environmental endocrine disruption in san francisco bay fish effects assessment kevin kelley 1-3,...
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Environmental Endocrine Disruption Environmental Endocrine Disruption In San Francisco Bay Fish In San Francisco Bay Fish
Effects AssessmentEffects Assessment
Kevin KelleyKevin Kelley1-31-3, Jesus Reyes, Jesus Reyes1-31-3, Rusty , Rusty FaireyFairey44, Zed Mason, Zed Mason2,32,3, Cathy , Cathy PropperPropper55, Julianne Kalman, Julianne Kalman1,2,1,2,33
11EEL --Environmental Endocrinology Laboratory , Marine Biology EEL --Environmental Endocrinology Laboratory , Marine Biology ProgramProgram
22IIRMES --Institute for Integrated Research on Materials, Environment & IIRMES --Institute for Integrated Research on Materials, Environment & SocietySociety
33CEPA --Center for Education in Proteomics AnalysisCEPA --Center for Education in Proteomics Analysis
California State University, Long BeachCalifornia State University, Long Beach
44Marine Pollution Laboratory, Moss Landing Marine LaboratoriesMarine Pollution Laboratory, Moss Landing Marine Laboratories
55Northern Arizona UniversityNorthern Arizona University
66Cabrillo Marine Aquarium, San Pedro, CACabrillo Marine Aquarium, San Pedro, CA
ENDOCRINE SYSTEMSENDOCRINE SYSTEMS
regulateregulate
essential physiological functionsessential physiological functions
Reproduction Reproduction - - Somatic GrowthSomatic Growth - - MetabolismMetabolism Defense/ImmuneDefense/Immune - - ThyroidThyroid
- - Developmental Developmental Stress Stress ResponsesResponses - - NeuroendocrineNeuroendocrine - - othersothers
……Homeostasis, Adaptation, Homeostasis, Adaptation, Survival…Survival…
Some points about endocrine Some points about endocrine systemssystems::
. . . highly sensitive & responsive. . . highly sensitive & responsive
. . . respond to presence of environmental . . . respond to presence of environmental factors (stressors) to a degree factors (stressors) to a degree commensurate with the need to maintain commensurate with the need to maintain homeostasishomeostasis
. . . endocrine disturbances observed are . . . endocrine disturbances observed are typically indicative of the type of typically indicative of the type of environmental factor(s) actingenvironmental factor(s) acting
Monitoring programs can take advantage of endocrine disruptionendocrine disruption as a sensitive sensitive
screening toolscreening tool to assess effects assess effects (impacts)(impacts)
of water/environmental quality & specific contaminant effects
Endocrine-disrupting Endocrine-disrupting chemicals (EDCs)chemicals (EDCs) are present in are present in
marine and marine and estuarine estuarine
environments, environments, particularly along highly particularly along highly
populated coastal populated coastal regionsregions: :
SF Bay EstuarySF Bay Estuary http://toxics.usgs.gov/photo_gallery/sanfran.html
