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The Female Reproductive System

Primary Sex Organs:

A pair of ovaries
1. Gametogenic function - Oogenesis and cyclical release of ovum
2. Endocrine function - Production of oestrogens, progesterone, relaxin and inhibin

Secondary (Accessory) Sex Organs:

1. The Uterus:
1.1 Uterine Tubes:
Collect and transport ovum (or zygote) into the uterine cavity by means of fimbriae, ciliary
activity and peristalsis
1.2 Uterine Body:
a. the endometrium (mucosa) – accommodates and nourishes the zygote (conceptus)
b. the myometium (muscle coat) – expels the fetus at parturition

1.3 Cervical Canal:

the cervical mucus guards the uterine cavity; allows passage of spermatozoa; facilitates
the descent of fetus at parturition
2. Vagina:
a copulatory organ where seminal fluid is deposited; acts as birth canal

3. External Genitalia (vulva, clitoris):

Sexual stimulation

4. Breasts (mammary glands):

Lactation

The Menstrual Cycle

During the reproductive period, the reproductive system of the female shows regular cyclical
changes that may be regarded as periodic preparation for fertilization and pregnancy.

Menstruation:
It is the periodic vaginal bleeding that occurs with the shedding of the uterine mucosa.

Length of the Cycle – variable with the average of 28 days from the start of one menstrual period to the
start of the next.

1. The Ovarian Cycle (Changes in the ovaries during the menstrual cycle)
➢ From the time of birth, there are many primordial follicles under the ovarian capsule.
➢ At puberty only 300,000 left.
➢ Each contains an immature ovum.

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 ➢ At the start of each cycle, several of these follicles enlarge, and a cavity forms around the ovum.
The cavity is filled with follicular fluid.
➢ On the 6th day of menstrual cycle, one of the follicles grows rapidly and becomes the dominant
follicle (graafian follicle). The others regress (atretic follicles).

➢ Theca interna of the graafian follicle secrete estrogens into blood circulation.
➢ Granulosa cells secrete oestrogens into follicular fluid.
➢ At the 14th day of the cycle, the graafian follicle ruptures and ovum is extruded into the
abdominal cavity. It is called ovulation.
➢ The ovum is picked up by the fimbriated ends of the fallopian tube and transported to the uterus.
➢ If there is no fertilization, ovum is out through the vagina.
➢ Ruptured follicle is filled with blood (corpus haemorrhagicum).
➢ Minor bleeding from the follicle into the abdominal cavity may cause peritoneal irritation and
lower abdominal pain (Mittelschmerz).
➢ The granulose and theca cells of the follicle promptly begin to proliferate and the blood is
replaced with yellowish, lipid-rich luteal cells (corpus luteum).
➢ If fertilization of the ovum occurs, corpus luetum persists. If not, corpus luteum begins to
degenerate usually on the 24th day of the menstrual cycle and is replaced by scar tissue (corpus
albicans).

2. The Uterine Cycle

2.1 Endometrial Cycle

a. Repair or Proliferative Phase

(Under the influence of estrogens secreted from the ovarian follicle)
➢ 5th to 14th day (variable)
➢ Reepithelization and revascularization from the basal endometrial layers. Thickness of
endometrium: increases from about 1 mm to 3 to 4 mm
➢ Progressive lengthening of endometrial glands
➢ Hypertrophy of stromal cells
➢ Endometrial prostaglandin level is low
➢ Function: restoration of endometrium from preceding menstruation.

b. Preparatory or Secretory Phase

(Under the influence of estrogens and progesterone secreted from corpus luteum)
➢ 15th to 28th day (duration of 14 days is fixed)
➢ Maximal thickness of endometrium is 5 to 7 mm
➢ Endometrial glands continue lengthening and tortuous. They begin to secrete mucus and glycogen
➢ Stroma : superficial cells enlarge and become compact; middle layer is oedematous and spongy
➢ Endometrial prostaglandin level is high
➢ Function: preparation of uterus for implantation of fertilized ovum.

c. Menstrual Phase
(Due to withdrawal of hormonal support)

➢ If there is no fertilization, corpus luteum regresses.

➢ Oestrogens and progesterone falls.

