Female Reproductive

Physiology

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Functions of female reproductive system

• Gametogenic- oogenesis

• Endocrinologic- hormonogenesis

• Reception of sperm

• Site of fertilization, or conception

• Pregnancy- Maintenance of developing fetus

• Parturition- giving birth

• Lactation- breast feeding

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Functional anatomy

• Gonads - ovaries

• Reproductive tract

✓ Oviducts, uterus, cervix &

vagina

• External genitalia

✓ Mons pubis, labia majora,

labia minora, clitoris, vestibule
of vagina & vestibular glands.

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Ovary
• A female gonad containing two zones:-
❖Cortex:- contains oocytes enclosed within follicles in various
stages of development.
✓Stroma b/n follicles consists supporting connective tissue &
interstitial cells.
❖Medulla:- Contains blood vessels, lymphatic vessels & nerves.

• Functions of ovary:
✓ Gametogenic function:- Oogenesis
✓ Endocrine function:- Hormonogenesis
o Steroidal - Estrogens, Progestins, Androgen
o Nonsteroidal - Relaxin, Inhibin
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Oogenesis
• Process through which mature female gamete is formed.

• Site:- Cortex of ovary & completed in oviduct.

• Onset:- Starts during fetal life, completed after puberty & continues
until menopause.

• Occurs monthly except during pregnancy.

• Development of oocytes occur in three stages:-

✓ Proliferation of oogonia by mitotic division to form 1° oocyte.

✓ 1° oocyte develop to 2° oocyte & 1st polar body by meiosis I.

✓ 2° oocyte develop to mature ovum & 2nd polar body by meiosis II.
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• During fetal life, all oogonia proliferate into 1° oocytes by mitosis.

• Meiosis I starts during fetal life but arrested in prophase.

✓ Completed during puberty just before ovulation to give 2° oocyte

& 1st PB.
o 2° oocyte receives almost all cytoplasm.
o 1st PB degenerates (meiosis II of PB may or mayn’t occur).

• Meiosis II begin after ovulation but arrested in metaphase.

✓ Completed if fertilization occur otherwise 2° oocyte degenerates.

✓ If fertilization occur mature ovum & 2nd PB will be formed.

o Mature ovum (fertilized oocyte) retain most of cytoplasm
o 2nd PB degenerates.
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Oocyte degeneration
• 7 million oogonia at 5th month of
gestation
↓
• 2 million 1° oocyte at birth
↓
• 300,000 1° oocytes during puberty
↓
• 400 - 500 2° oocytes ovulated during
a woman’s reproductive life
↓
• 99.9% of oocytes undergo atresia
during reproductive life of a woman.
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Follicular development (Folliculogenesis)

• Process by which follicles develop & mature.

• Oocytes grow throughout their life in ovarian follicles till ovulation.

• Ovarian follicle is the functional unit of ovary.

• Starts during intrauterine life & continues till ovulation.

• At the beginning of each menstrual cycle, some follicles recruited to

develop into large antral follicles.

• 1 week into the cycle, only one dominant follicle finally matures.

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Stages of follicular development

1. Primordial follicle

✓ Primary oocyte surrounded by single layer of granulosa cells.

2. Primary follicle

✓ Primordial follicles develop into primary follicles.

✓ Zona pellucida formed b/n granulosa cells & primary oocyte.

3. Secondary/preantral follicle

✓ Primary follicles develop into secondary follicles

✓ Granulosa cells divide & form several layers.

✓ Early theca cell is formed at the periphery of basal lamina.

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4. Early tertiary/antral follicle

✓ Theca differentiates into theca interna & theca externa

✓ Granulosa cells secrete follicular fluid called antrum.

5. Graafian follicle

✓ Secondary follicle becomes mature (graffian) follicle.

✓ Only one dominant follicle, continues to develop, & other

follicles undergo atresia.

✓ Sometimes 2 or more follicles mature & more than one egg

may be ovulated resulting multiple births.

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 Process of oogenesis
& folliculogenesis

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Functions of theca cells
• Synthesize androgens & very small amount of estrogen &
progesterone.
• Provide structural support to growing follicle.
Functions of granulosa cells
• Nourish oocyte.
• Secrete chemical messengers that influence oocyte development.
• Secrete antral fluid.
• Secrete estrogen (from androgens of theca cells), progesterone &
inhibin.

