposures may impair male fertility. During past years male reproductive function has been addressed in relation to a number of environmen-tal exposures that have only to a very limited extent been investigated or reviewed earlier. These exposures and conditions include air pollution and drinking water pol-lutants, biopersistent organochlorines, trihalomethanes, phthalates and high frequency electromagnetic radiation related to use of mobile phones. The objective of this pa-per is to review the literature in order to update current state of the art knowledge on hazards to male reproduc-tive function.
MATERIALS AND METHODS
Epidemiological studies focused on the environmental factors and male fertility were identified by a search of the Pubmed, Medline, Ebsco, Agricola and Toxnet litera-ture databases. Hand search was a second search method used to explore the references of retrieved articles. The combination of key words used were: semen quality, en-vironmental exposure, air pollution, exposure to: phtha-lates, persistent organochlorine pollutants, tap water, mobile phones and pesticides. From each study, the fol-lowing information was abstracted: study population, type of outcome (sperm count, volume, concentration, sperm density, semen motility, morphology, aneuploidy, level of sexual hormones), type of exposure and methods used for its assessment (including biomarkers). Finally in this re-view were included human studies published in English in peer reviewed journals with original information on links
ENvIRONMENTaL FaCTORs aND sEMEN QUaLITY R E v I E w P a P E R s
IJOMEH 2009;22(4) 307
Tabl
e 1. S
emen
qua
lity a
nd ai
r pol
lutio
n
Stud
y pop
ulat
ion
Type
of s
tudy
Defi
nitio
n of
expo
sure
Sem
en an
alysis
Conf
ound
ers
Resu
ltsRe
fere
nces
Czec
h Re
publ
ic 21
5 you
ng m
en
(18 y
ears
of ag
e)
from
Tepl
ice re
gion
(indu
strial
ized
distr
ict)
and
193 f
rom
Pra
chat
ice
regio
n (ru
ral d
istric
t)
Pros
pecti
ve
coho
rtAi
r pol
lutio
n da
ta
were
obt
ained
from
air
mon
itorin
g sta
tions
Sem
en vo
lum
e, sp
erm
co
ncen
tratio
n, to
tal
num
ber o
f spe
rm p
er
sam
ple,
perc
enta
ge o
f m
otile
sper
m, p
erce
ntag
e of
sper
m w
ith n
orm
al m
orph
olog
y and
pe
rcen
tage
with
nor
mal
head
mor
phol
ogy
Seas
onali
ty, ag
e at
dona
tion,
smok
ing
Redu
ced
perc
enta
ge o
f spe
rm
with
nor
mal
mor
phol
ogy a
nd
prop
ortio
nate
ly m
ore s
perm
with
ab
norm
al ch
rom
atin
in m
en fr
om
Tepl
ice re
gion
was o
bser
ved
[13]
Czec
h Re
publ
ic 32
5 male
s 18-
year
-old
liv
ing i
n th
e Tep
lice d
istric
t (in
dustr
ialize
d di
strict
) an
d in
the c
ontro
l reg
ion
of P
rach
atice
(rur
al di
strict
)
Pros
pecti
ve
coho
rtAi
r pol
lutio
n da
ta
were
obt
ained
from
air
mon
itorin
g sta
tions
Sem
en vo
lum
e, pH
, m
otili
ty, n
umbe
r an
d m
orph
olog
y of
sper
mat
ozoa
, ane
uplo
idy
Seas
onali
ty, ag
e at
dona
tion,
smok
ing
Sign
ifica
ntly
incr
ease
d fre
quen
cy o
f sp
erm
with
abno
rmal
mor
phol
ogy
and
redu
ced
mot
ility
was o
bser
ved
in
men
with
med
ium
and
high
expo
sure
fo
r air
pollu
tion.
Mor
e int
ensiv
ely
expo
sed
male
s also
had
sign
ifica
ntly
high
er fr
eque
ncy o
f diso
my i
n ch
rom
osom
es X
, XY,
and
Y
[14]
Czec
h Re
publ
ic 36
youn
g men
(18 y
ears
of
age)
from
Tepl
ice re
gion
(indu
strial
ized
distr
ict)
Pros
pecti
ve
coho
rtAi
r pol
lutio
n da
ta
were
obt
ained
from
air
mon
itorin
g sta
tions
Sper
m co
ncen
tratio
n,
sper
m co
unt,
volu
me,
mot
ility,
sper
m
mor
phol
ogy,
aneu
ploi
dy
Seas
onali
ty, ag
e at
dona
tion,
smok
ing
A sig
nific
ant a
ssocia
tion
was f
ound
be
twee
n ex
posu
re to
per
iods
of h
igh
air p
ollu
tion
(at o
r abo
ve th
e upp
er
limit
of U
S air
qua
lity s
tand
ards
) and
th
e per
cent
age o
f spe
rm w
ith D
NA
fragm
enta
tion
acco
rdin
g to
sper
m
chro
mat
in st
ructu
re as
say (
SCSA
). O
ther
sem
en m
easu
res w
ere n
ot
asso
ciate
d wi
th ai
r pol
lutio
n.
[15]
Uni
ted
Stat
es, C
alifo
rnia
48 se
men
sam
ples
co
llecte
d fro
m sp
erm
do
nors
Cros
s-sec
tiona
lAi
r pol
lutio
n lev
els (o
zone
, ni
troge
n di
oxid
e, ca
rbon
m
onox
ide a
nd p
artic
ulat
e m
atte
r) we
re o
btain
ed
from
air m
onito
ring
statio
ns
Sem
en vo
lum
e, sp
erm
co
ncen
tratio
n, m
otili
ty,
sper
m m
orph
olog
y
Dat
e of b
irth,
se
ason
ality,
age a
t do
natio
n
A sig
nific
ant n
egat
ive co
rrelat
ion
betw
een
ozon
e lev
els at
0–9,
10–1
4 an
d 70
–90 d
ays b
efor
e don
atio
n an
d av
erag
e spe
rm co
ncen
tratio
n wa
s ob
serv
ed
[16]
R E v I E w P a P E R s J. JUREwICZ ET aL.
IJOMEH 2009;22(4)308
(POCs), has been hypothesized. In animal studies, POCs were found to have adverse effects on male reproductive function. The studies on exposure to organochlorine com-pounds and semen quality suggested association between polychlorinated biphenyls (PCBs) exposure and poor sperm quality. The findings of the pilot study carried out in the Boston area population were also indicative of an as-sociation between PCBs and p,p’-dichlorodiphenyldichloro-ethylene (p,p’-DDE) and abnormal sperm count, motility and morphology [19]. The total motile sperm counts were inversely proportional to the PCB concentrations and were significantly lower among infertile male than those of the controls [20]. Also, in a study performed by Dallinga et al. among 65 males with fertility problems, sperm count and motility were inversely related to the sum of PCB con-geners [21] (Table 2).A strong and monotonically increasing DNA fragmentation index with increasing serum levels of 2,2’,4,4’,5,5’-hexa-chlorobiphenyl (CB-153) was found in a study performed by Spanò et al. (2005) [22]. Sperm motility was also in-versely related to the lipid adjusted serum concentration of CB-153 among men in each of four regions (Greenland, Sweden, Warsaw and Ukrania), which is consistent with several earlier findings and results of animal studies [23] (Table 2). Thus, there is fairly strong evidence to suggest that persistent organic pollutants interfere with sperm motility, although the causal agent cannot be identified because of a strong correlation in serum concentration of a wide number of biopersistent pollutants [24].In a study of young fishermen from the coastal stretch-es of Sweden prostate-specific antigen (PSA), neutral α-glucosidase (NAG), fructose and zinc levels were anal-ysed. There was a significant linear association between CB-153 and total amount of PSA. With age, abstinence time and smoking included in the model the associa-tion became non-significant [25]. The same author per-formed also study among 176 Swedish fishermen (with low and high consumption of fatty fish). A significantly lower % DNA fragmentation index (DFI) was found in the lowest CB-153 quintile (<113 ng/g lipid) compared with the other quintiles; there was a similar tendency, al-though not statistically significant, between % DFI and
evaluation of semen quality after periods of exposure to both low and high air pollution. Using repeated measures analysis, a significant association was found between ex-posure to periods of high air pollution (at or above the upper limit of US air quality standards) and the percent-age of sperm with DNA fragmentation according to sperm chromatin structure assay (SCSA). Other semen measures were not associated with air pollution [15]The relationship between air pollutant levels and semen quality was also evaluated over 2-year period in Los An-geles, by analysing repeated semen samples collected by sperm donors. Semen analysis data derived from 48 semen samples provided by sperm donors were correlated with air pollution level (ozone, nitrogen dioxide, carbon mon-oxide, particulate matter). There was a significant negative correlation between ozone levels at 0–9, 10–14 and 70–90 days before donation and average sperm concentration, which was adjusted for donor’s birth date, age at donation, temperature and seasonality [16]. However, several occu-pational studies of TIG (tungsten inert gas) welders with exposure levels to ozone that are several orders of mag-nitude higher have not revealed reduced sperm counts in exposed men [18]. Summing up, while some studies suggest a link between ambient air pollutants and various semen characteristics like reduced percentage of sperm with normal morphol-ogy and proportionately more sperm with abnormal chro-matin and reduction of motility, additional research is needed to corroborate this association and to establish the causal agents.
Organochlorine contaminants, dioxins and polychlorinated biphenylsOrganochlorines were widely used worldwide from 1940 through 1970s, but most have been eliminated or restricted in use after recognition of their persistence in the environment, bioaccumulation in animals and humans and toxicity in laboratory animals and wildlife. Exposure mainly occurs through ingestion of contaminated food, but can also occur through dermal contact and inha-lation. A time-related deterioration in male reproductive function caused by exposure to persistent organochlorines
ENvIRONMENTaL FaCTORs aND sEMEN QUaLITY R E v I E w P a P E R s
IJOMEH 2009;22(4) 309
to DBPs. Exposure to DBPs was evaluated by incorporat-ing data on water consumption, bathing and showering with concentrations measured in tap water. No consistent pattern was found of increased abnormal semen quality (sperm concentration and sperm count) with elevated ex-posure to trihalomethanes or haloacetic acids [34]. In the second study the relationship between THMs and semen quality was examined in 157 healthy men from couples without known risk factors for infertility. Total THM levels were assigned based on water utility measurements taken during the 90 days preceding semen collection. THM level was not associated with decrements in semen quality. Only for motility, a small decrease for every unit increase in bromodichloromethane exposure level was found [35].Based on presented results, there seems to be no associa-tion between exposure to THMs and poor semen quality (sperm concentration and sperm count). As the number of studies is limited, further studies of the effect of THMs on semen quality are needed.