1-1- determine incidence and magnitude of determine incidence and magnitude of endocrine disruption in wild fishesendocrine disruption in wild fishes
thyroid, stress responses, growth & repair, reproduction
2- 2- determine whether spatial differences can be established between different SF
Bay locations
3- 3- determine liver contaminant determine liver contaminant concentrations in individualsconcentrations in individuals
Correlate specific contaminant concentrations with types/magnitude of endocrine disruption
STUDY STUDY OBJECTIVESOBJECTIVES
Shiner Surfperch
Cymatogaster aggregata
Pacific Staghorn Sculpin Leptocottus armatus
pelagicpelagic
benthicbenthic
San Pablo BaySan Pablo Bay
Berkeley Berkeley WaterfrontWaterfront
Oakland Inner Oakland Inner HarborHarbor
Redwood CityRedwood City
far-field far-field referencereference:: Tomales BayTomales Bay
2006 Field 2006 Field SitesSites[pilot year][pilot year]
Thyroid Hormones Thyroid Hormones
• broad physiological actionsbroad physiological actions• essential for essential for brain/neural brain/neural
developmentdevelopment• permissive to permissive to somatic growthsomatic growth• important regulators of important regulators of metabolismmetabolism
3,5,3’,5’-tetraiodothyronine (thyroxine)3,5,3’,5’-tetraiodothyronine (thyroxine) 3,5,3’-triiodothyronine 3,5,3’-triiodothyronine
T4T4 T3T3
0
20
40
60
80
100
San PabloBay
Berkeley Waterfront
RedwoodCity
Oakland Inner Harbor
Tomales Bay
(11) (19) (19) (9) (14)
Pla
sma T
hyro
xin
e
Pla
sma T
hyro
xin
e
(T4
) (T
4)
Conce
ntr
ati
on,
Conce
ntr
ati
on,
ng/m
lng/m
l
ShinerShiner
SurfpeSurfperchrch
Thryoxine (T4) Levels in Shiner Thryoxine (T4) Levels in Shiner SurfperchSurfperch
0
20
40
60
80
100
San PabloBay
Berkeley Waterfront
RedwoodCity
Oakland Inner Harbor
Tomales Bay
(8) (13) (17) (12) (5)
Pla
sma T
hyro
xin
e
Pla
sma T
hyro
xin
e
(T4
) (T
4)
Conce
ntr
ati
on,
Conce
ntr
ati
on,
ng/m
lng/m
l
Pacific Pacific StaghoStaghorn rn SculpiSculpinn
Thryoxine (T4) Levels in Pacific Thryoxine (T4) Levels in Pacific Staghorn SculpinStaghorn Sculpin
0
20
40
60
80
100
San PabloBay
Berkeley Waterfront
RedwoodCity
Oakland Inner Harbor
Tomales Bay
(8) (11) (13) (19) (17) (19) (12) (9) (5) (14)
Pla
sma T
hyro
xin
e
Pla
sma T
hyro
xin
e
(T4
) (T
4)
Conce
ntr
ati
on,
Conce
ntr
ati
on,
ng/m
lng/m
l
ShinerShiner
SurfpeSurfperchrch
Pacific Pacific StaghoStaghorn rn SculpiSculpinn
Thryoxine (T4) Levels in SF Bay Thryoxine (T4) Levels in SF Bay FishFish
Environmental Contaminants are Environmental Contaminants are Implicated in Thyroid Endocrine Implicated in Thyroid Endocrine
Disruption:Disruption:
……e.g., Phenols, Hg, Cd impair thyroxogenesis in thyroid e.g., Phenols, Hg, Cd impair thyroxogenesis in thyroid follicle cells in fish follicle cells in fish (Bhattacharya et al., ‘89)(Bhattacharya et al., ‘89)
……e.g., endosulfan, Aroclor 1254 and selected PCBs e.g., endosulfan, Aroclor 1254 and selected PCBs decrease T4 levels in fish, via effects on decrease T4 levels in fish, via effects on iodotyrosine iodotyrosine diodinasesdiodinases (Coimbra et al., ‘05; LeRoy et al., ‘06)(Coimbra et al., ‘05; LeRoy et al., ‘06)
