Female Reproductive System

Where does fertilization commonly take place?

Within the ampulla of the fallopian tube → takes around 5-6 days to travel through the isthmus to the uterus, then implanting if fertilizing.

Puberty

• begins at age 8-10 for most girls

• triggered by rising levels of GnRH which stimulate anterior lobe of pituitary to produce FSH and LH

  • requires sufficient leptin (fat percentage) to happen

• Thelarche: development of breast

• Pubarche: appearance of axillary and pubic hair with apocrine sweat glands/sebaceous glands, libido

  • driven by androgens from ovary and adrenal cortex

• Menarche: first menstrual period ~12

• Female hormones secreted cyclically and in sequence

Ovarian cycle vs Uterine cycle

Ovarian → changes in ovary during and after maturation of oocyte

Uterine → preparation of uterus to receive fertilized ovum

if implantation does not occur, stratum functionalis is shed during menstruation

Aging female reproductive cycle

• Hormone directed sexual characteristics start to develop at puberty

• Reproductive cycle occurs once/month from menache until menopause

  • fertility declines with age

  • menopause is cessation of menstruation with fewer than 1000 follicles to stimulate hormone secretion and low estrogen and progesterone cause atrophy in the uterus and breasts and vagina

Oogenesis

• mitosis of oogonia before birth

• 6-7 million oogonia reduced to ~2 million primary oocytes by atresia

• By puberty ~ 200,000 primary oocytes remain

• Only 400~ secondary oocytes ovulated

  • meiosis I completes just before ovulation

• secondary oocyte completes meiosis only if fertilized

Folliculogenesis

• As oogonia become primary oocytes, primordial follicles develop

• cohorts of 1-2 dozen primordial follicles recruited each month

• recruitment turns follicles into primary follicles with granulosa cells

• primary follicles develop into secondary follicles

  • thecal cells convert cholestrol into androgens (LH) and granulosa cells convert that into estrogens (FSH)

• tertiary follicles are antral follices which develop follicular fluid, corona radiata, and cumulus oophorus

• mature follicle is ovulated

• granulosa cells: convert androgens into estrogen under influence of FSH

• theca cells: convert cholesterol into androgens under influence of LH

Oogenesis steps

1. Oogonium (2n) undergoes mitosis to create a primary oocyte (2n).

2. Primary oocyte goes through meiosis I to create secondary oocytes.

   • It produces a haploid secondary oocyte and a haploid first polar body (degenerates and is reabsorbed).

   • the secondary oocyte is formed before ovulation and is arrested in meiosis II until fertilized.

3. After ovulation, if sperm is present and fertilization takes place, the secondary oocyte continues into meiosis II.

4. Only secondary oocytes undergo meiosis II.

5. An ovum and second polar body form. The ovum becomes a diploid zygote when it unites with the sperm.

Hormonal regulation of the sexual cycle

• GnRH controls the female reproductive cycle

  • stimulates anterior pituitary to secrete FSH and LH

• FSH initiates growth of follicles that secrete estrogen → estrogen maintains reproductive organs

• LH stimulates ovulation and promotes formation of the corpus luteum which secretes estrogens, progesterone, relaxin, and inhibin

• progesterone prepares uterus for implantation and the mammary glands for milk secretion

• Relaxin facilitates implantation in the relaxed uterus

• Inhibin inhibits the secretion of FSH

Hormonal Regulation Chart

Sexual cycle

• averages 28 days but ranges 20-40 days

• Hormone cycle produces hierarchy of control

  • hyopthalamus → pituitary → ovaries → uterus

• Follicular phase (2 weeks)

  • menstruation occurs during first 3 to 5 days of cycle

  • uterus replaces lost endometrium and follicles grow

• Luteal phase (2 weeks)

  • corpus luteum stimulates endometrial thickening

  • endometrium lost again if pregnancy does not occur

Ovarian cycle and Menstrual Cycle

Estrogen

Released by: the ovaries or corpus luteum

• Dominates the proliferative phase where it builds the endometrium

• promote development and maintenance of female reproductive structures, feminine secondary sex characteristics, and breasts

• Increases protein anabolism

• lowers blood cholesterol

• moderate levels inhibit release of GnRH, FSH, and LH

Low Estrogen Levels → Stimulates GnRH and FSH

Low estrogen occurs at the very start of the menstrual cycle (during menstruation), because the previous cycle's corpus luteum has just degraded and stopped producing hormones.

• Because there is almost no estrogen in the bloodstream, the "brakes" on the brain are completely removed → The hypothalamus freely releases GnRH which commands the anterior pituitary to secrete FSH → FSH is needed to recruit immature ovarian follicles and start the next cycle

• Big idea: Low estrogen stimulates (GnRH and FSH)

Moderate Estrogen Levels → Inhibits FSH and Stabilizes LH

As those new cohort of follicles grow, their granulosa cells begin secreting estrogen. By the mid-follicular phase, estrogen reaches moderate, steady levels.

• Moderate estrogen binds to estrogen receptors on the hypothalamus and pituitary. It signals the brain to dial back FSH production → Method used to select the dominant follicle which will have the most FSH receptors, meaning it can survive on lower amounts of FSH

• The smaller, less-developed follicles are starved of FSH and wither away, ensuring that usually only one egg matures.