PesticidesPesticides form a large group of heterogeneous chemicals, which are used to kill insects, weed, fungi and rodents. On the one hand these substances bring a significant public health benefit by increasing productivity in the food indus-try and decreasing the incidence of diseases. Pesticides in general may directly damage spermato-zoa, alter Steroli cell or Laydig cell function, or disrupt the endocrine function in any stage of hormone regula-tion (hormone synthesis, release, storage, transport and clearance, receptor recognition and binding) [36]. Clear effects on male fertility have been demonstrated for some pesticides: dibromochloropropane [4], ethylene dibromide [37], organophosphorus [38,39], alochlor, me-tochlor, 2,4-D, atrazine [40], fenvalerate [41], carbaryl, chlorpyrifos [42]. The results of the recent studies performed in Denmark, China and Mexico indicated that exposure to pesticides (however not confirmed by exposure measurements) in-creased the risk of specific morphological abnormalities of the sperm and decreased sperm count per ejaculate and the percentage of viable sperm. No effects of pesticide
p,p’-DDE [26]. In the other cross-sectional study in Swe-den, negative correlations between CB-153 levels and both the testosterone and sperm motility were found [27] (Table 2).The results of the presented studies suggest that there is an association between exposure and poor sperm qual-ity, especially an inverse relationship was found between sperm motility and the concentration of PCBs, while other effects (sperm count and morphology) are rather uncer-tain. Increasing DNA fragmentation index with increasing serum levels of CB-153 was also found. On the other hand, no effects of concentration of CB-153 and p,p’-DDE on sperm concentration and prostate-specific antigen (PSA) were observed.
Trihalomethanes in tap waterTrihalomethanes (THMs) are a byproduct of the water treatment process. They are formed when natural organic material reacts with chlorine used to treat the water. This reaction produces “disinfection by-products” (DBPs) the most common of which are trihalomethanes (THMs). THMs such as chloroform, bromoform, chlorodibro-momethane, bromodichloromethane, are the most preva-lent and routinely measured class of DBPs found in the water [27]. Routes of exposure to THMs include dermal absorption during hand washing and bathing, inhalation during showering and ingestion of drinking water [28]. Animal studies have consistently demonstrated an as-sociation between oral exposure to DBPs including ha-loacetic acids (HAAs) and trihalomethanes and adverse effects in male reproductive system: acute spermatoxicity, impaired reproductive competence, sperm quality [29], delayed spermiation and distorted sperm motility and morphology [30], histopathologic changes in testis and epididymis [31], transient subfertility [32], altered sperm production and epididymal tubule changes [33].Contrary to large amount of evidences on the detrimental effects of DBPs on male reproductive function in animals, two so far completed human studies have not supported these findings [34,35] (Table 3). In one cohort study per-formed in United States the semen quality was evaluated among 228 fertile men with different profiles of exposure
R E v I E w P a P E R s J. JUREwICZ ET aL.
IJOMEH 2009;22(4)310
Tabl
e 2. E
xpos
ure t
o or
gano
chlo
rine c
onta
min
ants,
dio
xins,
polyc
hlor
inat
ed b
iphe
nyls
and
sem
en q
ualit
y
Stud
y pop
ulat
ion
Type
of s
tudy
Defi
nitio
n of
expo
sure
Sem
en an
alysis
Conf
ound
ers
Resu
ltsRe
fere
nces
Uni
ted
Stat
es
29 su
bjec
ts fro
m
Mas
sach
uset
ts G
ener
al H
ospi
tal A
ndro
logy
La
bora
tory
inclu
ding
18
subj
ects
with
nor
mal
sper
mat
ozoa
Cros
s-sec
-tio
nal
pilo
t stu
dy
Bloo
d se
rum
sam
ples
wer
e ana
lysed
fo
r PCB
, p,p
-DD
E an
d H
CBSp
erm
conc
entra
tion,
sp
erm
coun
t, vo
lum
e,
mot
ility,
sper
m
mor
phol
ogy
Age,
smok
ing,
absti
nenc
e tim
eAn
asso
ciatio
n be
twee
n PC
Bs an
d p,
p’-D
DE
and
abno
rmal
sper
m
coun
t, m
otili
ty an
d m
orph
olog
y was
de
tecte
d
[19]
Indi
a 21 in
ferti
le m
en w
ith
“une
xplai
ned
male
facto
r”
and
32 fe
rtile
cont
rols
were
exam
ined
Cros
s-sec
-tio
nal
PCBs
wer
e esti
mat
ed in
sem
inal
plas
ma
Tota
l mot
ile sp
erm
coun
tAg
e, sm
okin
g, ab
stine
nce t
ime,
diet
PCBs
wer
e det
ecte
d in
sem
inal
plas
ma o
f inf
ertil
e men
but
abse
nt
from
cont
rols.
Spe
rm q
uant
ity an
d qu
ality
were
sign
ifica
ntly
lowe
r in
infe
rtile
men
com
pare
d to
cont
rols.
Th
e high
est a
vera
ge P
CB co
ncen
-tra
tions
wer
e fou
nd in
fish
-eat
ing
urba
n dw
eller
s, fo
llowe
d in
succ
es-
sion
by fi
sh-e
atin
g rur
al dw
eller
s, no
n fis
h-ea
ting u
rban
dwe
llers
and
non
fish-
eatin
g rur
al dw
eller
s. Th
e to
tal m
otile
sper
m co
unts
were
in
verse
ly pr
opor
tiona
l to
the P
CB
conc
entra
tions
and
were
sign
ifica
nt-
ly lo
wer t
han
thos
e of t
he re
spec
tive
cont
rols
[20]
Neth
erlan
ds
A to
tal o
f 65 m
ale
coun
terp
arts
of co
uples
vis
iting
the M
aastr
icht
Uni
versi
ty H
ospi
tal f
or
ferti
lity t
reat
men
t wer
e se
lecte
d fo
r this
study
. 31
men
with
nor
mal
sper
m
quali
ty an
d 34
with
very
po
or se
men
qua
lity
Cros
s-sec
-tio
nal
Bloo
d sa
mpl
es w
ere i
nves
tigat
ed w
ith
rega
rd to
org
anoc
hlor
ine c
ompo
unds
: he
xach
loro
benz
ene (
HCB
),
p,p’-D
DE:
1,1-d
ichlo
ro-2
,2-bi
s (p
-chlo
roph
enyl)
ethy
lene p,p
’-DD
T:
1,1,1-
trich
loro
-2,2-
bis(p
-chlo
roph
enyl)
ethy
lene,
2,3’,4
,4’,5-
pent
achl
orob
iphe
-ny
l (PC
B-11
8), 2
,2’,4,
4’,5,5
’-hex
achl
o-ro
biph
enyl (P
CB-1
53),
2,2’,3
,4,4’,
5-he
xach
loro
biph
enyl
(PCB
-138
) and
2,2’,
3,4,4’
,5,5’-
hept
a-ch
lo ro
biph
enyl (P
CB-1
80)
Sper
m vo
lum
e, sper
m
conc
entra
tion
(sper
m
coun
t), o
vera
ll an
d pr
o-gr
essiv
e mot
ility an
d m
or-
phol
ogy
Age,
smok
ing,
absti
nenc
e tim
e, di
et,
Focu
sing o
n th
e sub
grou
p of m
en
with
nor
mal
sem
en q
ualit
y sho
wed
that
sper
m co
unt a
nd sp
erm
pro
-gr
essiv
e mot
ility
were
inve
rsely
re-
lated
to th
e con
cent
ratio
ns of
PCB
m
etab
olite
s with
in th
at gr
oup
[21]
ENvIRONMENTaL FaCTORs aND sEMEN QUaLITY R E v I E w P a P E R s
IJOMEH 2009;22(4) 311
Gre
enlan
d, S
wede
n, P
olan
d,
Ukr
aine
707 a
dult
male
s (1
93 In
uits
from
G
reen
land,
178 S
wedi
sh
fishe
rmen
, 141
men
from
W
arsa
w, P
olan
d,
and
195 m
en fr
om
Khar
kiv,
Ukr
aine)
Cros
s-sec
-tio
nal
Seru
m le
vels
of 2,
2’,4,4
’,5,5’
-hex
a-ch
loro
biph
enyl
(CB-
153)
, as a
pro
xy
of th
e tot
al PC
B bu
rden
, and
of
p,p
’-DD
E we
re d
eter
min
ed
Sper
m ch
rom
atin
stru
c-tu
re as
say (
SCSA
) was
us
ed to
asse
ss sp
erm
D
NA/ch
rom
atin
inte
grity
Life
style,
diet
, ab
stine
nce
Incr
easin
g DNA
frag
men
tatio
n in
dex w
ith in
crea
sing s
erum
leve
ls of
CB-
153 a
mon
g Eur
opea
n bu
t no
t Inu
it m
en, r
each
ing a
60%
hi
gher
aver
age l
evel
in th
e high
est
expo
sure
grou
p. N
o sig
nific
ant a
sso-
ciatio
ns w
ere f
ound
bet
ween
SCS
A-de
rived
par
amet
ers a
nd p
,p’-D
DE
seru
m co
ncen
tratio
ns
[22]
Gre
enlan
d, S
wede
n, P
olan
d,
Ukr
aine
763 m
en fr
om al
l reg
ions
in
Gre
enlan
d (n
= 19
4),
fishe
rmen
from
Swe
den
(n =
185)
, inha
bita
nts
of th
e city
of K
hark
iv,
Ukr
aine (
n =
195)
, and
in
habi
tant
s of t
he ci
ty of
W
arsa
w, P
olan
d (n
= 18
9)
Cros
s-sec
-tio
nal
Seru
m co
ncen
tratio
ns
of 2,
2′,4,
4′,5,
5′-h
exac
hlor
obip
heny
l (C
B-15
3) an
d 1,1
-dich
loro
-2,2-
bis
(p-ch
loro
phen
yl)-e
thyle
ne
(p,p
′-DD
E) w
ere e
xam
ined
Sper
m ch
rom
atin
stru
c-tu
re as
say (
SCSA
) was
us
ed to
asse
ss sp
erm
D
NA/ch
rom
atin
inte
grity
Life
style,
diet
, ab
stine
nce
Sper
m m
otili
ty wa
s inv
erse
ly re
lated
to
CB-
153 c
once
ntra
tion
in G
reen
-lan
d an
d th
e Swe
dish
fish
erm
en
popu
latio
n. A
cros
s all
4 reg
ions
, th
e spe
rm m
otili
ty de
crea
sed
on
aver
age b
y 3.6%
(95%
confi
denc
e in
terv
al =
1.7%
to 5.
