Topic 5: Female Reproductive System- 2

Internal genitalia

ovaries

Accessory organs

Uterine tubes (oviducts), uterus, vagina

External genitalia

vulva

Function of female reproductive system

• produce gametes & hormones

• prepare to nurture developing embryo

Ovaries

• anchored by ligaments

  • ovarian, suspensory, mesovarium

• NB: the mesovarium is part of the broad ligament that supports the ovaries, oviducts and uterus

• served by ovarian arteries (branches of the abdominal aorta) plus ovarian branch of uterine arteries

Tunica albuginea

covering external surface of the ovary

Germinal epithelium

final outer covering of ovary

Ovarian cortex

• contains follicles at all stages of development

  • oocyte

  • granulosa cells

  • theca cells

Corpus luteum

formed from ovulated follicle each month

• prominent at 2nd half of menstrual cycle

• no baby- degrades

• baby- stays for first 3 months of pregnancy

Oviduct

• receive the egg & provide the site for fertilization; ~ 10 cm long

• oocyte released into peritoneal cavity → fimbriae direct it into ampulla of oviduct

• structure of wall of oviduct also helps oocyte move toward uterus:

  1) smooth muscle

  2) epithelial cells (lined with cilia)

  • external covering = visceral peritoneum; supported by the mesosalpinx

What is the isthmus?

bridge between the oviduct and uterus

Uterus

• anterior to rectum & postero-superior to bladder

• receives, retains, nourishes embryo

• shape of an inverted pear in nulliparous women

nulliparous women

women never pregnant before

internal os

uterus to cervix

external os

cervix to vagina

cervical glands

mucus fills cervical canal & covers the external os → prevents infection; less viscous at midcycle to:

• regulate by hormones

• less of a barrier to get pregnant

• promote fertility

The many supports of the uterus:

• mesometrium: laterally (broad ligament)

• cardinal (transverse cervical) ligaments: from cervix & upper vagina to lateral walls of pelvis

• uterosacral ligaments: to sacrum posteriorly

• round ligaments: to anterior body wall

Uterine Wall

• 3 layers:

  • perimetrium: = visceral peritoneum

  • myometrium: middle, interlacing bundles of smooth muscle

  • endometrium: simple columnar epithelium + thick lamina propria

    • stratum functionalis: closest to lumen

    • stratum basalis: deeper

vascular supply of uterus

• uterine arteries (from internal iliacs)

• to arcuate arteries

• radial arteries within myometrium

• straight arteries (stratum basalis) or spiral arteries (stratum functionalis)

Cause for uterus lining to shed

Spiral artery constriction

Vagina structure

• thin-walled tube, 8-10 cm long

• urethra is anterior and runs parallel

• no glands; lubrication provided by cervical glands

• epithelial cells store glycogen and are shed → metabolized to lactic acid by resident bacteria → acidic pH deters infection, but is hostile to sperm

Vagina is a passageway for:

• entry of sperm

• exit of menstrual flow

• delivery of infant

3 layers of the vagina

• adventitia: outer, fibroelastic

• muscularis: smooth muscle

• mucosa: inner, transverse rugae; stratified squamous epithelium

Hymen

Incomplete vascular partition of mucosa near vaginal orifice; of variable durability; can rupture during first sexual intercourse, but also can be ruptured by sports, inserting tampons, even pelvic exams

External Genitalia

• vulva: mons pubis, labia, clitoris, structures associated with vestibule

• mons pubis: fatty, rounded area overlying pubic symphysis; covered with hair

• labia majora: elongated, hair-covered fatty skin folds (homologue of scrotum)

• labia minora: thin, hair-free skin folds enclosed by labia majora

• vestibule: recess between labia minora - contains openings of urethra, vagina, & greater vestibular glands (homologous to bulbourethral glands)

• clitoris: erectile tissue (homologous to penis); hooded by skin fold; richly innervated; corpora cavernosa but no corpus spongiosum

Ovaries have 2 key functions

• produce oocytes

• produce reproductive hormones (eg: estradiol, progesterone)

• Remember:

  • the hormones a cell produces depends on the enzymes it has

  • steroids are lipids – can easily traverse PMs

Estradiol synthesis

CHOLESTEROL

progesterone

androstenedione

testosterone

estradiol

3 types of steroid hormones produced in the ovarian follicle

• progestins

• androgens

• estrogens

Progestins

• (eg: progesterone - all have 21 carbons)

• produced by all major ovarian cell types: follicular granulosa cells, theca cells, corpus luteum

• most important as a product of the corpus luteum - during luteal phase of menstrual cycle & for maintenance of pregnancy

Androgens

• (eg: testosterone - all have 19 carbons)

• most important as a precursor for synthesis of estradiol

• synthesized by follicular theca cells and by corpus luteum

• too much testosterone is associated with follicular atresia

Atresia

testosterone buildup causes degeneration of follicle

Estrogens

• synthesized by follicular granulosa cells and the corpus luteum

• essential for stimulation of follicular development, onset of puberty, etc.

• (eg: estradiol - all have 18 carbons)

Anterior Pituitary Hormones

• FSH

• LH

FSH

• Follicle-Stimulating Hormone

• stimulates ovarian follicles to grow & produce estradiol

LH

• Luteinizing hormone

• stimulates testosterone production by theca cells

• stimulates ovulation, secretion of steroid hormones by corpus luteum

• released from anterior pituitary glands

Hypothalamus hormones

GnRH (gonadotropin-releasing hormone)

GnRH

• Gonadotropin-releasing hormone

• Stimulates secretion of the secretion of both FSH & LH

• granulosa cells, like Sertoli cells, can produce inhibin

Primordial follicle

• oocyte + single layer of flattened granulosa cellsstarting point = oocyte surrounded by single layer of flattened follicular cells (will become granulosa cells)

• oocyte (primary oocyte) arrested at prophase of meiosis I

• by 6 months of age, ovary has full complement of primordial follicles

• ~2 million at birth; gradual loss (degeneration); ~400,000 remain by puberty

Initiation of development of primordial follicles does NOT require ______ stimulation - some follicles can and do begin developing at ____

gonadotropic; any time

At what stage are oocytes arrested? What would they look like under the microscope?

• prophase of meiosis 1

• would see chromosomes and mitotic spindles

What triggers the resumption of meiosis the first time?

1. LH surge

2. Fertilization

What is the fate of most primary oocytes??

never resume meiosis

What is the fate of most oocytes in which resumption of meiosis was initiated by trigger #1?

most aren’t fertilized (dont complete meiosis)

Ovarian follicular development

Oogonia t primary oocytes accomplished by birth

Primary Follicle: Developmental Events

• gonadotropin-independent

  • oocyte increases in size & acquires a zona pellucida

  • granulosa cells start to divide & form several layers outside oocyte

  • outside the basement membrane, ovarian interstitial cells closest to the growing follicle differentiate to form theca cells

• throughout these changes called a primary follicle

  • continued maturation of this follicle requires FSH and LH

What is an antrum? Why is it important to have an antrum in a maturing follicle?

• is a fluid-filled cavity that develops within a mature ovarian follicle, also known as a Graafian follicle

• make it easier for ovulation to occur

Antral Follicle

a fluid-filled sac on the ovary containing an immature egg

Basement membrane divides follicle into 2 compartments

• inner granulosa cell compartment

• outer theca cell compartment

Inner granulosa cell compartment

• nonvascularized

• FSH-responsive:

  • granulosa cell proliferation (E)

  • granulosa cell E production

  • more FSH receptors

Outer theca cell compartment

• vascularized

• LH-responsive

  • T production for use by granulosa cells to make E

Theca cell and granulosa cell hormone production diagram

Theca cells dont have the enzyme (aromatase) to convert to estrogen so its needs to be transferred to granulosa cells where the enzyme is present to convert to estrogens

Timing is Everything!

• if development coincides with rising FSH levels at beginning of cycle → development will be supported - otherwise: follicular atresia

• for one follicle to become dominant, must convert potentially androgenic environment to estrogenic environment - otherwise: atresia!!

