Physiology of Women Reproduction System

Introduction of the internal reproductive organs

• The vagina is a muscular canal, which leads from the uterus to the valva

• the uterus is a hollow, smooth-muscled organ. It is lined by a glandular epithelium, the endometrium. It is related to menstruation.

• The fallopian or uterine tubes each fallopian tube extends outwards from the uterine cornu to end near the ovary. The tubes, or oviducts, convey the ovum from the ovary towards the uterus, providing oxygenation and nutrition for sperm, ovum and zygote,should fertilization occur.

• The ovaries are two almond-shaped solid organs, measuring about 3.5cm in length, 2cm in depth and 1cm in thickenss.

Whole life of women’s

• Neonatal period within four weeks after birth• childhood from after four weeks to less than 10

years old• puberty • sexual maturity (reproductive years, childbearing

years) from 18• perimenopausal period round 50 years old• Senility more than 65

Menstruation and its clinical features

1. menstruation: defined as uterine bleeding in a

regular, recurring and predictable occurs once a

month .menstruation is established at puberty

(around age 13) and continues until the time of

menopause at around age 50 .Thus a woman has

approximately 30 ～ 40 years of reproductive

function.

2. menarche: menstruation first occurs. This is the most d

efinite sign that puberty has commenced. Over the last 100 ye

ars. the average age of the menarche has steadily declined fro

m age of 14 ～ 16 years to 11 ～ 15 years. This changes is prob

ably related to better nutrition and increased body weight in

adolescents . Conversely the menarche is delayed in girls suff

ering from malnutrition. The age of the menarche is not relat

ed to climate. The onset of menstruation does not directly equ

ate with the onset of fertility as the early menstrual cycles in a

dolescents are often anovular.

3. menstrual cycle: The length of a menstrual cycle

is counted in days from the first day of bleeding to t

he first day of next cycle. The length of the normal c

ycle varies from woman to woman and from time to

time in the same woman. The 1st day of menstruatio

n is considered day 1 of the menstrual cycle .The ave

rage duration of a menstrual cycle is 28 ～ 30 days.

but variations of 21 ～ 35 days are accepted as withi

n normal limits. Cycles shorter or longer than this a

re more likely to be anovulatory.

4. menstrual period: The duration of the menstr

ual flow is very variable ,the average is 3 ～ 5 day

s, durations of 1 ～ 8 days can be normal. The am

ount of menstrual flow peaks on the first or seco

nd day of menstruation. The amount of blood los

s during menstruation is approximately 30 ～ 50

ml. ranged from 20 ～ 80ml, more than 80ml is c

onsidered menorrhagia.

5. menstrual flow consists of nonclotting blood ,

mucus ， cellular debris and endometrium fragme

nts.

The menstrual flow is usually scanty and viscid

at first, later becoming bright red, and finally brow

n towards the end of the period. Small clots and fra

gment of endometrium may be seen, but large clots

are only passed when the bleeding is excessive.

• Symptoms of menstrual period: There may be ab

dominal discomfort, headache, soreness of breast

s, feeling of tired etc .Usually these symptoms are

not severe.

• The most obvious manifestation of the normal menstru

al cycle is the presence of regular menstrual periods. T

hese occur as the endometrium is shed following failure

of implantation or fertilization of the oocyte.

• Why women have recurring ， regular menstrual cycle?

• The menstrual cycle depends on the cyclic interaction bet

ween hypothalamic gonadotropin–releasing Hormone(Gn

RH),the pituitary gonadotropins follicle–stimulating horm

one (FSH) and luteinizing hormone (LH),and the ovarian s

ex steroid hormones estradiol and progesterone .Through

positive and negative feedback loops, these hormones stimu

late ovulation, and bring about menstruation .If any one (o

r more ) of the above hormones becomes elevated or suppr

essed, the menstruation cycle will becomes disorder ,or ovu

lation and menstruation cease.

Hypothalamic GnRH secretion• The hypothalamus ,via the pulsatile secretion of GnRH, stimulates pituit

ary LH and FSH secretion.

GnRH is a decapeptide hormone , it is secreted in a pulsatile manne

r from the arcuate nucleus of the hypothalamus. The mechanism for sti

mulation of GnRH secretions is unknown. however, GnRH secretion is i

nfluenced by estradiol and catecholamine etc neurotransmitters. GnRH

reaches the anterior pituitary gland through the hypothalamic –pituitary

portal plexus. Pituitary gonadotropin secretion is stimulated and regulat

ed by the pulsatile secretion of GnRH.