6%) p
er o
ne-
unit
incr
ease
in th
e log
of b
lood
CB
-153
(ng/g
lipi
d). T
he co
ncen
tra-
tion
of p
,p′-D
DE
was n
egat
ively
asso
ciate
d wi
th sp
erm
mot
ility
in
the G
reen
landi
c pop
ulat
ion
and
in
the c
ompi
led d
atas
et
[23]
Swed
en
157 fi
sher
men
from
th
e coa
stal s
tretch
es o
f Sw
eden
, aged
27-6
7 yea
rs
Seru
m le
vels
of C
B-15
3 and
p’
p-D
DE we
re d
eter
min
ed.
Pros
tate
-spec
ific a
n-tig
en (P
SA),
neut
ral
α-glu
cosid
ase (
NAG
),
fructo
se an
d zin
c lev
els
Age, ab
stine
nce
time,
smok
ing
Ther
e was
a sig
nific
ant l
inea
r as-
socia
tion
betw
een
CB-1
53 an
d to
tal
amou
nt o
f PSA
. With
age, ab
sti-
nenc
e tim
e and
smok
ing i
nclu
ded
in
the m
odel
the a
ssocia
tion be
cam
e no
n-sig
nific
ant
[25]
Swed
en
176 S
wedi
sh fi
sher
men
(w
ith lo
w an
d hi
gh
cons
umpt
ion
of fa
tty fi
sh)
Seru
m le
vels
of 2,
2’,4,4
’,5,5’
-hex
a-ch
loro
biph
enyl
(CB-
153)
and
p,
p’-D
DE
were
exam
ined
Sper
m ch
rom
atin
stru
c-tu
re as
say (
SCSA
) was
us
ed to
asse
ss sp
erm
D
NA/ch
rom
atin
inte
grity
Life
style,
diet
, ab
stine
nce
A sig
nific
antly
lowe
r %D
FI w
as
foun
d in
the l
owes
t CB-
153 q
uin-
tile (
< 11
3 ng/g
lipi
d) co
mpa
red
with
the o
ther
qui
ntile
s; th
ere w
as
a sim
ilar t
ende
ncy,
altho
ugh
not
statis
ticall
y sign
ifica
nt, b
etwe
en
%D
FI an
d p,
p’-D
DE
[26]
R E v I E w P a P E R s J. JUREwICZ ET aL.
IJOMEH 2009;22(4)312
Stud
y pop
ulat
ion
Type
of s
tudy
Defi
nitio
n of
expo
sure
Sem
en an
alysis
Conf
ound
ers
Resu
ltsRe
fere
nces
Swed
en
305 y
oung
Swe
dish
m
en 18
-21 y
ears
old
from
th
e gen
eral
popu
latio
n
Seru
m le
vels
of 2,
2’,4,4
’,5,5’
-hex
a-ch
loro
biph
enyl
(CB-
153)
Sper
m co
ncen
tratio
n,
tota
l spe
rm co
unt,
sper
m
mot
ility
asse
ssed
man
u-all
y and
with
a co
mpu
ter-
aided
sper
m an
alyse
r (C
ASA)
, and
seru
m le
vels
of fo
llicle
-stim
ulat
ing h
or-
mon
e, in
hibi
n b,
testo
s-te
rone
, sex
ual h
orm
one-
bind
ing g
lobu
lin (S
HBG
), lu
tein
izing
hor
mon
e, an
d es
tradi
ol
Life
style,
diet
, ab
stine
nce
Nega
tive c
orre
latio
ns b
etwe
en
CB-1
53 le
vels,
testo
stero
ne
and
sper
m m
otili
ty
[27]
Tabl
e 3. E
xpos
ure t
o tri
halo
met
hane
(TH
M) a
nd se
men
qua
lity
Stud
y pop
ulat
ion
Type
of s
tudy
Defi
nitio
n of
expo
sure
Sem
en an
alysis
Conf
ound
ers
Resu
ltsRe
fere
nces
Uni
ted
Stat
es
228 f
ertil
e men
Coho
rt stu
dyW
ater
was
sam
pled
at
freq
uent
inte
rvals
(w
eekl
y or b
iwee
kly)
at
a re
pres
enta
tive
loca
tion
and
analy
sed
for
THM
4, H
AA9 a
nd T
OX
conc
entra
tions
that
wer
e in
deed
repr
esen
tativ
e of
the e
ntire
syste
m o
n th
at
day
Sper
m co
ncen
tratio
n,
coun
t, m
orph
olog
y, D
NA
inte
grity
, chr
omat
in
mat
urity
Age,
smok
ing,
alcoh
ol d
rinki
ng,
educ
atio
n lev
el,
seas
on, v
itam
in
inta
ke, c
offe
e dr
inki
ng, r
ace
No co
nsist
ent p
atte
rn w
as fo
und
of
incr
ease
d ab
norm
al se
men
qua
lity (
sper
m
conc
entra
tion
and
sper
m co
unt)
with
ele
vate
d ex
posu
re to
trih
alom
etha
nes
[34]
Uni
ted
Stat
es
157 h
ealth
y men
from
co
uples
with
out k
nown
ris
k fac
tor f
or in
ferti
lity
Cros
s-sec
tiona
lTo
tal T
HM
(TTH
M) l
evels
we
re as
signe
d ba
sed
on
wate
r util
ity m
easu
rem
ents
take
n du
ring t
he 90
day
s pr
eced
ing s
emen
colle
ction
Sper
m co
ncen
tratio
n,
sper
m co
unt,
volu
me,
mot
ility,
sper
m
mor
phol
ogy
Age,
smok
ing,
alcoh
ol d
rinki
ng,
educ
atio
n lev
el,
seas
on, c
offe
e dr
inki
ng
THM
leve
l was
not
asso
ciate
d wi
th
decr
emen
ts in
sem
en q
ualit
y. O
nly f
or
mot
ility,
a sm
all d
ecre
ase f
or ev
ery u
nit
incr
ease
in b
rom
odich
loro
met
hane
ex
posu
re le
vel w
as fo
und
[35]
Tabl
e 2. E
xpos
ure t
o or
gano
chlo
rine c
onta
min
ants,
dio
xins,
polyc
hlor
inat
ed b
iphe
nyls
and
sem
en q
ualit
y — co
nt.
ENvIRONMENTaL FaCTORs aND sEMEN QUaLITY R E v I E w P a P E R s
IJOMEH 2009;22(4) 313
methamidophos or endosulfan were conducted. In China, male workers at a large pesticide-manufacturing plant had an excess risk of aneuploidy and the risk of specific chro-mosome abnormalities: disomy for chromosome 18 and the three different types of sex chromosome disomy (XX, XY, YY) [39]. In the Mexico study, aneuploidies were found in 0.67% of total sperm nuclei. The authors concluded that exposure to organophosphates could inter-fere with sperm chromosome segregation and increase the risk of Turner’s syndrome [38]. The next study performed in Mexico showed the poorest semen quality among the subjects with the highest OP exposure and the highest uri-nary OP levels. Seasonal variations in sperm concentra-tion and sperm count were registered. The results showed a significant decrease in total sperm count among subjects with the highest exposure to OP [47] (Table 4). The first study which demonstrates links between specific biomarkers of environmental exposure to pesticides and biomarkers of male reproduction in humans was per-formed in United States [40]. Men with high exposure lev-el of alachlor (> 0.15 μg/g creatinine) had poorer semen parameters (concentration, percentage sperm with normal morphology, percentage motile sperm) than those less exposed. The exposure to herbicide 2,4-D, metolachlor and atrazine was associated with poorer sperm quality as well [40]. The next study where the exposure to carbaryl and chlorpyrifos was analysed by detecting the urinary metabolites showed an associated between exposure and lower sperm concentration and motility among men at-tending an infertility clinic [42] (Table 4). Yucra et al. [48] reported a significant reduction of semen volume and an increase in semen pH in men with organo-phosphate metabolites in urine in the study performed in Peru [48]. The poorest semen quality was found among farmers with the highest OP exposure and the highest uri-nary OP levels. The results showed a significant decrease in total sperm count among subjects with the highest ex-posure to OP [48] (Table 4). In summary, there are several indications that some pesticides may impair semen quality in humans, but weak exposure assessment in most studies precludes proper identification of responsible agents and evaluation of exposure-response relations.
exposure on sexual hormones were observed [39,43,44] (Table 4). However, this approach rarely provided any in-dications of cause-effect relationship.Among Danish greenhouse workers exposed to pesticides, the median values of sperm concentration and proportion of normal spermatozoa were lower by 60% and 14%, re-spectively, in the high- and low-level exposure groups. The median sperm concentration was lower by 40% for men with over 10 years’ work experience in a greenhouse than for those with experience below 5 years [43]. Also significantly lower sperm count was found in pesticide plant workers ex-posed to fenvalerate compared with non-exposed controls in the study performed in China [41] (Table 4). Some studies assessed the levels of reproductive hormones. Farmers exposed to pesticides in Argentina had higher se-rum oestradiol concentrations and lower luteinizing hor-mone (LH) concentrations than non-exposed men [45]. In Japan, pesticide sprayers had the serum testosterone con-centration in winter higher than the controls (p < 0.05), though luteinizing hormone and follicle stimulating hor-mone concentrations were not significantly different. The sperm counts and vitality were comparable between the groups, but detailed sperm motility analysis in summer re-vealed that the percentages of slow progressive and non-progressive motile sperm were twice as high in the sprayers (p < 0.05), and that of rapid progressive sperm tended to be lower (p = 0.06). Such differences were not observed in winter [46]. Semen quality and reproductive hormones across a spraying season were examined among Danish farmers (using and not using pesticides) and controls (non farmers) that were asked to give two semen samples [44]. The median sperm concentration declined significantly from the first to the second sample in both groups, but there was no statistical difference in the decline between the two groups. It was concluded that semen quality did not change across a spraying season as a result of pesticide exposure. Sprayers and non-sprayers had an equal decline in sperm concentration from the first to the second semen sample [44] (Table 4).In China and Mexico, studies of the prevalence of sperm aneuploidy [38,39] in agricultural workers exposed to organophosphorous pesticides like ethyl parathion,
R E v I E w P a P E R s J. JUREwICZ ET aL.