……e.g., ioxynil, certain PCBs and PBDEs bind e.g., ioxynil, certain PCBs and PBDEs bind transthyretintransthyretin and TRs with high affinities, altering T4 and T3 levels/ and TRs with high affinities, altering T4 and T3 levels/ actions in fish actions in fish (Tomy et al., ‘04; Lema et al., ‘06; Morgado et al., (Tomy et al., ‘04; Lema et al., ‘06; Morgado et al., ‘07)‘07)
0
400
800
1200
1600
Redwood City
Oakland Inner
Harbor
Berkeley Waterfro
nt
San Pablo Bay
21 13 21 10
Shiner SurfperchPla
sma C
ort
isol
Conce
ntr
ati
on (
ng/m
l)
aa aa
bb
bb
Stress ResponseStress Response
0
400
800
1200
Redwood City
Oakland Inner
Harbor
Berkeley Waterfro
nt
San Pablo Bay
17 16 13 19
Pacific Staghorn SculpinPacific Staghorn Sculpin
Pla
sma C
ort
isol
Conce
ntr
ati
on (
ng/m
l) aa aa
bb
cc
Stress ResponseStress Response
Other wild fish species living in Other wild fish species living in affected marine environments exhibit affected marine environments exhibit
impairment of their impairment of their neuroendocrine stress response neuroendocrine stress response
systemsystem
...experimental studies have ...experimental studies have shown that contaminants, shown that contaminants,
--such as PCBs-- --such as PCBs-- impair stress responses in fishimpair stress responses in fish
((Quabius et al., 2005; Vijayan et al., 2006Quabius et al., 2005; Vijayan et al., 2006))
Thyroxine/Thyroxine/thyroidthyroid
IGF-I/IGF-I/growthgrowth
San PabloBay
Berkeley Waterfront
RedwoodCity
Oakland Inner Harbor
Tomales Bay
Shiner PerchShiner PerchPacific Staghorn Pacific Staghorn SculpinSculpin
Shiner PerchShiner PerchPacific Staghorn Pacific Staghorn SculpinSculpin
?? ???? ??
Endocrine Disruption—SF Bay Endocrine Disruption—SF Bay FishFish
S U M M A R Y –S U M M A R Y –Year 1Year 1
Cortisol/Cortisol/stress responsestress response Shiner PerchShiner PerchPacific Staghorn Pacific Staghorn SculpinSculpin
Testosterone/Testosterone/ReprodReprod
1717αα-Ethinylestradiol/-Ethinylestradiol/Pharm.Pharm.
Endocrine Disruption—SF Bay Endocrine Disruption—SF Bay FishFish
San PabloBay
Berkeley Waterfront
RedwoodCity
Oakland Inner Harbor
Tomales Bay
Pacific Staghorn Pacific Staghorn SculpinSculpin
Pacific Staghorn Pacific Staghorn SculpinSculpin
1717ββ-Estradiol/-Estradiol/Reprod.Reprod.
Pacific Staghorn Pacific Staghorn SculpinSculpin
S U M M A R Y –S U M M A R Y –Year 1Year 1
immatureimmature
Endocrine Disruption—SF Bay Endocrine Disruption—SF Bay FishFish
San PabloBay
Berkeley Waterfront
RedwoodCity
Oakland Inner Harbor
Tomales Bay
Shiner PerchShiner PerchPacific Staghorn Pacific Staghorn SculpinSculpin
Shiner PerchShiner PerchPacific Staghorn Pacific Staghorn SculpinSculpin
Shiner PerchShiner PerchPacific Staghorn Pacific Staghorn SculpinSculpin
?? ?? ?? ?? ??
?? ?? ?? ?? ??
S U M M A R Y –S U M M A R Y –Year 1Year 1
1717ββ-Estradiol/-Estradiol/Reprod.Reprod.
1717αα-Ethinylestradiol/-Ethinylestradiol/Pharm.Pharm.
