Physiology of Female reproductive system

Dr. Ehsan Saboory

Professor of Physiology

Dep. of physiology, Faculty of medicine, Urmia University of medical scinces

Anatomy of Female Reproductive System

• Female reproductive organs• Ovaries

• Uterine tubes

• Uterus

• Vagina

• External genital organs

• Mammary glands

Uterus, Vagina, Uterine Tubes, Ovaries and Supporting Ligaments

Ovary Histology

Physiology of the Female Reproductive System

• Oogenesis (meiosis in females)

• Follicle Development

• each month one follicle develops into a secondary oocyte released via ovulation

• ca. 500 released during reproductive life (from a potential 400,000 primary oocytes)

Maturation of Follicle and Oocyte

Ovarian Cycle - Follicular Phase• Ovarian follicle (immature oocyte - actual cell

undergoing meiosis)

• surrounding cells: Follicle Cells, after proliferation into several layers: Granulosa Cells - connected to oocyte via gap junction (supply of ions, nutrients & signaling molecules)

• layer of connective tissue gives rise to Thecal Cells: synthesize androgens - Granulosa Cells convert into estrogens, and secretion of glycoproteins forming Zona Pellucida

Ovarian Cycle - Luteal Phase

• After ovulation - Granulosa & Thecal Cells form Corpus Luteum secreting progesterone and small amounts of estrogen

• If no fertilization occurs - degeneration after 10 days (corpus albicans)

• If fertilization occurs - embryonal hormones cause continued secretion of progesterone for 3 months (then placenta continues progesterone production)

Maturation and Fertilization of Oocyte

Gametogenesis

• Oogenesis• Results in formation of secondary oocyte

which is released during ovulation• If no fertilization occurs, meiosis II will not occur.

• Stages of oogenesis1. Oocytogenesis

– Forms oögonia– During fetal development starting at week 10 and

completing around birth– Results in formation of primary oocytes (~1/2 million)

1. Ootidogenesis– Results in the formation of secondary oocytes– These are dictyate in prophase I

1. Formation of ovum (if fertilization occurs)

The Basics

Gametogenesis

Gender Determination• Chromosomes determine gender

• 23 donated by egg (n)• 23 donated by sperm (n)

• Syngamy• The fusion of gametes to form a zygote• Consists of

• plasmogamy– union of cell membranes and cytosol

• Karyogamy– union of genetic material– Autosomes: 44 or 22 pair– Sex chromosomes: 2 or 1 pair

• XX chromosomes = female• XY chromosomes = male

What happens if karyogamy of sex chromosomes is different?

Gender Determination

• Non-disjunction during meiosis I or II• Monosomy or polyploidy

• XO (no Y chromosome, or second X)

• Turner’s syndrome– Phonotypical female

What about YO monosomy?

Gender Determination• Non-disjunction during meiosis I or II

• Polyploidy• The incomplete separation of homologues during meiosis results in

a zygote with too many chromosomes• Regarding the sex chromosomes, it may be

– XXY (47 chromosomes total)• Male sex organs; unusually small testes, sterile. Breast

enlargement and other feminine body characteristics. Normal intelligence.

– XYY• Individuals are somewhat taller than average and often have

below normal intelligence. At one time (~1970s), it was thought that these men were likely to be criminally aggressive, but this hypothesis has been disproven over time.

• XXYY – male and very rare (48 chromosomes)

– XXX (Trisomy X)• Individuals are female normal, undistinguishable except for by

karyotype.

Gender Determination

• The embryo exhibits gender bipotential• Around week seven of fetal development the SRY

(Sex-determining Region of Y chromosome) gene becomes activated

• The SRY directs the bipotential gonads

• The absence of this on the X chromosome causes the gonads to develop into ovaries

– Ovaries then produce further gender biased hormones

• The presence of this gene and its products causes the gonads to descend and develop into testes

– Testes then produce further gender biased hormones– Translocation of the gene to X chromosome results in an XX

individual (genotype) but with XY characteristics (phenotype)

Functioning of Female Duct System• After ovulation ovum is released into peritoneum