IJOMEH 2009;22(4)314
Tabl
e 4. E
xpos
ure t
o pe
sticid
es an
d se
men
qua
lity
Stud
y pop
ulat
ion
Type
of s
tudy
Defi
nitio
n of
expo
sure
Sem
en an
alysis
Conf
ound
ers
Resu
ltsRe
fere
nces
Haw
aii
46 m
en em
ploy
ed in
th
e pap
aya f
umiga
tion
indu
stry,
expo
sed
to
ethy
lene d
ibro
mid
e 43
non
-exp
osed
men
from
su
gar r
efine
ry
Cros
s-sec
tiona
lBa
sed
on jo
b tit
le ‘w
orke
rs wo
rkin
g in
prod
uctio
n of
pe
sticid
es’.
No b
iom
arke
r
Sper
m co
unt,
conc
entra
-tio
n, vi
abili
ty, m
otili
ty,
mor
phol
ogy
Life
style:
smok
-in
g, dr
inki
ngEx
posu
re to
pes
ticid
es si
gnifi
cant
ly de
-cr
ease
d sp
erm
coun
t per
ejac
ulat
e, th
e pe
rcen
tage
of v
iable
and
mot
ile sp
erm
. In
crea
se in
the p
ropo
rtion
of s
perm
with
sp
ecifi
c mor
phol
ogica
l abn
orm
alitie
s (ta
-pe
red
head
s, ab
sent
hea
ds an
d ab
norm
al ta
ils) w
as o
bser
ved
amon
g exp
osed
men
co
mpa
red
with
cont
rols.
No
effe
ct of
expo
-su
re to
ethy
lene d
ibro
mid
e on
sper
m ve
loc-
ity, t
he o
vera
ll pr
opor
tion
of sp
erm
with
no
rmal
mor
phol
ogy w
as o
bser
ved
[37]
Mex
ico
agric
ultu
ral w
orke
rs ex
pose
d to
pes
ticid
es
Cros
s-sec
tiona
lM
etab
olite
s of o
rgan
o-ph
osph
ate p
estic
ides
in
urin
e wer
e det
erm
ined
.
Sper
m co
ncen
tratio
n,
aneu
ploi
dyLi
festy
le: sm
ok-
ing,
drin
king
Expo
sure
to o
rgan
opho
spha
te p
estic
ides
wa
s asso
ciate
d wi
th sp
erm
hyp
erpl
oidy
/po
lyplo
idy.
Ther
e was
a sig
nific
ant a
sso-
ciatio
n be
twee
n th
e con
cent
ratio
n of
or-
gano
phos
phat
e met
abol
ites a
nd in
crea
sed
frequ
ency
of s
perm
aneu
ploi
dies
[38]
Chin
a 32
wor
kers
from
pes
ticid
e-m
anuf
actu
ring p
lant
43 w
orke
rs fro
m a
near
by
texti
le fa
ctory
free
of
pesti
cides
Cros
s-sec
tiona
lBa
sed
on jo
b tit
le ‘w
orke
rs m
anuf
actu
ring p
estic
ides
’.No
bio
mar
ker
Aneu
ploi
dy, m
otili
ty,
sper
m co
ncen
tratio
n, p
ro-
porti
on o
f spe
rm w
ith n
or-
mal
mor
phol
ogy
Age,
smok
ing,
alcoh
ol d
rinki
ng,
educ
atio
n lev
el,
seas
on, c
offe
e dr
inki
ng
Expo
sure
to o
rgan
opho
spha
te p
estic
ides
(p
arat
hion
, met
ham
idop
hos)
incr
ease
d th
e pre
valen
ce o
f spe
rm an
eupl
oidy
givin
g th
e rat
io o
f 1.56
(95%
CI:
1.06–
2.31)
. The
sp
ecifi
c chr
omos
ome a
bnor
mali
ties w
ere
diso
my f
or ch
rom
osom
e 18 a
nd th
e thr
ee
diffe
rent
type
s of s
ex ch
rom
osom
e diso
my
(XX,
XY,
YY)
.M
edian
sem
en p
aram
eter
s for
the e
xpos
ed
(and
non
-exp
osed
) men
wer
e as f
ollo
ws:
— p
ropo
rtion
of s
perm
with
nor
mal
mot
il-ity
— 50
.5% (6
1.3%
)—
pro
porti
on o
f spe
rm w
ith n
orm
al m
or-
phol
ogy —
59%
(61.5
%)
— sp
erm
conc
entra
tion
was l
ower
in th
e ex
pose
d gr
oup
com
pare
d wi
th th
e non
-ex
pose
d on
e
[39]
ENvIRONMENTaL FaCTORs aND sEMEN QUaLITY R E v I E w P a P E R s
IJOMEH 2009;22(4) 315
Uni
ted
Stat
es
50 m
en in
who
m al
l se
men
par
amet
ers
(con
cent
ratio
n,
perc
enta
ge sp
erm
with
no
rmal
mor
phol
ogy,
and
perc
enta
ge m
otile
sper
m)
were
low
(cas
es)
and
36 m
en in
who
m al
l se
men
par
amet
ers w
ere
with
in n
orm
al lim
its
(con
trols)
with
in M
issou
ri an
d M
inne
sota
Cros
s-sec
tiona
l M
etab
olite
s of e
ight
curre
nt-u
se p
estic
ides
in
urin
e: ala
chlo
r, 2,4
-D,
met
aloch
lor,
atra
zine,
diaz
inon
[2-is
opro
poxy
-4-
met
hyl-p
yrim
idin
ol
(IMPY
)], m
alath
ion,
ac
etoc
hlor
, DEE
T- (N
,N-
diet
hyl-m
-tolu
amid
e)
were
det
erm
ined
Case
s: all
sem
en p
aram
-et
ers (
conc
entra
tion,
pe
rcen
tage
sper
m w
ith
norm
al m
orph
olog
y, an
d pe
rcen
tage
mot
ile sp
erm
) we
re lo
wco
ntro
ls: al
l sem
en p
aram
-et
ers w
ere w
ithin
nor
mal
limits
Educ
atio
n lev
el,
seas
on, c
offe
e dr
inki
ng
Pesti
cide
met
abol
ite le
vels
were
el
evat
ed in
Miss
ouri
case
s, co
mpa
red
with
cont
rols,
for t
he h
erbi
cides
al
achl
or a
nd a
trazin
e an
d fo
r the
in
sect
icide
dia
zinon
[2-is
opro
poxy
-4-
met
hyl-p
yrim
idin
ol (I
MPY
)].
Men
from
Miss
ouri
with
hig
h le
vels
of a
lach
lor o
r IM
PY w
ere
signi
fican
tly m
ore
likel
y to
be
case
s tha
n we
re m
en w
ith lo
w le
vels.
The
her
bicid
es 2
,4-D
(2
,4-d
ichlo
roph
enox
yace
tic a
cid) a
nd
met
olac
hlor
wer
e al
so a
ssoc
iate
d wi
th p
oor s
emen
qua
lity i
n so
me
anal
yses
, whe
reas
ace
toch
lor
leve
ls we
re lo
wer i
n ca
ses t
han
in
cont
rols
(p =
0.0
4). N
o sig
nific
ant
asso
ciatio
ns w
ere
seen
for a
ny
pesti
cides
with
in M
inne
sota
, whe
re
leve
ls of
agr
icultu
ral p
estic
ides
wer
e lo
w, o
r for
the
inse
ct re
pella
nt D
EET
(N,N
-die
thyl-
m-to
luam
ide)
or t
he
mal
athi
on m
etab
olite
(mal
athi
on
dica
rbox
ylic a
cid)
[40]
Chin
a 32
male
wor
kers
who
were
expo
sed
to
fenv
alera
te an
d 46
male
ad
min
istra
tors
in th
e offi
ce
in th
e sam
e pes
ticid
e fa
ctory
Cros
s-sec
tiona
lTh
e am
ount
of f
enva
lerat
e in
indi
vidua
l sam
plin
g and
de
rmal
cont
amin
atio
n wa
s ev
aluat
ed
Sper
m co
ncen
tratio
n, m
o-til
ity, m
orph
olog
y, sp
erm
pr
ogre
ssion
, bea
t cro
ss fre
quen
cy
Age,
educ
atio
n,
smok
ing
Sper
m m
otio
n pa
ram
eter
s thr
ough
ro
utin
e se
men
ana
lysis
in th
e ex
posu
re g
roup
wer
e de
crea
sed
signi
fican
tly, a
nd th
e ab
norm
ality
ra
te o
f visc
idity
and
coag
ulat
ion
was
incr
ease
d sig
nific
antly
as c
ompa
red
with
the
inte
rnal
and
the
exte
rnal
co
ntro
l gro
ups.
Furth
erm
ore,
sper
m
prog
ress
ion
and
beat
cros
s fre
quen
cy
(BCF
) in
the
expo
sure
gro
up w
ere
also
sig
nific
antly
lowe
r tha
n th
ose
in th
e ex
tern
al co
ntro
l gro
up
[41]
R E v I E w P a P E R s J. JUREwICZ ET aL.
IJOMEH 2009;22(4)316
Stud
y pop
ulat
ion
Type
of s
tudy
Defi
nitio
n of
expo
sure
Sem
en an
alysis
Conf
ound
ers
Resu
ltsRe
fere
nces
Uni
ted
Stat
es
272 m
ales w
ere r
ecru
ited
thro
ugh
Mas
sach
uset
ts in
ferti
lity c
linic.