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 ➢ Hormonal support for the endometrium is withdrawn.
➢ Endometrium becomes thinner; spiral arteries become coiled and tortuous.
➢ Foci of necrosis appear in the endometrium and these coalesce.
➢ In necrotic endometrial cells, lysosomal membranes break down. Enzymes release and they
promote prostaglandins formation.
➢ Prostaglandins cause spasm and necrosis of the walls of the spiral arteries, leading to sloughing
of the overlying necrotic uterine mucosa. This produces the menstrual flow.

Normal menstruation
➢ It is predominantly arterial.
➢ 75% arterial and 25% venous origin.
➢ contains tissue debris, prostaglandins and fibrinolysin
➢ duration is 3 to 5 days. (range 1 to 8 days)
➢ amount is 30 to 80 ml (> 80ml is abnormal)

Bleeding can occur without ovulation. This is known as “anovular menstruation.”

1.2. The Myometrial Cycle

Follicular Phase: Recording of myometial contractions show small irregular waves with increasing
frequency (greatest at ovulation)
Luteal Phase Much larger waves with longer duration.

2. The Cervical Cycle

Follicualr Phase
Cervical mucus: thin, alkaline and elastic (“spinnbarkeit”)
Cervical smear: an arborising fern-like pattern (ferning = crystals of NaCl, KCl).
Thinnest and most profuse at ovulation which may causes a white vaginal discharge
called “ovulation cascade”.
Luteal Phase
Cervical mucus: thick, tenacious and cellular
Cervical smear: fails to form fern pattern when allowed to dry

3. The Vaginal Cycle

Follicular Phase
Vaginal epithelium: Cornification
Vaginal Smear:
Large polyhedral cornified epithelial cells with pyknotic nuclei.
Luteal Phase
Vaginal epithelium: Proliferation and secretion of epithelium which becomes infiltrated with
leucocytes.
Vaginal Smear:
Intermediate sized cells with rolled edges; prominent infiltration with leucocytes

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4. Breast Changes

Follicular Phase
Proliferation of ducts
Luteal Phase
Further proliferation of ducts and formation of alveoli; congestion and oedema of “premenstrual
breast fullness” sometimes with pain and tenderness

Indicators of Ovulation

The best proof of ovulation is pregnancy. In its absence, ovulation may be recognized by:-
1. Biphasic basal body temperature chart, about 0.5ºC higher is the last 14 days of the cycle.
Progesterone secreted from corpus luteum has thermogenic effect.
2. “Mittelschmerz” – midcycle lower abdominal pain (not very specific).
Minor bleeding from the follicle into the abdominal cavity may cause peritoneal irritation and
lower abdominal pain.
3. Evidence of progestational changes in endometrium
Endometrial biopsy
✓ Endometrial glands continue lengthening and tortuous
✓ Stroma : superficial cells enlarge and become compact; middle layer is oedematous and
spongy
✓ Endometrial prostaglandin level is high.
Cervix
✓ Cervical mucus: thick, tenacious and cellular
✓ Cervical smear: fails to form fern pattern when allowed to dry

Vagina
✓ Vaginal epithelium: Proliferation and secretion of epithelium which becomes infiltrated
with leucocytes.
✓ Vaginal smear: Intermediate sized cells with rolled edges; prominent infiltration with
leucocytes

4. An increase in serum progesterone or urinary pregnanediol in the second half of the cycle or
midcycle rise in serum gonadotropins (LH, FSH)
5. Direct observation (at laparotomy or by laparoscopy) of a recently formed corpus luteum or
haemorrhagic spot (corpus haemorrhagicum) in the ovary: or isolation of the ovum in tubal
washings.

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Control of Ovarian Function
I. During the menstrual cycles (control of the menstrual cycle)
II. During pregnancy

I. Control of Ovarian Function during the Menstrual Cycle

Ovarian function is controlled by gonadotrophins and GnRH along the hypothalamo-
adenohypophyseal-ovarian axis with ovarian hormones exerting negative feedback at both the pituitary
and hypothalamic levels.
Hypothalamic control is in turn influenced by a number of neural and humoral inputs.