Pituitary gonadotropin secretion

• The pituitary gonadotropins FSH and LH are protein hormones

secreted by the anterior pituitary gland. FSH and LH are also secre

ted in pulsatile fashion in concert with the pulsatile release of GnR

H, the quantity of secretion and the rates of FSH/LH are determin

ed largely by the levels of ovarian steroid hormones and other ova

rian factors .When a woman is in a state of relative estrogen defici

ency, the principal gonadotropin secreted is FSH. FSH stimulates t

he follicular development, maturation and the production of estro

gen. LH induces ovulation of mature follicle, corpus lutein formati

on and the production of progesterone and estrogen.

H-P-O axis

hypothalamic --------------GnRH

Pituitary -----------gonadotropin (FSH,LH)

ovary---------- sex steroid hormone

Uterus and other organs

Ovarian functions and its cyclic changes

Ovarian functions

1. Reproductive function: provides oocyte monthly.

2. Endocrine function: produces steroid hormones during the follicle

grows.

• Within the ovary, the menstrual cycle can be divided into three phas

es:

the follicular phase

ovulation

the luteal phase

•

menstrual cycle

Menstruation follicular phase ovulation luteal phase

Sheding ofendometruim

development of follicles

escape of oocyte

formation of corpus luteum

Premordial preantral antralPreovulatory

Or mature

Ovarian Cyclic Changes 1. Development and maturation of follicle (the follicular phase

in the menstrual cycle )

The ovary contains thousands of the primordial follicles. Follicles fir

st form in the female fetus during the fourth month of pregnancy , these

primordial follicles are the smallest ， about 50μm in diameter, and ab

out 7 million are formed initially. At birth, their number has declined to

about 2 million.

Each primordial follicle contains an oocyte, surrounded by a single

layer of pregranulosa cells.(see Fig.)

The development of the oocyte is the key event in the follicular phase of the menstr

ual cycle.

Development beyond the preantral stage is stimulated by t

he pituitary hormones,LH and FSH,which can be considered

as key regulators of oocyte development.

• at the start of the menstrual cycle, FSH levels begin to rise

as the pituitary is released from the negative feedback effects

of progesterone, oestrogen. Rising FSH levels rescue a cohort

of follicles from atresia, and initiate steroidogenesis.

• After puberty, a constant small proportion of follicles start growin

g each day but only about 400 will ever release a mature oocyte, a

far greater number never mature and finally undergo atresia.

• As a primordial follicle is stimulated by FSH ， the oocyte enlarg

es, surrounded by a membrane, the zona pellucida; pregranulosa c

ells become granulosa cells ， which begin proliferation and secret

ing estradiol; the stroma surrounding the granulosa cells begin to

organize the thecal layer, which secrete androgens. These follicles

are named preantral follicle, about 200 μm in diameter.

Under the synergistic influence of estrogen and FSH t

here is a concomitant increase in the production of folli

cular fluid, which accumulates in the intercellular spac

es of the granulosa to form a cavity, this stages of follic

le is called antral follicle (or developing follicle ), about

500μm in diameter, granulosea proliferate to become

multilayer, the theca is broadly divided into two layer;

theca folliculi internal and theca folliculi external.

During a full reproductive cycle, one oocyte is br

ought to maturity before ovulation. In the process of

bringing one oocyte to maturation, a number of oocy

tes are stimulated to partial maturation but subsequen

tly undergo atresia before reaching ovulation. one of

ripe follicles ruptures at about day 14 of each menstr

ual cycle to discharge its oocyte. the follicles which r

upture are converted into a corpus luteum, which eve

ntually retrogresses and becomes a corpus albicans. •

• Steroidgenesis• The basis of hormonal activity in preantral to preovulatory fo

llicles is described as the “two cell, two gonadotrophin” hypothe

sis.steroidogenesis is compartmentalized in the two cell types w

hthin the follicle: the theca and granulosa cells. The two cell, tw

o gonadotrophin hypothesis states that these cells are responsiv

e to the gonadotrophins, LH and FSH respectively.