Urin
ary c
once
ntra
tions
of
1-na
phth
ol (1
N),
a met
abol
ite o
f car
-ba
ryl a
nd n
apht
halen
e, an
d 3,5
,6-tri
chlo
ro-2
-py
ridin
ol (T
CPY)
, a m
e-ta
bolit
e of c
hlor
pyrif
os
and
chlo
rpyr
ifos-m
ethy
l we
re d
eter
min
ed
Sper
m co
ncen
tratio
n,
perc
ent m
otile
sper
m, a
nd
perc
ent s
perm
with
nor
mal
mor
phol
ogy,
along
with
sp
erm
mot
ion
para
met
ers
Educ
atio
n, se
a-so
nalit
yFo
r inc
reas
ing 1
N te
rtiles
, adj
uste
d od
ds
ratio
s (O
Rs) w
ere s
ignifi
cant
ly ele
vate
d fo
r belo
w-re
fere
nce s
perm
conc
entra
-tio
n (O
R fo
r low
, med
ium
, and
high
ter-
tiles
= 1.
0, 4.2
, 4.2,
resp
ectiv
ely; p
-valu
e fo
r tre
nd =
0.01
) and
per
cent
mot
ile sp
erm
(1
.0, 2.
5, 2.4
; p-v
alue f
or tr
end
= 0.
01).
The
sper
m m
otio
n pa
ram
eter
mos
t stro
ngly
asso
ciate
d wi
th 1N
was
stra
ight-l
ine v
eloc-
ity. T
here
wer
e sug
gesti
ve, b
orde
rline
-sig-
nific
ant a
ssocia
tions
for T
CPY
with
sper
m
conc
entra
tion
and
mot
ility,
whe
reas
sper
m
mor
phol
ogy w
as w
eakl
y and
non
signi
fican
t-ly
asso
ciate
d wi
th b
oth
TCPY
and
1N
[42]
Den
mar
k 12
2 gre
enho
use w
orke
rs ex
pose
d to
pes
ticid
e: 44
with
low
expo
sure
65
with
med
ium
expo
sure
13
with
high
expo
sure
Cros
s-sec
tiona
lBa
sed
on jo
b tit
le ‘gr
een-
hous
e wor
kers
expo
sed
to
pesti
cides
’ with
: low
, me-
dium
and
high
expo
sure
No b
iom
arke
r
Sper
m co
ncen
tratio
n,
prop
ortio
n of
nor
mal
sper
-m
atoz
oa, v
iabili
ty, ve
locit
y, se
xual
horm
ones
Age,
educ
atio
n,
smok
ing
The m
edian
valu
es o
f spe
rm co
ncen
tratio
n an
d th
e con
cent
ratio
n an
d pr
opor
tion
of
norm
al sp
erm
atoz
oa w
ere 6
0% an
d 14
%
in th
e high
- and
low-
level
grou
ps, r
espe
c-tiv
ely. N
o di
ffere
nces
wer
e obs
erve
d fo
r the
via
bilit
y and
velo
city o
f spe
rm an
d se
xual
horm
ones
. The
med
ian sp
erm
conc
entra
-tio
n wa
s 40%
lowe
r for
the m
en w
ith >
10
year
s’ pe
riod
of w
ork i
n a g
reen
hous
e tha
n fo
r tho
se w
ith <
5 ye
ars’
perio
d
[43]
Den
mar
k 16
1 agr
icultu
ral w
orke
rs ex
pose
d to
pes
ticid
es
87 ag
ricul
tura
l wor
kers
not
usin
g pes
ticid
es
Cros
s-sec
tiona
lBa
sed
on jo
b tit
le ‘ag
ri-cu
ltura
l wor
kers
usin
g pe
sticid
es’
No b
iom
arke
r
Sper
m m
orph
olog
y, vi-
talit
y, m
otili
ty, sp
erm
ch
rom
atin
den
atur
atio
n (S
CSA)
and
repr
oduc
tive
horm
ones
Age,
educ
atio
n,
smok
ing
The m
edian
sper
m co
ncen
tratio
n de
cline
d sig
nific
antly
from
the fi
rst to
the s
econ
d sa
mpl
e for
the m
en sp
rayin
g pes
ticid
es an
d th
e men
not
spra
ying p
estic
ides
, but
ther
e wa
s no
statis
tical
diffe
renc
e in
the d
eclin
e be
twee
n th
e two
grou
ps. O
nly m
inor
chan
g-es
wer
e fou
nd in
the s
perm
mor
phol
ogy,
vitali
ty, m
otili
ty, sp
erm
chro
mat
in d
enat
ur-
atio
n (S
CSA)
and
repr
oduc
tive h
orm
ones
[44]
Tabl
e 4. E
xpos
ure t
o pe
sticid
es an
d se
men
qua
lity —
cont
.
ENvIRONMENTaL FaCTORs aND sEMEN QUaLITY R E v I E w P a P E R s
IJOMEH 2009;22(4) 317
Arge
ntin
a 22
5 male
par
tner
s fro
m
cons
ecut
ively
recr
uite
d co
uples
, who
had
their
fir
st in
ferti
lity c
onsu
ltatio
n be
twee
n 19
95 an
d 19
98
Cros
s-sec
tiona
lBa
sed
on jo
b tit
le “f
arm
ers”
No b
iom
arke
r
Sper
m co
ncen
tratio
n,
sper
m m
otili
ty,
mor
phol
ogy,
repr
oduc
tive
horm
ones
Educ
atio
n,
seas
onali
tyM
en ex
pose
d to
pes
ticid
es h
ad h
igher
se
rum
oes
tradi
ol co
ncen
tratio
ns, a
nd
thos
e exp
osed
to so
lvent
s had
lowe
r LH
co
ncen
tratio
ns th
an n
on-e
xpos
ed m
en
[45]
Japa
n 18
male
pes
ticid
e spr
ayer
s ou
t of 5
4 wor
king
for 9
co
mpa
nies
in ce
ntra
l Ja
pan
and
18 ag
e-m
atch
ed
stude
nts
Cros
s-sec
tiona
lBa
sed
on jo
b tit
le “p
estic
ide s
pray
er”
No b
iom
arke
r
Sper
m co
ncen
tratio
n,
sper
m m
otili
ty,
mor
phol
ogy,
repr
oduc
tive
horm
ones
Age,
smok
ing,
alcoh
ol d
rinki
ng,
educ
atio
n lev
el
Seru
m te
stoste
rone
conc
entra
tion
in
wint
er in
the s
pray
ers w
as h
igher
than
in
the c
ontro
ls (p
< 0.
05),
thou
gh lu
tein
izing
ho
rmon
e and
folli
cle st
imul
atin
g hor
mon
e co
ncen
tratio
ns w
ere n
ot si
gnifi
cant
ly di
ffere
nt. S
perm
coun
ts an
d vit
ality
were
co
mpa
rabl
e bet
ween
the g
roup
s, bu
t de
taile
d sp
erm
mot
ility
analy
sis in
sum
mer
re
veale
d th
at th
e per
cent
ages
of s
low
prog
ressi
ve an
d no
npro
gres
sive m
otile
sp
erm
wer
e twi
ce as
high
in th
e spr
ayer
s (p
< 0.
05),
and
that
of r
apid
pro
gres
sive
sper
m te
nded
to b
e low
er (p
= 0.
06).
Such
di
ffere
nces
wer
e not
obs
erve
d in
win
ter
[46]
Mex
ico
52 vo
lunt
eers
Long
itudi
nal
follo
w-up
stud
yU
rinar
y org
anop
hosp
hate
m
etab
oliti
esEd
ucat
ion
level,
se
ason
The r
esul
ts re
veale
d th
at th
e poo
rest
sem
en
quali
ty wa
s fou
nd am
ong t
he su
bjec
ts wi
th
the h
ighes
t OP
expo
sure
and
the h
ighes
t ur
inar
y OP
levels
. Sea
sona
l var
iatio
ns in
sp
erm
conc
entra
tion
and
sper
m co
unt w
ere
regis
tere
d. T
he re
sults
show
ed a
signi
fican
t de
crea
se in
tota
l spe
rm co
unt a
mon
g su
bjec
ts wi
th th
e high
est e
xpos
ure t
o O
P
[47]
Peru
31
pes
ticid
e ap
plica
tors
expo
sed
to
orga
noph
osph
ate (
OP)
pe
sticid
es an
d 31
non
-ex
pose
d we
re re
crui
ted
(age
, 20–
60 ye
ars)
Cros
s-sec
tiona
l U
rinar
y lev
els o
f OP
me-
tabo
lites
(dim
ethy
l and
di
ethy
l pho
spha
tes a
nd
thio
phos
phat
es)
Sper
m co
ncen
tratio
n,
perc
enta
ge o
f spe
rm m
otil-
ity, p
erce
ntag
e of n
orm
al m
orph
olog
y, se
men
leuc
o-cy
tes a
nd co
ncen
tratio
ns o
f fru
ctose
and
zinc
Age,
smok
ing,
alcoh
ol d
rinki
ng,
educ
atio
n lev
el
Sem
en an
alysis
reve
aled
a sign
ifica
nt re
-du
ction
of s
emen
volu
me a
nd an
incr
ease
in
sem
en p
H in
men
with
OP
met
abol
ites.
Mul
tiple
regr
essio
n an
alysis
show
ed th
at
both
occ
upat
iona
l exp
osur
e to
pesti
cides
an
d th
e tim
e of e
xpos
ure t
o pe
sticid
es w
ere
mor
e clo
sely
relat
ed to
alte
ratio
ns in
sem
en
quali
ty pa
ram
eter
s tha
n th
e sin
gle m
ea-
sure
men
t of O
P m
etab
olite
s in
urin
e
[48]
R E v I E w P a P E R s J. JUREwICZ ET aL.