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Sex hormone synthesis by granulosa & theca cells
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Formation of corpus luteum

• At ovulation, follicle ruptured by enzymatic degradation.

✓ 2° oocyte surrounded by corona radiata expelled.

• Ruptured follicle filled with blood → corpus hemorrhagicum.

• Blood replaced with luteal cells rich in lipid → corpus luteum.

✓ LH maintains its functions by promoting luteinization.
✓ Secretes progesterone, estrogen, inhibin & androgens.

• If fertilization does not occur, luteolysis → corpus albicans

(avascular & nonfunctional).

• If fertilization occurs, hCG maintains luteinization till placenta

becomes functional. 15
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Menstrual cycle
• Monthly cycle of changes in ovary & uterus.

• Onset:- starts at puberty & continue until menopause.

✓ Menarche: woman’s first menstruation.

• Duration:- Variable (21-35 days, average = 28 days).

• Cause:- Cyclic rise & fall in female reproductive hormones.

• Purpose:- Periodic preparation for fertilization & pregnancy.

❖ Ovarian cycle ❖ Uterine cycle

✓ Follicular phase ✓ Proliferative phase
✓ Ovulatory phase ✓ Secretory phase
✓ Luteal phase ✓ Menstrual phase 17
Ovarian Cycle
• Cyclical changes in ovary during & after maturation of the
follicle & oocyte.
Follicular (preovulatory) phase
• 1st day of menses upto ovulation [1st - 13th day].
• More variable in length [14±7 days].
• Dominant ovarian hormone is estrogen.
• Follicular growth, maturation & dominance.
• Changes in ovary are under influence of FSH.
• Estrogens & inhibin of dominant follicle decrease FSH causing
other follicles to stop growing.
Ovulatory Phase
• Rupture of mature (graffian) follicle & release of 2° oocyte.

• Occur at day 14 of 28-day cycle.

• Markers of ovulation:

✓ Mittelschmerz: Fleeting lower abdominal pain.

✓ Spinnbarkeit: ↑ Elasticity of cervical mucus.

✓ Ferning pattern of cervical mucus due to crystallization of NaCl.

✓ ↑ Body temperature ( 0.5°C).

✓ Vaginal discharge (spotting)

❖ Few postmenarchal & perimenopausal periods are anovulatory.

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Events during ovulation
• LH surge & ovulatory peak of FSH.
✓ High levels of estrogens exert a positive feedback.
o Estrogen reaches its peak 2 days before ovulation.
o LH secretion ↑ 6-10 fold & peaks about 16 hrs before ovulation.

o FSH secretion also ↑ 2-3 fold 2 days prior to ovulation.

• Rapid swelling of the follicle caused by FSH & LH.

• Formation of stigma:- stretching form a thin avascular area.

• Release of proteolytic enzymes from theca cells.

• Enzymatic dissolution of follicular wall & degeneration of stigma.

• Rupture of graafian follicle & release of 2° oocyte.
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-ve feedback by estrogen during + ve feedback by estrogen during
follicular phase ovulatory phase 21
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Luteal (postovulatory) phase
• Interval between ovulation & menstrual flow (15th - 28th day).
• Duration is constant: 14 days.
✓ Day of ovulation = Length of menstrual cycle – 14 days
• Predominant ovarian hormone: Progesterone.
• Formation of corpus luteum under the influence of LH.
✓ Functions of CL:-
o Secretes hormones.
o Provide endocrinal environment for implantation.
o Maintains early part of pregnancy.
❖ What is the fate of corpus luteum?
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Uterine/endometrial cycle
• Cyclical preparation of the uterus to receive fertilized ovum.
Proliferative Phase
• Begins with the last days of menses (5th - 13th day).
• Dominant ovarian hormone: estrogen.
• ↑Growth of epithelial & stromal cells.
• ↑Mitosis of stratum basale which regenerates stratum functionale.
• Angiogenesis: neovascularization, lengthening of the vessels.
• Cervical epithelium secrets a watery mucus.
• Maturation of vaginal basal cells.
• Estrogen & progesterone receptors on endometrial cells.
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Secretory Phase
• Duration: 14th - 28th day.
• Predominant hormone: progesterone.
• Secretory changes in endometrium → for implantation.
✓ Mucous glands: Elongation & coiling.
o Secrete clear, thick viscous fluid containing glycogen
(Uterine milk).
•  Adhesivity of surface epithelium.
• Spiraling of blood vessels, ↑ vascularity.
• Cervical mucus becomes thick.
•  Number of estrogen & progesterone receptors.
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Menstrual Phase
• Periodic shedding of stratum functionale of endometrium.
• Duration: 1st - 4th day.
• Cause: Withdrawal of estrogens & progesterone.
✓ Stimulate release of prostaglandins causing uterine spiral
arterioles to constrict → cause menstrual cramps.
✓ Necrosis is initiated in the endometrial blood vessels, due to:
• Vasospasm
• Decrease nutrients to endometrium
• Loss of hormonal stimulation