Testosterone/Testosterone/ReprodReprod
Contaminant Analyses:Contaminant Analyses:• Feasible to measure individuals liver Feasible to measure individuals liver
contaminant levels (PCBs, PAHs, contaminant levels (PCBs, PAHs, pesticides)pesticides)
• Several contaminants measured at high Several contaminants measured at high concentrations in shiner perch and Pacific concentrations in shiner perch and Pacific staghorn sculpinstaghorn sculpin
• Relatively higher levels of contaminants in Relatively higher levels of contaminants in livers of Pacific staghorn sculpinlivers of Pacific staghorn sculpin
• Feasible to correlate individual liver Feasible to correlate individual liver contaminant concentrations with contaminant concentrations with endocrine and physiological indices endocrine and physiological indices
San Pablo Bay San Pablo Bay (Loch Lohmand Marina) (Loch Lohmand Marina)
Richmond/Berkeley WaterfrontRichmond/Berkeley Waterfront
Oakland Inner HarborOakland Inner Harbor
Redwood CityRedwood City
Tomales BayTomales Bay
Bodega BayBodega Bay
Study SitesStudy Sites [August 2007][August 2007]
RichmondRichmond (Lauritzen Channel, (Lauritzen Channel,
DDTsDDTs))
San Leandro BaySan Leandro Bay (PCBs)(PCBs)San Francisco San Francisco WaterfrontWaterfront Hunter’s PointHunter’s Point (POTW)(POTW)
Two Harbors –Santa Catalina IslandTwo Harbors –Santa Catalina Island (Pacific (Pacific
side)side) L.A. Harbor –Inner Cabrillo BeachL.A. Harbor –Inner Cabrillo Beach (collab. w/CMA)(collab. w/CMA)
THYROID THYROID Thyroxine & TriidothyronineThyroxine & Triidothyronine
REPRODUCTION REPRODUCTION Testosterone Testosterone & & 11-ketotestosterone11-ketotestosterone
REPRODUCTION REPRODUCTION 1717ββ-Estradiol, -Estradiol, 1717αα-Ethinylestradiol, Vitellogenin-Ethinylestradiol, Vitellogenin
STRESS STRESS Cortisol & CortisoneCortisol & Cortisone
GROWTH GROWTH IGF-I & IGFBPsIGF-I & IGFBPs
Endocrine Endocrine Parameters in Parameters in
2007-82007-8
• Altered thyroxine levels.Altered thyroxine levels. -- -- T4 measurementT4 measurement
• Altered T3 levels, T4:T3 ratios?Altered T3 levels, T4:T3 ratios? -- -- T3 measurement, calculate T3 measurement, calculate T4:T3T4:T3
• Altered thyroid gland morphology?Altered thyroid gland morphology? -- -- Thyroid histologyThyroid histology
• Impaired thyroid responsiveness?Impaired thyroid responsiveness? -- -- TSH-challenge TSH-challenge • Altered T4 metabolism or TH receptors?Altered T4 metabolism or TH receptors? -- -- peripheral peripheral
iodotyrosine deiodinasesiodotyrosine deiodinases (ID1-3),(ID1-3), TRTRαα, TR, TRββ
Emphasis:Emphasis: Thyroid Endocrine (HPT) Thyroid Endocrine (HPT) AxisAxis
• Impaired growth?Impaired growth? -- -- Growth & IGF system indicesGrowth & IGF system indices [[IGF-I, IGFBPs, cartilage growth activity]IGF-I, IGFBPs, cartilage growth activity]
• Relationships with specific bioaccumulated chemicals?Relationships with specific bioaccumulated chemicals? -- -- Hepatic contaminants measurement & correlationHepatic contaminants measurement & correlation
Underlying MechanismsUnderlying Mechanisms::
Environmental ContaminantsEnvironmental Contaminants::
Physiological ImpactsPhysiological Impacts::
Emphasis:Emphasis: Stress Endocrine (HPI) Stress Endocrine (HPI) AxisAxis
• Altered cortisol levels.Altered cortisol levels. -- -- Cortisol measurementCortisol measurement• Altered interrenal gland morphology?Altered interrenal gland morphology? -- -- Interrenal histologyInterrenal histology • Altered metabolism of cortisol?Altered metabolism of cortisol? -- -- cortisone measurementcortisone measurement• Impaired interrenal responsiveness?Impaired interrenal responsiveness? -- -- ACTH-challengeACTH-challenge• Impaired production of cortisol?Impaired production of cortisol? -- -- steroidogenic enzyme steroidogenic enzyme
expressionexpression (StAR, 11(StAR, 11ββ-hydroxylase, 11-hydroxylase, 11ββ-HSD-2)-HSD-2)
• Relationships with specific bioaccumulated chemicals?Relationships with specific bioaccumulated chemicals? -- -- Hepatic contaminants measurement & correlationHepatic contaminants measurement & correlation