• Big Idea: Moderate estrogen levels inhibit FSH

High Estrogen Levels → Stimulates a Massive LH & FSH Surge

By the end of the follicular phase, that single dominant follicle grows massive and becomes an estrogen-producing powerhouse, driving blood concentrations to peak levels.

• When estrogen passes a high threshold and stays there for at least 36 to 48 hours, it activates the hypothalamus → Triggers the dumping of GnRH → creates the explosive LH surge (and a smaller FSH bump) and forces ovulation.

• Big Idea: High estrogen stimulates FSH and LH surge to trigger ovulation

Progesterone

• Dominates the secretory phase

• Stops the growth (proliferation) → alters the endometrium to secrete more glycogen, proteins, and lipids to welcome an embryo.

• Prepares mammary glands to secrete milk

• Inhibits release of GnRH and LH → no more making new follicles if there is an ovulated follicle that can become fertilized

• Tells spiral arteries to stop contraction → more blood flow

Proliferation

Endometrium grows thicker

Relaxin

• Inhibits contractions of uterine smooth muscle

• Increases flexibility and dilates cervix during pregnancy

Inhibin

• Inhibits release of FSH and to a lesser extent LH

• It is secreted by the granulosa cells of the developing ovarian follicles (and later by the corpus luteum)

• inhibin acts directly and exclusively on the anterior pituitary. It tells the pituitary to stop secreting FSH, without affecting LH or GnRH → allows for dominant follicle to grow

Ovarian cycle

Follicular phase:

• 2 weeks

• menstruation occurs during first 3-5 days of cycle due to low progesterone

• grow a mature egg and rebuild the uterine lining.

Steps:

1. The hypothalamus starts releasing GnRH, which signals the anterior pituitary to secrete FSH → FSH travels to the ovaries and "recruits" a small cohort of about 15–20 immature follicles to begin growing

2. Next, granulosa cells surrounding the eggs start producing moderate levels of estrogen and inhibin to turn down FSH and pick the dominant follicle (most FSH receptors

3. The dominant follicle releases massive amount of estrogen which then passes a threshold and triggers hypothalamus to release burst of GnRH

4. Pituitary becomes hyper-sensitive to to GnRH → triggering the explosive LH surge (alongside a smaller bump in FSH).

Luteal Phase

• 2 weeks

• The corpus luteum forms after ovulation → immediately starts pumping out massive amounts of progesterone and moderate amounts of estrogen → progesterone brings more nutrients and vascularization to the endometrium

• Keeps ovaries suppressed by telling brain to stop GnRH, FSH, and LH release

• endometrium lost again if pregnanacy does not occur

Menstrual Cycle

Menstrual Phase:

• Lasts for 5 days

• In ovary:

  • 20 follicles that began to develop 6 days before are now beginning to secrete estrogen

    • fluid if filling the antrum from granulosa cells

• In Uterus:

  • declining levels of progesterone cause spiral arteries to constrict → stratum functionalis layer of endometrium is sloughed off due to necrotizing

Preovulatory phase:

• lasts from day 6-13

• In ovary (follicular phase):

  • follicular secretion of estrogen and inhibin has slowed secretion of FSH

  • dominant follicles survive to day 6

  • by day 14, dominant follicle has been selected and matures

  • increased estrogen levels by dominant follicle trigger the secretion of LH by anterior pituitary

• In uterus (proliferative phase):

  • increasing estrogen levels have repaired and thickened the stratum functionalis to 4-10mm in thickness

Ovulation → caused by elevated estrogen levels that stimulate release of GnRH which stimulates anterior pituitary to release LH (surge)

Postovulatory Phase:

• Lasts 14 days

• In the ovary (luteal phase)

  • if fertilization did not occur, corpus albicans is formed

  • as hormone levels drop, secretion of GnRH, FSH, and LH rise

  • If fertilization did occur, developing embryo secretes HCG which maintains health of corpus luteum and its hormone secretions

• In the uterus (secretory phase)

  • hormones from corpus luteum promote thickening of endometrium to 12-18mm

  • form more endometrial glands and vascularization

  • if no fertilization occurs menstrual phase will begin

LH

Made in the anterior pituitary and stimulated by GnRH released by hypothalamus

• LH binds to specific cells in the ovaries called theca cells on the outer layer of follicles → stimulates conversion of cholesterol into androgens → which granulosa cells will use FSH to convert into estrogen

• As the dominant follicle matures, it pumps out massive amounts of estrogen. Once estrogen levels cross a high threshold for 48 hours, it triggers an explosive, 10-fold spike in LH release from the pituitary gland—the LH surge

Preovulatory phase

• From Day 6-13

• In the ovary (follicular phase)

  • follicular secretion of estrogen and inhibin has slowed secretion of FSH

  • dominant follicles survives to day 6

  • by day 14, mature follicle has enlarged

  • increasing estrogen levels trigger LH secretion

• In the uterus

Amenorrhea

absence of menstruation

dysmenorrhea

pain associated with menstruation