• Within the theca cells, LH stimulates the production of andro

gens from cholesterol. Within granulosa cells, FSH stimulates t

he conversion of thecallyderived androgens to oestrogens(arom

atization). In addition to its effects on aromatization, FSH is als

o responsible for proliferation of granulosa cells.

•

• Ovarian steroidogenesis.the ovary has the capacity to synthesize oestradiol from cholesterol. The major products of the ovary are oestradiol and progesterone although small amounts of testosterone and androstenedione are also produced. See Fig.

• Dominant follicle

the developing follicle grows and produces steroid hormones under the influence of the gonadotrophins LH and FSH. These gonadotrophins rescue a cohort of prantral follicles from atresia. However, normally only one of these follicles is destined to grow to a preovulatory follicle and be released at ovulation-the dominant follicle.

the dominant follicle is the largest and most developed follicle in the ovary at the mid-follicular phase. Such a follicle has the most efficent aromatase activity and the highest concentration of FSH-induced LH receptors.

for various causes the largest follicle requires the lowest levels of FSH(and LH) for continued development.

• In a lot of developing follicle ,only one leading follicle

(dominant follicle) can reach maturation (≥20mm in di

ameter ) and ovulation during a menstrual cycle, It is c

alled mature follicle (or preovulatory follicle ).The cavit

y of mature follicle enlarge, follicular fluid increase, oo

cyte is pushed to one side of follicle, follicle moved towa

rds the surface of ovary .

• The phase of follicle development , from primordial to

mature ,is called follicular phase .

2. Ovulation

The process during which a mature follicle ruptures to rel

ease a mature oocyte with some granulosa cells and follicular

fluid .The mechanism for ovulation is not very clear, LH surg

e is necessary for ovulation, it precipitates the final maturatio

n of follicle, changes in the follicular wall and follicular fluid

volume. LH surge also increase production of intrafollicular

prostaglandins which play an essential role in release of the o

ocyte, the administration of prostaglandin synthetase inhibito

rs will cause the oocyte to be retained within the follicle durin

g the luteal phase of the cycle.

• In addition. some enzymes play a role for ovulation. In

humans spontaneous ovulation usually occurs 24 ～36h after the LH surge.

• Ovulation usually occurs 14 days before the next

expected menstruation, i. e. around at day 14 in a 28

days cycle .In longer cycles ovulation occurs later, i.e.

around day 19 in a 33days cycle. In many women,

ovulation may be associated abdominal discomfort or

pain.

3. Formation and degeneration of corpus luteum ( lute

al phase in the menstrual cycle)

After ovulation follicle collapsed, original granulosa cells enlarge, accu

mulating yellow lipid, called granulosa corpus lutein cells , meanwhile thec

a cells become theca corpus lutein cells, right now, corpus luteum formed .

the luteal phase is characterized by the production of progesterone fro

m the corpus luteum within the ovary.

About 7 ～ 8 days after ovulation ， the corpus lutein development reac

h maturation,2 ～ 3cm in diameter ,at the time the corpus leteum secretes

maximal estrogen and progesterone . The production of progesfterone fro

m the corpus luteum is dependent on continued pituitary LH secretion.

•

If fertilization and implantation do not occur, at 9 ～ 10 day

s after ovulation the corpus luteum begins degeneration ,it dec

reases in volume and loses its yellow color ,hormones producti

on diminishes rapidly ,cells denatured ,menstruation ensues le

ading to the beginning of a new cycle .

The corpus luteum has a fixed life period, about 13 ～ 14 d

ays unless pregnancy occurs .If the oocyte becomes fertilized a

nd implants within the endometrium, the early pregnancy begi

ns secreting human chorionic gonadotropin (HCG),which sup

port the corpus luteum for another 6 ～ 7 weeks. If there has b

een no pregnancy, after 8 ～ 10 weeks the corpus luteum beco

mes a white fibrous streak within the ovary called the corpus a

lbicans .The phase from formation to degeneration of corpus l

uteum called luteal phase.

If there has been no pregnancy, after 8 ～ 10

weeks the corpus luteum becomes a white fibro

us streak within the ovary called the corpus alb

icans .The phase from formation to degeneratio

n of corpus luteum called luteal phase. However,

serum levels of progesterone are such that LH and FSH

production is relatively suppressed. So a menstrua

l cycle is divided into follicular phase ， Ovulat

ion phase and luteal phase .