• no enclosed connection of ovaries and tubes

• possible entry of pathogens in to cavity – PID: Pelvic Inflammatory disease

• fimbriae are covered with beating ciliae that sweep the ovum into the tube

• sometimes fails, ovum lost in peritoneum, possible ectopic pregnancy - natural abortion

• ovum moved by cilia & muscular contractions along tube - fertilization

Uterus

• Hollow thick-walled organ

• Bulk - smooth muscle in myometrium

• Cervix - narrow neck part - produces mucus via cervical glands - lubricates the vagina

• cervical mucus changes consistency during cycle (less viscous in mid-cycle facilitating sperm entry)

• Cervical Cancer (relatively common) Pap smear

Vagina• Highly extensible, hollow organ

• fibroelastic adventitia, smooth muscle, mucosa

• stratified, sqamous epithelium (withstand mechanical friction)

• release of glycogen - metabolized by vaginal flora to lactic acid (anaerobic metabolism), pH = 4

Mammary Glands

• Present in both sexes (only functional in females)

• modified sweat glands, part of the integumentary system

• glandular structure underdeveloped outside of pregnancy - full development only in late pregnancy (lactation)

• size in non-pregnant women due to adipose tissue

Mammary Glands

• Organs of milk production located within mammae or breasts

Breast Cancer

• Very common: most common cancer in women ca. 1/8 in developed countries

• Risk factors:• early onset of menses, late menopause, no

pregnancies or later in life

• genetic predisposition: BRCA1, BRCA2 genes• 10% of cases

• 70% no risk factor

• yearly mammography early diagnosis

Puberty and Menstrual Cycle

• Puberty

• Begins with menarche or first episode of menstrual bleeding

• Begins when GnRH levels increase

• Menstrual Cycle

• About 28 days long

• Phases• Menses

• Proliferative phase

• Secretory phase

• Menses

• Amenorrhea: Absence of a menstrual cycle

• Menopause: Cessation of menstrual cycles

Menstrual Cycle

Hormone Regulation during Menstrual Cycle

Female Reproductive PhysiologyBasics

• The hypothalamus-pituitary-gonad axis controls the required physiologic changes that occur both in the ovaries and in the uterus of the menstrual cycle.

• The Menstrual Cycle• Duration

• Approximately 28 days (ranges 24 – 35 days)• Starts with the removal of the endometrium & release of FSH by the

anterior pituitary

• The ovarian cycle• Development of ovarian follicle• Production of hormones• Release of ovum during ovulation

• The uterine cycle• Removal of endometrium from prior uterine cycle• Preparation for implantation of embryo under the influence of ovarian

hormones

Female Reproductive PhysiologyThe Cycles

• Three Phases of the Ovarian Cycle• Follicular phase• Ovulation phase• Luteal phase

• Three Phases of the Uterine Cycle• Menses• Proliferative Phase• Secretory Phase

• These ovarian and uterine phases are intimately linked together by the production and release of hormones

Female Reproductive PhysiologyThe Cycles

Hormonal control of the ovarian cycle

Female Reproductive PhysiologyThe Cycles

Hormonal control of the uterine cycle

Female Reproductive Physiology

All together

Female Reproductive PhysiologyFertilization Effects

• What happens if fertilization occurs?• Uterine endometrium is maintained by

• First the release of progesterone from the corpus lutem, • then the release of hCG (human chorionic gonadotropin) which

maintains the corpus luteum until the 7th week,• From 7th week on, the placenta produces progesterone which

continues to maintain the endometrium & the corpus luteum degenerates

– Placenta also produces estrogen and progesterone which at high levels blocks GnRH

• Estrogen is also involved in breast development• Progesterone is also involved in uterine maintenance and

relaxation (prevents premature contractions)• Placenta also produces hPL (human placental lactogen)

– Implicated in breast development and milk production• Though determined not the only factor as lack of hPL has no ill

effects– More important is the role hPL plays in fetal nutrition by altering

maternal glucose and fatty acid metabolism

Female Reproductive PhysiologyFertilization Effects

• What changes occur to allow parturition?• Increasing levels of corticotropin-releasing hormone

(CRH) from the placenta a few weeks prior to delivery• Early deliveries have been linked to early elevated levels of CRH • During delivery

– progesterone levels drop off– Oxytocin levels rise

• Oxytocin receptors on the uterus are upregulated during gestation

– Inhibin levels increase• Relax the cervix and ligaments of the pelvis• Allows for increased stretch of the cervix which triggers

additional oxytocin which triggers stronger uterine contractions which increase stretch of the cervix which triggers oxytocin which triggers stronger uterine contractions which increases stretch of the cervix which increases oxytocin release which increases uterine contractions which increases stretch on cervix which….