Hypothalamic Control
➢ Hypothalamic neurons secrete GnRH in episodic bursts at intervals of 30-60 min (circhoral
secretory rhythm).
➢ These episodic bursts of GnRH secretion are essential for normal secretion of FSH and LH.
Constantly high levels of GnRH cause down-regualation of GnRH receptors. LH secretion falls. But
episodic administration of GnRH (e.g. one pulse per hour) stimulates LH secretion.
➢ Emotional stress such as moving away from home or fear of pregnancy depresses hypothalamic
secretion of GnRH and cause cessation of menstruation (e.g. “boarding school or hostel
amenorrhora”).

Pituitary Control
FSH is responsible for the maturation of the ovarian follicles and oestrogen secretion from ovarian
follicles.
LH is responsible for:
1. final maturation of the ovarian follicles (synergistically with FSH)
2. oestrogen secretion from the ovarian follicles
3. ovulation (LH surge is essential)
4. initial formation of the corpus luteum (luteinizing action)
5. maintenance of the corpus luteum (luteotrophic action)
6. production of oestrogen and progesterone from the corputs luteum

II. Control of Ovarian Function during Pregnancy

➢ If there is fertilization, the corpus luteum continues to grow and secretes estrogen, progesterone
and relaxin.
➢ Pituitary secretion of LH and FSH are inhibited.
➢ Human chorionic gonadotrophin (hCG) secreted from placenta stimulates ovarian production of
estrogen and progesterone which are essential for maintenance of pregnancy.
➢ After the 6th week of pregnancy, the placenta produces sufficient estrogen and progesterone to
take over the function of the corpus luteum.
➢ Corpus luteal function begins to decline after 8th week of pregnancy but it persists throughout
pregnancy.

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 Luteolysis next cycle

Decreased estrogen and progesterone secretion from the corpus luteum

Fall in plasma estrogen and progesterone levels

Increased secretion GnRH Withdrawal of hormonal support

Menstruation
Increased secretion of FSH and LH

Development of a new crop of collicles with

Subsequent maturation of a single dominant follicle

rapid maturation of the follicle and its estrogen production

rapidly rising plasma estrogen levels

(midcycle estrogen surge)

Positive feedback
a burst of GnRH secretion and increased responsiveness of
pituitary gonadotropes to GnRH

a burst of LH secretion

rapidly rising plamsmaLH levels (midcycle LH surge)

ovulation
corpus luteum formation and
luteal production of estrogen and progesterone

slowly rising plasma estrogen,

progesterone (and inhibin) levels
Negative feedback
Decreased secretion of FSH and LH and if there is no fertilization

Luteolysis

Diagrammatic summary of feedback control of ovarian cycle

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✓ Due to increased secretion of FSH and LH,
✓ development of a new crop of follicles with subsequent maturation of a single dominant follicle occur.
✓ Rapid maturation of the follicle produce estrogen. Midcycle estrogen surge (36-48 h before ovulation) gives
positive feedback to GnRH secretion.

✓ A burst of GnRH secretion and increased responsiveness of pituitary gonadotropes to GnRH lead to a burst
of LH secretion.
✓ Midcycle LH surge cause ovulation (9h after LH peak).
Then corpus luteum is formed
✓ and luteal production of oestrogen and progesterone occur. Slowly rising plasma oestrogen, progesterone
and inhibin levels give negative feedback to LH and FSH.

✓ Decreased secretion of FSH and LH occur and if there is no fertilization,

✓ luteolysis occur.
✓ Fall in plasma oestrogen and progesterone level occur due to luteolysis.

✓ Withdrawal of hormonal support leads to menstration and increased secretion of GnRH.

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Endocrine Functions of the Ovary
Ovarian Hormones:
1. Estrogens
2. Progesterone
3. Androgens (Androstenedione)
4. Inhibin
5. Relaxin (particularly during pregnancy)

Estrogens (Oestrogens) (C 18 steroids with benzene rings)

Principal Estrogens:
17 β – Estradiol (E2) – most potent
Estrone (E1) - in equilibrium in circulation with E2
Estriol (E3) - a metabolite of E1; least potent but becomes the principal estrogen during pregnancy

Sources:
1. Ovarian follicles
a. granulosa cells - secrete estrogens into the follicular fluid.
b. theca interna cells - secrete estrogens into blood circulation.
2. Corpus luiteum of menstruation (luteal cells)
3. Corpus luteum of pregnancy (early weeks)
4. Foeto-placental unit: takes over the function of corpus luteum after 6th week of pregnancy.
5. Adrenal cortex (both sexes)
6. Testes (Sertoli cells)
(Small amounts of estrogens are formed from androgens is the peripheral tissues such as
adipose tissue).