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• Menses is composed of:
✓ Blood from ruptured blood vessels
✓ Mucin from glands
✓ Fragments of endometrial tissue
✓ Unfertilized egg
• Characteristics of menses:
✓ Duration:- 2-8 days (variable).

✓ Vol. blood loss:- 20-150ml (average 50ml).

✓ Type of blood flow:- 75% arterial, 25% venous.

✓ No clot formation b/c of fibrinolysin.

✓ Leukocytes released; uterus become resistant to infection.

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Disorders of menstruation
• Amenorrhea:- absence of menstrual period.
✓ Primary amenorrhea:- menstrual bleeding has never occurred.
✓ Secondary amenorrhea:- cessation of cycles in a woman with
previously normal periods, caused by:
o Pregnancy (most common cause)

o Emotional instability & changes in environment

o Hypothalamic diseases ( GnRH pulses)

o Pituitary disorders

o Primary ovarian disorders & systemic disease

• Menorrhagia:- heavy menstrual flow.

• Metrorrhagia:- irregular & prolonged menstrual flow.
• Dysmenorrhea:- painful periods.
• Oligomenorrhoea:- scanty & irregular periods. 29
Hypothalamic pituitary ovarian axis

• GnRH stimulates release of FSH & LH.

• FSH initiate follicular growth & stimulate estrogen secretion.

• LH - Stimulate further development of follicles & estrogen secretion.
- Stimulate thecal cells to produce androgens.
- Triggers ovulation.
- Promotes formation of corpus luteum.
• Estrogen has positive or negative feedback effect on GnRH &
gonadotrophins release depending on stage of the cycle.

• Progesterone, in presence of estrogen, inhibit secretion of GnRH.

• Inhibin inhibit secretion of FSH & to lesser extent LH.

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Ovarian Hormones & their physiologic effects

Estrogens
• 17β-estradiol, estrone, estriol (E2, E1, E3)
✓ Relative potency: E2 > E1 > E3

• Origin:-

✓ Ovary: granulosa cells & theca cells

✓ Corpus luteum

✓ Placenta

✓ Adrenal cortex

✓ Testis (Sertoli cells).

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Physiological effects of estrogen
Reproductive effects:

• Ovary: Stimulates growth of ovary & follicles.

• Uterine tubes: Contractions & ciliary activity.

• Uterus: - Myometrial contractions & responsiveness to oxytocin.

- Induces expression of progesterone receptors.

- Proliferation & vascularity of epithelial & stromal cells.

• Cervix: stimulates production of thin, watery & alkaline mucus.

• Vagina: proliferation of epithelial cells, glycogen deposition & ↓pH.

• Inhibits prolactin’s milk-inducing action on the breasts. 33

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• Development of female secondary sexual characteristics:

✓ Growth of external genitalia.

✓ Growth of breast particularly ducts & fat deposition.

✓ Female body configuration: narrow shoulders, broad hips &

female fat distribution.
✓ Less body hair/more scalp hair &  pubic hair pattern.
✓ High-pitched voice/no protein synthesis.