Emerging dominant follicle becomes the __________

• preovulatory follicle

• E levels rise rapidly - FSH switches to inducing receptors for LH on granulosa cells (Why does this make sense? granulosa cells become corpus luteum (LH sensitive only)) → LH stimulates further E & P production stage is now set for LH surge to trigger ovulation

LH surge stimulates

1. resumption of meiosis - extrusion of polar body #1

2. P (progesterone) production by granulosa cells

3. increase in antral fluid volume

4. release of hydrolytic enzymes

Minor FSH surge

• ensures sufficient LH receptors for luteal phase

• stimulates synthesis of hyaluronic acid - important in cumulus expansion (let go of tight junctions, help pull oocyte off)

What are cumulus cells?

sub population of grannular cells around oocyte, eventually degenerate

what is a cumulus-oocyte complex (COC)?

oocyte + 2-3 cummulus layers + hyaluraunic acid

Corpus luteum

• luteinized granulosa + theca cells + capillaries

• yellow body (lots of lipid droplets for steroid production)

• a temporary collection of cells that forms on your ovary each menstrual cycle if you're still getting a menstrual period.

• appears right after an egg leaves your ovary (ovulation).

• job is to make your uterus a healthy place for a fetus to grow.

Unless a pregnancy intervenes, lifespan of CL is

~12 days

Hormone release during different phases of cycle

Proliferative phase: peak estrogen before peak of LH followed by peaking of FSH on edge of to secretory phase.

Secretory phase: Progesterone major peak, smaller estrogen increase

Proliferative phase

• resurfacing of epithelium

• cell proliferation in response to ovarian E

• development of spiral arteries & uterine glands

• cervical mucus becomes thin; forms channels that facilitate sperm passage

• follicular phase of ovary

Secretory/ovulation Phase

• thickening of whole layer due to cell growth & fluid retention

• As LH levels decline, CL begins to degenerate (~D24) → in absence of P secretion, uterine endometrium is shed & cycle begins again

When is endometrium maximally receptive to embryo implantation?

Day 21

Why is it called the secretory phase?

glands release glycogen rich secretion in case

What is the cervical plug?

thick and viscous prevent infection

If oocyte is fertilized

hCG is produced in increasing amounts beginning D9-13 after ovulation; hCG rescues the CL until placental progesterone can maintain the pregnancy

hCG

• Human chorionic gonadotropin

• in early embryo

• bind to LH, extend life of corpus luteum

Hormonal regulation of puberty

• initial hormonal events are the same in males & females

• in females, FSH stimulates E secretion by granulosa cells (LH stimuation provides T precursor from theca cells)

• cycles of proliferation & regression until sufficient growth occurs that withdrawal of steroid support (due to atresia of follicles) results in first menstruation (menarche)

• first ovulatory cycle often may not occur until a few months later

• concept of a critical weight to reach before menarche:

• specifically, a critical ratio of fat to lean – Why? (think about aromatase activity in adipose tissue as well as adipose-cell-derived leptin and GnRH release)

  • adipose tissue for nutrient reserve

  • adipose tissue has aromatase enzymes, increasing estrodial

Estradiol responsible for what during puberty?

• growth & maturation of breasts, reproductive organs

• fat redistribution

• bone maturation (growth → closure of epiphyseal plates)

• (all processes gradually completed over a ~4-year period)

What is menopause?

• cessation of menses for at least 12 months

• in North America, occurs at mean age of 51.4 years

• primary cause is depletion of ovarian follicles

Perimenopause

• extends from early 40s onward - « transitional years »

• ovarian function begins to wane - deprivation of estrogen (and its effects on FSH/LH secretion) can result in: hot flushes, insomnia, irritability, fatigue, headaches, depression/mood changes, loss of libido, poor mental performance/ nervousness, loss of skin elasticity

Menopause occurs at what age

median age of 51.4 years; can live 1/3 of life after ovaries have ceased functioning

Loss of ovarian E affects all tissues that have E receptors

• genital tissues: atrophy, vaginal dryness, higher incidence of vaginal infections (lose acid secretions)

• urinary tract: linings of bladder & urethra have E receptors; loss of E can lead to increased urinary frequency, urgency, even incontinence

• breasts: some atrophy

• CV system: atherosclerosis, stroke

  • estrogen has protective effects (decrease risk before menopause, with menopause causes increased level as men)

• skeleton: osteoporosis

Cumulus layer

also known as the cumulus oophorus, refers to a layer of cells surrounding the oocyte (egg cell) in the ovary