Sex steroid hormones secretion in ovaries

The ovaries secrete estrogen (E) ， progesterone (P) and androgens (A) .

During the process of follicular maturation, binding of FS

H to receptors in the granulosa cells causes granulosa cell prol

iferation and continuously increased production of estradiol

(E2). The follicle with the greatest number of granulosa cells ,

FSH receptors and the highest E2 production becomes the dom

inant follicle from which ovulation will occur .The theca cells s

ecrete A, which serve as the precursors for E production by th

e granulosa cells.

The basic substance provides for sex hormone sy

nthesis is cholesterol from food intake. E is secreted

through a two-cell mechanism . Androgens are first

secreted by the theca cells, these A enter the granulo

sa cells by diffusion , where they are aromatized to

E.

After ovulation, the mature follicle becomes to c

orpus luteum .the luteal phase of the cycle is charact

erized by a change in secretion of sex steroid hormo

nes from E predominance to P predominance.

As FSH rises early in the cycle and stimulates m

itosis of granulosa cells and production of E, ad

ditional LH receptors are created in the granul

osa cells and theca cells .With the LH surge at t

he time of ovulation ,these LH receptors bind L

H and convert the enzymatic machinery of the

granulosa and theca cells to facilitate productio

n of P.

Androgens are metabolic precursors of

E and are found in small amounts in the

blood and urine of normal women. They

are secreted by the suprarenal cortex and

stromal cells of ovary.

Physiological actions of E and P

1. Uterus

• E: accelerates uterine development, myometrial thickn

ess ， uterine blood supply, smooth muscle contractilit

y and sensitivity to oxytocin.

• P: uterine blood supply increase, reduces smooth muscl

e contractility and sensitivity to oxytocin.

2. endometrium

• E: stimulates the endometrial stroma thickens an

d the glands proliferate ， this is a proliferative e

ndometrium.

• P: converts the proliferative endometrium into a

secretory endometrium. After ovulation the corp

us luteum secretes both oestrogen and progestero

ne, and these bring about progestational changes

in the endometrium.

3. cervical mucosa

• E: the endocervical glands secrete large quantitie

s of thin ， clear, watery mucus. On drying ， s

hows fern-like crystals.

• P: cervical mucus become thick , clouding, and te

nacious 。 On drying ， ellipsoid appeared. see

4. fallopian tube

• E: augment the amplitude of rhythmic contractio

n, accelerates fallopian tube development.

• P: reduces the amplitude of rhythmic contraction.

5. Vagina epithelium

• E: Stimulates vaginal epithelium proliferates and

mature, glycogen increase ， causes the vaginal P

H to be low (PH=4 ～ 5).

• P: accelerates vaginal epithelial cells shedding.

6. breasts

• E: mammary gland duct proliferates. high level o

f E inhibits milk secretion.

• P: accelerates the growth of alveolus and lobular.

high level of P inhibits milk secretion.

7. Body temperature regulation

E: no action

• P: make basal body temperature (BBT)rises 0.

3 ～ 0.5oC by affect Hypothalamic thermoregula

ting center.

8. H-P

E: there are both negative and positive feedback

to H-P.

P: there is negative feedback only.

10. bone:

E ： promote calcium deposits in bone.

Summary of ovarian eventsFollicular phase• LH stimulates theca cells to produce androgens• FSH stimulates granulosa cells to produce oestrogens• the most advanced follicle at mid-follicular phase

becomes the dominant follicle• rising oestrogen produced by the dominant follicle inhi

bit pituitary FSH production• declining FSH levels carse atresia of all but the demina

nt follicle

Ovulation• FSH induces LH receptors

• LH surge

• proteolytic enzymes within the follicle carse follicular wall breakdown and release of the oocyte

The luteal phase

• the corpus luteum is formed from granulosa and theca cells retained after ovulation

• progesterone produced by the corpus luteum is the dominant hormone of the luteal phase

• A delicate balance of FSH and LH is required for early follicular d

evelopment. The ideal situation for the initial stages of follicular d

evelopment is low LH levels and high FSH levels, as seen in the ear

ly menstrual cycle. If LH levels are too high, theca cells produce la

rge amounts of androgens carling follicular atresia.

• The interrelation of Hypothalamic-pituitary -ovarian Axis (H-P-O Axis)