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Nonreproductive effects:

• Bone: Stimulates bone growth & ultimate cessation of bone growth

(closure of epiphyseal plates) → protects against osteoporosis.
• Liver: HDL, LDL→ Protects against atherosclerosis.
• CVS: Promotes vasodilation & inhibits platelet activation.
• Integument:  Fluidity of sebaceous gland → inhibition of acne.
• CNS: Neuroprotective (angiogenesis → inhibits neural cell death).
• Kidneys: Stimulates fluid retention.
• Adipose tissue: Deposition of fat in subcutaneous tissues but
↓visceral fat deposition.
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Progestins
• Progesterone
• 17α-hydroxyprogesterone
• Origin:
✓ Ovarian follicle
✓ Corpus luteum
✓ Placenta
✓ Adrenal cortex
✓ Testes

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Physiological effects of progesterone
• Secretory activity & vascularization of endometrium
• Decreases contractions of uterine tubes & myometrium.

• Induces thick, sticky cervical mucus.

• Decreases proliferation of vaginal epithelial cells.

• Stimulates breast growth, particularly glandular tissue.

• Inhibits milk-inducing effects of prolactin.

• CNS depressant effect (Premenstrual dysphoria)

• H2O retention, natriuretic (blocking action of aldosterone).

• Motility of intestine → constipation.

• Basal body temperature (0.50C, index of ovulation). 38
Relaxin

• Produced by corpus luteum.

• Relaxes uterus by inhibiting contraction of myometrium.

• At end of pregnancy, increases flexibility of pubic symphysis &

dilates uterine cervix.

Inhibin

• Secreted by granulosa cells & corpus luteum.

• Inhibits secretion of FSH & to lesser extent LH.

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Testosterone in females
• Significance
✓ Maintenance of sexual drive.
✓ Stimulation of growth of pubic & axillary hair.
• Abnormally large quantities of androgen → Virilism
✓  Body & facial hair (hirsutism).
✓ Irregularities of menses.
✓ Acne.
✓ Clitoromegaly.
✓ Muscle hypertrophy.
✓ Bitemporal balding.
✓ Breasts diminish in size. 40
Menopause
• Complete cessation of menstrual cycle.

• Occurs in all women as they age.

• Period of female climacteric during which reproductive cyclicity

gradually disappears.

• Mean age: 50 (45 – 55) years

• 12 consecutive months of amenorrhea.

• Cause: ↓ number of ovarian follicles & their unresponsive to

gonadotropins.

✓ Loss of follicular development.

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Hormonal changes during menopause:
• ↓ Estradiol & progesterone
• ↑ Gonadotropins (↑ FSH, ↑LH) due to negative feedback effect of
decreased sex steroids & inhibin
✓ Ratio FSH to LH >1 (before menopause; LH: FSH >1)
• Estrone (primary estrogen produced in adipose tissue)
✓ Predominant form of estrogen in postmenopausal women.
• ↑ Androgens:
✓ Preventing vulvar atrophy.
✓ Producing continued sex drive & response
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Features of menopause
• Result primarly from estrogen deficiency.
✓ ↓ Size of ovary & uterus.

✓ Vaginal epithelium atrophies, becomes dry & ↑ pH.

✓ ↓ Vaginal lubrication → ↓ coital frequency → ↓ Sexual act (All

phases of sexual act are affected).

✓ Easily traumatized skin & ↓ subcutaneous fat of the vulva.

✓ ↓ Glandular & ↑ fibrous tissues of the breast.

✓ Bone resorption → ↓ bone mass & strength → osteoporosis.

✓ ↑ Body T⁰ → peripheral vasodilation & sweating → hot flashes.

✓ Psychological symptoms (depression, insomnia, nervousness).

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Physiology of female sexual act
• Normally female is a passive partner during sexual intercourse.

• Sexual response in females has four phases like males:

✓ Excitement, Plateau, Orgasm & Resolution

• Tactile, visual, olfactory & auditory stimuli leads to excitement.

• Like males, arousal is controlled by parasympathetic stimulation.

✓ Increased blood flow to breast, external genitalia & vaginal wall.

o Engorgement of breasts & erection of nipples.

o Increased diameter & length of clitoris.

✓ Vestibular glands secrete mucus that also helps in lubrication.

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• Sexual gratification culminates in orgasm.

✓ Due to increased epinephrine secretion into the circulation.

• Increased skeletal muscle activity, increased HR & BP.

• Rhythmic peristaltic contractions of uterus & vaginal wall.

o Facilitates sperm transport

✓ There is no female counterpart to ejaculation.

✓ Female orgasm is not required for fertilization.

• Females do not become refractory following an orgasm.

✓ Can experience multiple orgasms.

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