• Impaired defense?Impaired defense? -- -- Parasitic infestation assessmentParasitic infestation assessment
• Impaired growth?Impaired growth? -- -- Growth & IGF system indicesGrowth & IGF system indices [[IGF-I, IGFBPs, cartilage growth activityIGF-I, IGFBPs, cartilage growth activity]]
Underlying MechanismsUnderlying Mechanisms::
Environmental Environmental ContaminantsContaminants::
Physiological ImpactsPhysiological Impacts::
I.I. Endocrine responses Endocrine responses and/orand/or endocrine disruption endocrine disruption serve as serve as sensitive bio-markerssensitive bio-markers of environmental of environmental perturbations perturbations
II.II. Endocrine systems areEndocrine systems are::
--highly --highly sensitivesensitive to environmental to environmental stressorsstressors
----respond proportionallyrespond proportionally to the need to to the need to maintain maintain homeostasishomeostasis
--show alterations --show alterations reflective of the kind of reflective of the kind of stressor(s) stressor(s) presentpresent (different EDCs affect (different EDCs affect different endocrine different endocrine axes via distinct axes via distinct underlying mechanisms)underlying mechanisms)
SUMMARY POINTSSUMMARY POINTS
III. III. Endocrine-disrupted conditions are observed in Endocrine-disrupted conditions are observed in SF Bay fishSF Bay fish (urban, industrial, boat marinas)(urban, industrial, boat marinas)
IV. Endocrine disruption is IV. Endocrine disruption is evident in different fish evident in different fish speciesspecies
V. Endocrine disruption is V. Endocrine disruption is occurring in different occurring in different endocrine systemsendocrine systems (stress, thyroid, reproduction, growth (stress, thyroid, reproduction, growth
& repair, & repair, defense, metabolism)defense, metabolism)
VI. There may be VI. There may be interactions among endocrine interactions among endocrine systemssystems (means wider impacts on physiological (means wider impacts on physiological performance)performance)
SUMMARY SUMMARY POINTSPOINTScontinuedcontinued
A.A. Identification of specific chemicals associated Identification of specific chemicals associated with endocrine disruptionwith endocrine disruption
B. Understand mechanisms and test candidate B. Understand mechanisms and test candidate EDCs, to establish cause and effectEDCs, to establish cause and effect
C. Build models to estimate ecologically relevant C. Build models to estimate ecologically relevant performance alterations from measures of performance alterations from measures of endocrine disruption endocrine disruption (growth, reproduction, (growth, reproduction, disease/parasitism)disease/parasitism)
D. Determine contaminant thresholds of effectsD. Determine contaminant thresholds of effects
E. Use new technologies (proteomics) to build E. Use new technologies (proteomics) to build integrated phenotypic biomarker fingerprintsintegrated phenotypic biomarker fingerprints (multifactorial screen) (multifactorial screen)
DIRECTIONDIRECTION
Long Beach Env’l. Long Beach Env’l. Endo. Lab.Endo. Lab.
Jesus Reyes, Kathy Sak, Andrew Hamilton, Becki Hagstrom, Maelanie Galima, Dawn Petschauer, Navdeep Brar, Tiffany Price, Tuan Truong, Dana Cianfrani, Shari Smolko, Tami Gonzalez, Claire Wingard, Kenna Koons, Julianne Kalman, Scott Adams, Wendy Hall
?
http://www.csulb.edu/depts/endo
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City of Los Angeles Bureau of
City of Los Angeles Bureau of
Sanitation Sanitation Env’l Monitoring Division
Env’l Monitoring DivisionLos Angeles County
Los Angeles County
Sanitation Districts
Sanitation Districts
Southern California Coastal
Southern California Coastal
Water Research Project
Water Research Project
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Long Beach –IIRMES & CEPA
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Marine Pollution Laboratory
Marine Pollution Laboratory
Northern Arizona Univ. Northern Arizona Univ.
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