IJOMEH 2009;22(4)318
Tabl
e 5. E
xpos
ure t
o ph
thala
tes a
nd se
men
qua
lity
Stud
y pop
ulat
ion
Type
of s
tudy
Defi
nitio
n of
expo
sure
Sem
en an
alysis
Conf
ound
ers
Resu
ltsRe
fere
nces
Uni
ted S
tate
s 16
8 men
who
wer
e par
t of
subf
ertil
e cou
ples
and w
ho
pres
ente
d to M
assa
chus
etts
Gen
eral
Hos
pita
l an
drol
ogy l
abor
ator
y for
se
men
analy
sis be
twee
n Ja
nuar
y 200
0 and
Ap
ril 20
01
Cros
s-sec
tiona
lEi
ght p
htha
late
met
abol
ites w
ere
mea
sure
d
Sper
m co
ncen
tratio
n,
mot
ility,
mor
phol
ogy
Age,
absti
nenc
e tim
e, an
d sm
okin
g sta
tus
A do
se-re
spon
se re
latio
n be
twee
n te
rtiles
of m
ono-
butyl
pht
halat
e and
sp
erm
mot
ility
and
sper
m co
ncen
tratio
n wa
s obs
erve
d. In
addi
tion,
ther
e was
a d
ose-
resp
onse
relat
ion
betw
een
terti
les
of m
ono-
benz
yl ph
thala
te an
d sp
erm
co
ncen
tratio
n
[53]
Uni
ted
Stat
es
295 m
ale p
artn
ers o
f su
bfer
tile c
oupl
es w
ho
pres
ente
d fo
r sem
en
analy
sis to
Mas
sach
uset
ts G
ener
al H
ospi
tal
betw
een
1999
and
2003
Cros
s-sec
tiona
lSe
lecte
d ph
thala
te
met
abol
ites w
ere
mea
sure
d in
urin
e
Sexu
al ho
rmon
esEd
ucat
iona
l lev
el,
age,
absti
nenc
e tim
e, sm
okin
g sta
tus
An in
terq
uarti
le ra
nge (
IQR)
chan
ge
in m
onob
enzy
l pht
halat
e (M
BzP)
ex
posu
re w
as si
gnifi
cant
ly as
socia
ted
with
a 1
0% d
ecre
ase i
n FS
H co
ncen
tratio
n.
Addi
tiona
lly, a
n IQ
R ch
ange
in
mon
obut
yl ph
thala
te (M
BP) e
xpos
ure
was a
ssocia
ted
with
a 4.8
% in
crea
se
in in
hibi
n B
but t
his w
as o
f bor
derli
ne
signi
fican
ce
[54]
Uni
ted St
ates
463 m
ales i
n sub
ferti
le co
uples
who
pres
ented
fo
r sem
en an
alysis
to
Mas
sach
usett
s Gen
eral
Hos
pital
betw
een
Janu
ary 2
000 a
nd M
ay 20
04
Cros
s-sec
tiona
lEi
ght p
htha
late
met
abol
ites w
ere
mea
sure
d
Sper
m co
ncen
tratio
n,
mot
ility,
mor
phol
ogy
Age,
absti
nenc
e tim
e, sm
okin
g sta
tus
Ther
e wer
e dos
e-re
spon
se re
latio
nshi
ps
of m
ono-
butyl
pht
halat
e (M
BP) w
ith lo
w sp
erm
conc
entra
tion
and
mot
ility.
The
re
was s
ugge
stive
evid
ence
of a
n as
socia
tion
betw
een
the h
ighes
t mon
o-be
nzyl
phth
alate
(MBz
P) q
uarti
le an
d lo
w sp
erm
co
ncen
tratio
n
[55]
Swed
en
234 y
oung
Swe
dish
men
Cros
s-sec
tiona
lU
rinar
y con
cent
ratio
ns
of p
htha
late m
etab
olite
s we
re d
eter
min
ed
Sem
en vo
lum
e, sp
erm
co
ncen
tratio
n an
d m
otili
ty we
re m
easu
red,
toge
ther
wi
th sp
erm
chro
mat
in
inte
grity
(spe
rm ch
rom
atin
str
uctu
re as
say)
and
bioc
hem
ical m
arke
rs of
ep
idid
ymal
and
pros
tatic
fu
nctio
n, re
prod
uctiv
e ho
rmon
es in
seru
m
Educ
atio
n lev
el,
age,
absti
nenc
e tim
e, sm
okin
g sta
tus
Subj
ects
with
in th
e high
est q
uarti
le fo
r m
onoe
thyl
phth
alate
(MEP
) had
fewe
r m
otile
sper
m, m
ore i
mm
otile
sper
ms,
and
lowe
r lut
einizi
ng h
orm
one v
alues
, but
th
ere w
as n
o su
gges
tion
of h
arm
ful e
ffects
fo
r mos
t oth
er en
dpoi
nts
[56]
ENvIRONMENTaL FaCTORs aND sEMEN QUaLITY R E v I E w P a P E R s
IJOMEH 2009;22(4) 319
Uni
ted
Stat
es
Male
s (N
= 45
) of
subf
ertil
e cou
ples
pr
esen
ting t
o M
ichiga
n in
ferti
lity c
linic
Cros
s-sec
tiona
l pi
lot s
tudy
Urin
ary c
once
ntra
tions
of
pht
halat
e met
abol
ites
were
mea
sure
d
Mot
ility,
conc
entra
tion,
m
orph
olog
yEd
ucat
ion
level,
ag
e, ab
stine
nce
time
Low
sper
m co
ncen
tratio
n wa
s sig
nific
antly
asso
ciate
d wi
th el
evat
ed
med
ian co
ncen
tratio
ns o
f mon
oeth
yl ph
thala
te (M
EP) a
nd lo
w m
orph
olog
y wi
th el
evat
ed m
edian
conc
entra
tions
of
mon
o-3-
carb
oxyp
ropy
l ph
thala
te. I
ncre
ased
odd
s for
low
conc
entra
tion
and
eleva
ted
med
ian
conc
entra
tions
of m
etab
olite
s of
di(2
-eth
ylhex
yl) p
htha
late (
DEH
P)
(OR
= 5.
4, 95
% C
I: 0.9
–30.8
) an
d lo
w m
orph
olog
y and
elev
ated
m
edian
conc
entra
tions
of M
EP
(OR
= 3.
4, 95
% C
I: 0.9
–13.8
) wer
e als
o fo
und
[57]
Indi
a The s
tudy
was
cond
ucte
d in
the u
rban
/rura
l po
pulat
ion
of L
uckn
ow
visiti
ng O
bste
trics
and
Gyn
ecol
ogy D
epar
tmen
t
Cros
s-sec
tiona
lU
rinar
y con
cent
ratio
ns
of p
htha
late m
etab
olite
s we
re m
easu
red
Mot
ility,
conc
entra
tion,
m
orph
olog
yAg
e, ab
stine
nce
time,
smok
ing
statu
s
Infe
rtile
men
show
ed st
atist
ically
sig
nific
ant (
p <
0.05
) high
er le
vels
of
pollu
tant
s in
the s
emen
than
ferti
le m
en. A
neg
ative
corre
latio
n be
twee
n se
men
pht
halat
e lev
el viz
DEH
P an
d sp
erm
qua
lity a
nd p
ositi
ve as
socia
tion
with
dep
olar
ised
mito
chon
dria,
ele
vatio
n in
RO
S pr
oduc
tion
and
LPO
, DNA
frag
men
tatio
n wa
s es
tabl
ished
[58]
Chin
a Pa
rticip
ants
resid
ing i
n Sh
angh
ai we
re su
rvey
ed
in 20
02. S
emen
spec
ies
of 52
men
(age
d fro
m 23
to
48 ye
ars)
were
colle
cted
from
out
patie
nts o
f Sh
angh
ai In
stitu
te o
f Pl
anne
d Pa
rent
hood
Re
sear
ch
Cros
s-sec
tiona
lCo
ncen
tratio
ns o
f thr
ee
kind
s of c
omm
only
used
ph
thala
tes (
di-e
thyl
phth
alate
, DEP
; di-n
-bu
tyl p
htha
late,
DBP
; di
-2-e
thylh
exyl
phth
alate
, D
EHP
Sper
m d
ensit
y, via
bilit
y, co
ncen
tratio
nTh
ere w
as a
signi
fican
t pos
itive
as
socia
tion
betw
een
lique
fied
time o
f se
men
and
phth
alate
conc
entra
tions
of
sem
en. T
here
was
no
signi
fican
t di
ffere
nce b
etwe
en p
htha
late
conc
entra
tions
of s
emen
and
sper
m
dens
ity o
r viab
ility
[59]
R E v I E w P a P E R s J. JUREwICZ ET aL.
IJOMEH 2009;22(4)320
level (DEHP) and sperm concentration, motility, % of abnormal sperm was found in a population of men that visited an infertility clinic [58].Another study performed by Duty and co-workers [54] to explore the association between environmental levels of phthalates and altered reproductive hormone levels in adult men showed that an interquartile range (IQR) change in monobenzyl phthalate (MBzP) exposure was significantly associated with a 10% decrease in follicle-stimulating hormone (FSH) concentration. Additionally, an IQR change in monobutyl phthalate (MBP) exposure was associated with a 4.8% increase in inhibin B, but this was of borderline significance [54].On other hand, in a Swedish study, Jonsson et al. (2005) [56] reported that only subjects within the highest quartile for monoethyl phthalate (MEP) had fewer mo-tile sperms, more immotile sperms, and lower luteinizing hormone values, but there was no suggestion of harmful effects for most other endpoints. In the study in China there was no significant difference between phthalate concentrations of semen and sperm density and liveabil-ity, while there was a significant positive association be-tween liquefied time of semen and phthalate concentra-tions of semen [59]. Summing up, results of few studies of subfertile men dem-onstrate associations between phthalate levels commonly experienced by the public and impaired sperm quality (impact on sperm concentration, morphology, motility), but findings have not been corroborated in studies of men from the general population. Effects of phthalates in sexu-ally mature rodents have only been seen at much higher exposures levels but perhaps the human male is more sus-ceptible to the class of chemicals. It remains to be investi-gated if maternal exposures to phthalates have bearings as to semen quality in the offspring.