Female Reproductive PhysiologyOne Possible Outcome

Female Reproductive PhysiologyOr….

Female Sexual Behaviorand Sex Act

• Female sexual behavior

• Depends on hormones

• Androgens and other steroids

• Depends on psychological factors

• Female sex act• Parasympathetic

stimulation• Blood engorgement

in clitoris and around vaginal opening

• Erect nipples• Mucouslike fluid

extruded into vagina and through wall

Female Fertility and Pregnancy

• Female fertility• Sperm ejaculated into vagina

during copulation and transported through cervix and uterine tubes to ampulla

• Sperm cells undergo capacitation

• Pregnancy

• Oocyte can be fertilized up to 24 hours after ovulation

• Sperm cells can be viable for up to 6 days in female tract

Sperm Cell Movement

Changes in Hormones During Pregnancy

Contraception

• Behavioral methods• Abstinence

• Coitus interruptus

• Rhythm method

• Barrier methods• Condom

• Diaphragm

• Cervical cap

• Spermicidal agents

• Lactation

• Chemical methods• Oral contraceptives

• Injections as Depo-Provera

• Implants

• Morning-after pills

• Surgical methods• Vasectomy

• Tubal ligation

• Abortions

Contraception• Male: Vasectomy – ambulantory surgery

(permanent sterility)

Contraception

• Female: Tubal Ligation

Effects of Aging

• Male

• Decrease in size and weight of testes

• Decrease in sperm production

• Prostate gland enlarges and increase in cancer

• Impotence is age-related

• Decrease in sexual activity

• Female

• Menopause

• Decrease in size of uterus and vaginal wall thins

• Age related increase in breast, uterine, ovarian cancer

Sexually Transmitted Diseases STDs

• Most significant cause for reproductive disorders (incl. Sterility)

• Gonorrhea• Neisseria Gonorrhea (penicillin, tetracycline)

• Syphilis• Treponema pallidum (lethal to fetus) (penicillin)

• Chlamydia• Chlamydia trachomtais (most wide spread STD)

(tetracycline)

Sexually Transmitted Diseases STDs

• Vaginitis (local infection)• caused by: Trichomonas vaginalis (protozoan,

metronidazol treatment), Gardnerella vaginalis (bacterium), Candida (fungus, clotrimazol treatment)

• Genital Warts• caused by a large group of papilloma viruses

• risk factor for cancer (esp. cervical cancer)

• cryosurgery, laser surgery, alpha interferon

Sexually Transmitted Diseases STDs

• Genital Herpes• caused by: Herpes Simplex or Epstein-Barr

Virus

• severe malformation of fetus

• latent infection (very wide spread ?)

• difficult treatment (acyclovir)

Development of Reproductive System

• Sex Determination• Sex Chromosome - Y Chromosome - SRY gene

(transcription factor) initiates testes development in embryo - production of androgens relatively high during fetal development - morphogenesis of male sex organs - final maturation & development in puberty

• if SRYabsent (default development as female)

• if any gene leading to final stage is defective many possible aberrations of sexual development

Sex Determination

• Chromosomal Non-disjunctions cause sexual abnormalities• e.g.: XO Turner Syndrome (no ovaries)

• YO lethal in utero

• more than XX: underdeveloped ovaries, limited fertility, mental retardation (>4X)

• XXY Kleinfelter Syndrome (1/500 males) sterile

• XYY Normal males

Vaginal Cytology in animals with estrous Cycles

• The vaginal epithelium is responsive to sex steroids, particularly estrogen, and undergoes predictable changes through the cycle in response to changes in blood concentrations of ovarian hormones. Rising levels of estrogen cause the vaginal epithelium to become "cornified" - the surface cells become large and flattened, with small or absent nuclei.

Proestrus – Estrus – DiestrusVaginal Cytology