Effects of oestrogen
A. Effects of oestrogens in follicular fluid of ovarian follicle
Stimulate growth and maturation of ovarian follicle (together with FSH)
B. Effects of circulating oestrogens
1. Development and maintenance of female secondary sex characteristics at puberty and beyond
2. The follicular phase changes during the menstrual cycle
3. Continued growth of female secondary reproductive organs during the luteal phase and in
pregnancy
In general, estrogens cause growth of female reproductive organs and have actions on brain.
(1) Genital
- Endometrium (growth of endometrial glands, epithelium, increased vascularity and
stromal tissues) - menarche
- Myometrium (increase excitability & contractility)
- Uterine tubes (increase motility)
- Cervix (mucus - thin, alkaline, elastic & cervical smear - arborizing fern like pattern)
- Vagina (growth of vaginal epithelium which becomes cornified)

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 - Breast (proliferation of ducts, growth of nipple & pigmentation of nipple and areola)
(oestrogen = growth hormone of breast) – thelarche

(2) Extra genital

- Growth spurt
- Broadening of hip & pelvic girdle ( broad hip & narrow shoulder converge thigh&
diverge arm and widening of carrying angle)
- Deposition of fat in breast, buttocks and thigh
- Skin : soft & smooth
- Sebaceous secretion : more fluid, reducing acne formation
- Hair : more scalp hair & less body hair
- Growth of axillary and pubic hair ( flat top triangular pattern) - puberche
(3) Behavioral effects
Shy, sensitive, emotional, dependent, interest in opposite sex & increase libido
(4) Endocrine effect
1. (-) feedback on FSH
2. (-) as well as (+) feedback on LH
3. Stimulate secretion of prolactin and growth hormone
4. increased hepatic synthesis of
i. angiotensinogen
ii. plasma protein that transport thyroxine, cortisol and progesterone
(5) Others
1. Promote growth of long bone but cause epiphyseal closure
2. Lower cholesterol level & prevent atherosclerosis
3. Decrease osteoclast activity & prevent osteoporosis
4. antagonize stimulatory action of prolactin on milk secretion
5. Cause salt & water retention
6. Large dose of oestrogen promote thrombosis
7. rapidly produce vasodilation by increasing local production of NO

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Progesterone (a C 21 Steroid)
Sources:
1. Ovary:
luteal cells of corpus luteum of menstruation and corpus luteum of pregnancy
(early weeks)
(Note: cells in the ovarian follicle also secrete small amounts of progestrerone into
The circulation)
2. Placenta : syncytiotrophoblast
3. Adrenal cortex in both sexes and
4. Testes : small amounts

Effects of Progesterone:
Progesterone causes secretory (luteal phase) changes in female reproductive organs during the
menstrual cycle and periodic preparation for implantation of fertilized ovum. (pro = before; gestrerone =
gestation= pregnancy).
Progesterone also maintains pregnancy principally by decreasing oestrogen – induced myometrial
excitability and contractility.
It supports the secretory function of the breasts during lactation.

1. Effects on Uterus:
1.1 On endometrium: secretory changes in endometrial glands and stromal oedema;
decreases the number of estrogen receptors and increases the rate of conversion of E2 to
less active estrogens.
1.2 On myometrium: Anti-estrogen effect by decreasing excitability, and decreasing
sensitivity to oxytocin.
1.3 On cervical mucus: Thick, tenacious, cellular (unfavorable for sperm survival and
transport) cervical smear- fails to form fernlike pattern)

2. Effects on Vagina and Breast

2.1 vaginal epithelium: proliferation and secretion of thick mucus
2.2 breasts : progesterone stimulates the development of lobules and alveoli from estrogen-
prepared ductal tissue.

3. progesterone increases production of heat in the body (thermogenic effect)

(rise in basal body temperature following ovulation)
4. Progesterone stimulates respiratory centre and increases pulmonary ventilation. The alveolar
PCO2 falls in pregnancy.
5. Progesterone exerts negative feedback effect at both the pituitary and hypothalamic levels. In
large doses, it inhibits LH secretion and poteniates the inhibitory effect of estrogens, preventing
ovulation (large doses progeterone are used as contraceptive).

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