Mobile phones
There has been a tremendous increase in the use of mo-bile phones in the past decade and concerns are growing about the possible detrimental effects of high-frequency electromagnetic fields (EMF) emitted by these devices on
PhthalatesPhthalates are among the most widely used man-made chemicals released to the environment over the last sev-eral decades [49]. Phthalates are used as plasticizers to increase the flexibility of PCV products like: toys, vinyl flooring and electricity cables or medical devices. The main plasticizer used in PVC based medical devices is di(2-ethylhexyl) phthalate (DEHP). Phthalates are also used as solvents or fixing agents in perfumes, body lotions and other cosmetics. Humans are mainly exposed to these compounds through the diet, medical devices and consum-er products. In spite of short half times in the organism, the compounds or their metabolites have been detected in urine in more than 95% of men and women that have been investigated [50]. There are numerous animal studies on the risk of infer-tility related to phthalates exposure. Laboratory experi-ments with rodents have shown repeatedly that phthalate at very high doses (g/kg in gavage range) can adversely af-fect sperm quality. Ge et al. (2007) [51] found that at lower doses phthalates increase testosterone production either by increasing Leyding cell numbers or by directly stimulat-ing testosterone production [51]. However, inhibition of testosterone was noticed in both foetal and adult Leyding cells when rats were exposed to higher doses [51]. Other studies in animals showed reduction of protein levels in foetal Leyding cells and deregulation of cholesterol trans-port and steroid synthesis [52]. Several recent epidemiological studies have addressed the male reproductive toxicity of phthalates [53–59] (Table 5). Duty et al. (2003) [53] compared levels of eight phthalate metabolites in urine among men with normal and abnor-mal semen quality recruited from 168 subfertile couples. They observed an inverse dose-response relationship be-tween 2 phthalate metabolites (monobutyl- and monoben-zyl phthalate (MBP, MbzP)) on the one side and sperm concentration and motility on the other. These findings were corroborated in a subsequent study of 463 infertile men using same study design [55] and to some extent by a smaller study including 45 infertility clients from the Great Lakes Region in US [57]. Also in a study performed in India, a negative correlation between semen phthalate
ENvIRONMENTaL FaCTORs aND sEMEN QUaLITY R E v I E w P a P E R s
IJOMEH 2009;22(4) 321
In the study performed in Poland, 304 males attending an infertility clinic were divided into three groups: 99 pa-tients who did not use mobile phones, 157 males who had used GSM equipment sporadically for the period of 1–2 years, 48 patients who had been regularly using mo-bile phones for more than 2 years. In the analysis of the effect of GSM equipment on the semen, an increase was noted in the percentage of sperm cells of abnormal mor-phology with the duration of exposure to GSM phone [66] (Table 6).The results of the presented studies provide limited sup-port to the hypothesis that use of mobile phones may ad-versely affect semen quality, but most of the presented studies are small [60–63] only three [64–66] were conduct-ed on the sample of about 300 men. So there is a need for future studies in this area.
DISCUSSION
The results of the reviewed studies suggest that expo-sure to environmental factors (air pollution, pesticides, phthalates, PCB and the use of mobile phones) may af-fect semen quality. However, when reviewing the epi-demiological studies on the influence of environmental hazards on semen quality, it is important to take into ac-count the current limitations of these studies resulting from inadequacies in semen analysis, exposure evalua-tion and design of studies. The studies conducted in the general population are very rare mainly because of the difficulties in collecting the semen samples. The fact that most of the studies are drawn from infertility clin-ics may introduce a selection bias. Some of the subjects are classified as fertile; they belong to a population of men seeking medical care, which is probably different from the general population in terms of other exposure factors, because these men are more health-concerned and therefore less exposed to other agents such as alco-hol or drugs. In addition, subjects may underreport their lifestyle habits, especially for smoking and drinking, thus biasing the results. Another possible variable that needs to be considered is the simultaneous presence of other exposure factors. In reviewed studies authors collected
human health. Although many studies have recently been published on this topic, the effects of the EMF emitted by cell phones on living cells and organs are still unclear. Here we review the few studies addressing possible effects of cellular phone usage on human semen quality. In a small prospective study involving 13 men with nor-mal sperm, GSM phone usage in 5 days for 6 hours per day decreased the rapid progressive motility of sperm [60] (Table 6). Interesting results were obtained in a pilot study performed in Australia; men who carried their mobile phone in their hip pocket or on their belt had lower sperm motility than men who did not carry a mobile phone or who carried their mobile phone elsewhere on the body [61]. There are also two small studies where semen sample was exposed to cellular phone radiation [62,63] (Table 6). The first study was performed in Turkey where statisti-cally significant changes were observed in the rapid pro-gressive, slow progressive and no-motility categories of sperm movement. Electromagnetic radiation (EMR) ex-Electromagnetic radiation (EMR) ex- (EMR) ex-posure caused a subtle decrease in the rapid progressive and slow progressive sperm movement. It also caused an increase in the no-motility category of sperm move-ment. There was no statistically significant difference in the sperm concentration between two groups [62]. The second study was performed in United States where sam-ples exposed to radiofrequency electromagnetic waves (RF-EMW) showed a significant decrease in sperm mo-tility and viability, increase in reactive oxygen species (ROS) level, and decrease in ROS-TAC (Total Antioxi-dant Capacity) score. Levels of TAC and DNA damage showed no significant differences from the non-exposed group [63]. A recent study involving 361 men attending an infer-tility clinic suggested that use of cell phones for lon-ger durations adversely affected the quality of semen by decreasing the sperm counts, motility, viability and morphology [64]. In Hungary a study was performed among 371 male patients of infertility clinics. The dura-tion of mobile phone use was correlated negatively with the proportion of rapid progressive motile sperm, and positively with the proportion of slow progressive motile sperm [65] (Table 6).
R E v I E w P a P E R s J. JUREwICZ ET aL.
IJOMEH 2009;22(4)322
Tabl
e 6. M
obile
pho
nes a
nd se
men
qua
lity
Stud
y pop
ulat
ion
Type
of s
tudy
Defi
nitio
n of
expo
sure
Sem
en an
alysis
Conf
ound
ers
Resu
ltsRe
fere
nces
Uni
ted
Stat
es
361 m
en u
nder
goin
g in
ferti
lity e
valu
atio
n
Cros
s-sec
tiona
lFo
ur gr
oups
acco
rdin
g to
their
ac
tive c
ell p
hone
use
: gr
oup
A: n
o us
e;
grou
p B:
< 2
h/da
y;gr
oup
C: 2–
4 h/d
ay;
grou
p D
: > 4
h/da
y
Sper
m p
aram
eter
s (v
olum
e, liq
uefa
ction
tim
e, pH
, visc
osity
, sp
erm
coun
t,
mot
ility,
viab
ility,
an
d m
orph
olog
y)
Cont
rolli
ng fo
r lif
estyl
e fac
tors,
ed
ucat
ion
level
The c
ompa
rison
s of m
ean s
perm
co
unt,
mot
ility,
viab
ility,
and n
orm
al m
orph
olog
y am
ong f
our d
iffer
ent c
ell
phon
e use
r gro
ups s
howe
d sta
tistic
ally
signi
fican
t diff
eren
ces.
Mea
n spe
rm
mot
ility,
viab
ility,
and n
orm
al m
orph
olog
y wer
e sign
ifica
ntly
diffe
rent
in
cell p
hone
user
grou
ps w
ithin
two s
perm
co
unt g
roup
s. Th
e lab
orat
ory v
alues
of
the a
bove
four
sper
m pa
ram
eter
s de
crea
sed i
n all f
our c
ell ph
one u
ser
grou
ps as
the d
urat
ion o
f dail
y exp
osur
e to
cell p
hone
s inc
reas
ed
[64]
Hun
gary
37
1 male
s fro
m in
ferti
lity c
linic
Cros
s-sec
tiona
lG
roup
1 wa
s sub
divid
ed in
to
thos
e who
use
d a c
ell p
hone
fo
r les
s tha
n 15
min
/day
(low
trans
mitt
ers)
and
thos
e wh
o u
sed
it fo
r ove
r 60 m
in/d
ay
(high
tran
smitt
ers).
G
roup
2 wa
s sub
divid
ed in
to
thos
e pat
ients
who
kept
their
cell
phon
e in
the s
tand
by p
ositi
onwi
thin
a di
stanc
e of 5
0 cm
for
less t
han
1 h d
aily (
shor
t-sta
ndby
gr
oup)
and
thos
e who
kept
their
cell
phon
e in
the s
tand
by
posit
ion
with
in a
dista
nce
of 50
cm fo
r mor
e tha
n 20
h
daily
(lon
g-sta
ndby
grou
p)
Sper
m co
ncen
tratio
n,
mot
ility,
mor
phol
ogy,
volu
me,
coun
t
Cont
rolli
ng fo
r lif
estyl
e fac
tors
The d
urat
ion
of p
osse
ssion
and
the d
aily
trans
miss
ion
time c
orre
lated
neg
ative
ly wi
th th
e pro
porti
on o
f rap
id p
rogr
essiv
e m
otile
sper
m an
d po
sitive
ly wi
th th
e pr
opor
tion
of sl
ow p
rogr
essiv
e mot
ile
sper
m. T
he lo
w an
d hi
gh tr
ansm
itter
gr
oups
also
diff
ered
in th
e pro
porti
on
of ra
pid
prog
ressi
ve m
otile
sper
m. T
he
prol
onge
d us
e of c
ell p
hone
s may
hav
e ad
verse
effe
cts o
n th
e spe
rm m
otili
ty ch
arac
teris
tics
[65]
Ger
man
y 13
men
wi
th n
orm
al sp
erm
Pros
pecti
ve
study
GSM
pho
ne u
sage
5 d
ays/w
eek,
6 h/d
aySp
erm
conc
entra
tion,
m
otili
ty, m
orph
olog
y, vo
lum
e, co
unt
Cont
rolli
ng fo
r lif
estyl
e fac
tors
A re
ducti
on in
the r
apid
pro
gres
sive
mot
ility
of sp
erm
[60]
ENvIRONMENTaL FaCTORs aND sEMEN QUaLITY R E v I E w P a P E R s
IJOMEH 2009;22(4) 323
Austr
alia
52 m
en b
etwe
en th
e ag
es o
f 18 a
nd 35
year
s fro
m th
e cam
pus o
f the
U
nive
rsity
of W
este
rn
Austr
alia
Perc
enta
ge o
f mot
ile
sper
m an
d th
e num
ber
of sp
erm
per
ml o
f eja
culat
e
Cont
rolli
ng fo
r lif
estyl
e fac
tors
Inte
resti
ngly,
men
who
carri
ed th
eir
mob
ile p
hone
in th
eir h
ip p
ocke
t or o
n th
eir b
elt h
ad lo
wer s
perm
mot
ility
than
m
en w
ho d
id n
ot ca
rry a
mob
ile p
hone
or
who
carri
ed th
eir m
obile
pho
ne el
sewh
ere
on th
e bod
y
[61]
Turk
ey
27 m
ales
The s
emen
sam
ple o
btain
ed
from
each
par
ticip
ant w
as
divid
ed eq
ually
into
two
parts
. O
ne o
f the
spec
imen
s was
ex
pose
d to
EM
R em
itted
by
an ac
tivat
ed 90
0 MH
z cell
ular
ph
one,
wher
eas t
he o
ther
was
no
t
Sper
m co
ncen
tratio
n,
mot
ility,
mor
phol
ogy,
volu
me,
coun
t
Cont
rolli
ng fo
r lif
estyl
e fac
tors
Stat
istica
lly si
gnifi
cant
chan
ges w
ere
obse
rved
in th
e rap
id p
rogr
essiv
e, slo
w pr
ogre
ssive
and
no-m
otili
ty ca
tego
ries o
f sp
erm
mov
emen
t. EM
R ex
posu
re ca
used
a s
ubtle
dec
reas
e in
the r
apid
pro
gres
sive
and
slow
prog
ressi
ve sp
erm
mov
emen
t. It
also
caus
ed an
incr
ease
in th
e no-
mot
ility
cate
gory
of s
perm
mov
emen
t. Th
ere w
as
no st
atist
ically
sign
ifica
nt d
iffer
ence
in
sper
m co
ncen
tratio
n be
twee
n tw
o gr
oups
.
[62]
Uni
ted
Stat
es
healt
hy d
onor
s (n
= 23
) an
d in
ferti
le pa
tient
s (n
= 9)
Pros
pecti
ve
pilo
t stu
dyAf
ter l
ique
facti
on, n
eat s
emen
sa
mpl
es w
ere d
ivide
d in
to
two
aliqu
ots.
One
aliq
uot
(exp
erim
enta
l) fro
m ea
ch
patie
nt w
as ex
pose
d
to ce
llular
pho
ne ra
diat
ion
(in ta
lk m
ode)
for 1
h, a
nd th
e se
cond
aliq
uot (
non-
expo
sed)
se
rved
as th
e con
trol
sam
ple u
nder
iden
tical
cond
ition
s
Evalu
atio
n of
sper
m
para
met
ers (
mot
ility,
via
bilit
y), r
eacti
ve
oxyg
en sp
ecies
(RO
S),
tota
l ant
ioxid
ant
capa
city (
TAC)
of
sem
en, R
OS-T
AC
scor
e, an
d sp
erm
D
NA d
amag
e
Cont
rolli
ng fo
r lif
estyl
e fac
tors
Sam
ples
expo
sed
to R
F-EM
W sh
owed
a s
ignifi
cant
dec
reas
e in
sper
m m
otili
ty an
d via
bilit
y, in
crea
se in
RO
S lev
el, an
d de
crea
se in
RO
S-TAC
scor
e. Le
vels
of T
AC an
d D
NA d
amag
e sho
wed
no
signi
fican
t diff
eren
ces f
rom
the n
on-
expo
sed
grou
p
[63]
Polan
d 30
4 male
s Cr
oss-s
ectio
nal
Gro
up A
: 99 p
atien
ts wh
o di
d no
t use
mob
ile p
hone
s, G
roup
B:
157 m
ales w
ho h
ave u
sed
GSM
equi
pmen
t spo
radi
cally
fo
r the
per
iod
of 1–
2 yea
rs, an
d G
roup
C: 4
8 peo
ple w
ho h
ave
been
regu
larly
usin
g mob
ile
phon
e for
mor
e tha
n 2 y
ears
Sper
m co
ncen
tratio
n,
mot
ility,
mor
phol
ogy,
volu
me,
coun
t
Cont
rolli
ng fo
r lif
estyl
e fac
tors,
ag
e, pl
ace o
f re
siden
ce
In th
e ana
lysis
of th
e effe
ct of
GSM
eq
uipm
ent o
n th
e sem
en it
was
not
ed th
at
an in
crea
se in
the p
erce
ntag
e of a
bnor
mal
mor
phol
ogy s
perm
cells
was
asso
ciate
d wi
th th
e dur
atio
n of
expo
sure
to th
e wav
es
emitt
ed b
y the
GSM
pho
ne
[66]
R E v I E w P a P E R s J. JUREwICZ ET aL.
IJOMEH 2009;22(4)324
Exposure assessmentExposure assessment is a crucial part of any area of envi-ronmental epidemiology. The best assessment of exposure usually provide measurements of contaminants in ambient air samples, or in blood, urine, semen or other biological specimens that might be appropriate. Exposure in several of the presented studies was based on specific biomarkers of exposure or the assessment of expo-sure was performed. Phthalates were assessed in urine, air pollution measurement was also taken. However, in the studies on pesticide exposure and semen quality the expo-sure was based in almost all studies on the job titles. Only Swan et al. and Yucra et al. [40,48] used specific biomark-ers of pesticide exposure [40,48]. It is well known that mis-classification of exposure may occur if the type of exposure is based solely on subject’s memory.Biological assessment of exposure is the most precise indi-cator, but sometimes it can be limited by the cost and the large number of suspected chemicals that individuals were exposed to, what usually is the case in relation to pesti-cides exposure.It is not only the type of exposure but also the timing in relation to the development of the reproductive system that is important for the assessment of type and magni-tude of the harmful effect. The period between the 8th and the 10th gestational week seems to be critical for the development of male gonads [70]. It has been hy-pothesised that even relatively insignificant exposures acting at this period of prenatal life may have serious consequences for the future reproductive capability of men [5]. So the studies of environmental effects on male reproduction should not only focus on exposures during the reproductive life, but should also include the foetal periods of male reproductive system devel-opment.
Type of study designWith few exceptions, all studies comparing the distribu-tions of seminal variables in an exposed populations with those of an non-exposed reference population were cross-sectional. The participation rate was about 40–60% and there was tendency towards lower participation rates
information on age, alcohol and coffee drinking, tobacco smoking, occupational exposure, and conducted a multi-variate analysis.Sometimes, like in case of trihalomethanes [34,35] or mo-bile phones [63–66] there are just a few studies so it is dif-ficult to reach the conclusion. The next problem is also the size of study population. In case of PCBs there are lots of small pilot studies [19–21] but the bigger, well designed studies [22,23,25–27] confirmed the findings derived from those studies. It is a challenge for future studies to overcome the expe-rienced limitations but also to focus more on mechanistic aspects of reproductive toxicity.
Semen analysisPresented studies usually have used classical human se-men parameters (concentration, motility and morphol-ogy), other markers have been used to get a more compre-hensive evaluation of spermatogenesis and the function of accessory sex organs (hormone levels, aneuploidy). A significant factor impeding the interpretation of stud-ies concerning semen quality is great variation in the same semen variables — in particular, ejaculate volume, sperm density and motility. The fluctuations across time within a man are nearly as great as the variation between men and can only partly be explained by the duration of the period of abstinence [8]. The concentration and probably also the sperm motility seem to be subject to seasonal variation, the best quality in the northern hemisphere be-ing registered during the winter and spring [67]. Seasonal variation accounts only for a part of total variation which, thus, remains largely unknown [8]. Experiments with rhe-sus monkeys suggest that the seasonal changes in semen quality may be driven by an inherent circannual biological clock reset annually by seasonal changes in the length of daylight [67]. Although there are some guidelines under WHO to intro-duce standardization and quality control in sperm labora-tory work [68], the assessment of semen quality — even within the same laboratory — may be subject to variation between technicians and related to time [69].
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(1995) [72] showed that p,p’-DDE had an antiandrogenic activity. Some pesticides are now suspected of being endocrine dis-rupting chemicals (EDCs). These chemicals might cause an adverse effect by interfering in some way with the body’s hormones or chemical messengers. Many of these endocrine disrupters have been linked to adverse effects on either embryonic development or reproductive func-tion in humans and wildlife [73–75].
Challenges for future studiesIt is necessary to conduct longitudinal studies. These stud-ies should take into account other factors which may in-terfere with male reproductive health and include other sperm characteristics. Future studies should have suffi-cient power and homogenous groups with an appropriate non-exposed control group. When the influence of confounding factors is possible, these should be taken into account during the stage of study design and data collection and finally in the statisti-cal analysis. Further evaluation of male reproductive tox-icity of commonly used substances or those that are likely to be in contact with human population is highly recom-mended. The longitudinal design option is a rational answer to several of the main limitations in the cross sectional ap-proach. Imprecision of measurement and variation be-tween observers can be reduced by implementing good laboratory practice and by computerised methods for ob-jective assessment of sperm motility. Also exposure assessment based on biomarkers of expo-sure should be used. As little is known about the basic mechanisms by which environmental exposures exert their effect, current studies should focus more on the explana-tion of the biological mechanism.
CONCLUSIONS
The results from the presented studies suggest that there are strong and rather consistent indications that some pesticides besides DBCP (as DDT/DDE, ethylenedibro-mide, organophosphates) affect sperm count. PCBs are
among controls. So, the possibility that the men available for the study may not truly reflect the source population is also the matter of concern. The cross-sectional approach is most often associated with considerable differential dropout and uncertainty about the comparability of exposed and non-exposed groups. It may be possible to overcome some of the major limi-tations of studies by choosing a longitudinal design with sampling before and during exposure and with a follow-up of intraindividual changes. Epidemiological models seem to have played increasing role in the risk assessment of reproductive health effects due to exposure to environmental factors. To be more informative, epidemiological studies should focus on ex-posure to single factors which were known from animal studies that they might bring health consequences. The factors which may influence the sperm count and explain part of the variability comprise the characteristics of the men included in the study, the methodologies used to analyse the semen or external factors influencing sperm production.
MechanismsExposure to environmental toxicants that disrupt sperm production or the function of reproductive hormones or sperm may increase the risk of male infertility. On the oth-er hand, chronic exposures to reproductive toxins are not well documented and mechanisms of toxicity are either poorly understood or unknown. Some evidences from ani-mal studies suggest that some pesticides and PCBs belong to the substances known as endocrine disrupters. PCBs and DDT are well known chemicals with estrogen-like characteristics and are referred to as estrogen disrupt-ers. Animal studies suggest that these chemicals readily penetrate the blood-testis barrier and can directly affect spermatogenesis. It was also documented that PCB me-tabolites bind to estrogen receptors. Jansen has hypoth-esized that adverse reproductive effects of PCBs may re-sult from PCB congeners increasing gonadotropin-releas-ing hormone or affecting the production and release of luteinizing hormone from the pituitary [71]. Kelce et al.
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