ANA HISTO FEMALE

Ovaries Almond-shaped bodies; 3cm long, 1.5cm wide, 1 cm thick; 2 layers covering ovaries:
germinal epithelium, outer layer of simple cuboidal epithelium, then tunica albuginea
dense CT inside the germinal epithelium

Cortex (outer) with a stroma of highly cellular connective tissue and ovarian follicles;
Medulla - loose CT and blood vessels entering through the hilum from mesenteries
suspending the ovary (no distinct border between cortex and medulla)

Early Development of the Ovary

First month Primordial cells migrate from yolk sac to gonadal primordia; divide and differentiate to
oogonia

Two month 600,000 oogonia - produce more than 7 million by 5th month

Third month Prophase of first meiotic division BUT ARREST after completing synapsis and
recombination.; primary oocytes - becomes surrounded by flattened support cells
(follicular cells) to form ovarian follicle

Seventh month Most oogonia have transformed into primary oocytes within follicles
However, many are lost through a slow, continuous degenerative process (atresia), which
continues through a woman’s reproductive life

Puberty Contains only 300,000 oocytes; reproductive life only 30-40 years; only about 450
oocytes are liberated, all others - atresia

Ovarian Follicles Consists of an oocyte surrounded by one or more layers of epithelial cells within a basal
lamina.

Fetal life - primordial follicles - consists of primary oocyte enveloped by a single layer of
the flattened follicular cells; follicles occur in the superficial ovarian cortex; spherical
about 25um; large nucleus containing chromosomes in the first meiotic prophase;
organelles concentrated near nucleus; basal lamina surrounds follicular cells - clear
boundary between follicle and vascularized stroma

Follicular Growth and Development

FSH Puberty; from pituitary, stimulated by GnRH from hypothalamus; small group of primordial
follicles ea mo. begins process of follicular growth

● Growth of oocyte (most rapid in first part of foll. Devt - 120um;

● Proliferation and changes in follicular cells;
● Proliferation and differentiation of the stromal fibroblasts around ea follicle
(growth of cell and nuclear enlargement; mitochondria numerous nad uniform;
RER extensive, Golgi move peripherally; formation of cortical granules
(specialized secretory granules) containing proteases - these lie inside the
plasma membrane and undergo exocytosis early in fertilization.

Early Primary Follicle Undergo mitosis; simple cuboidal epithelium around the oocyte; unilaminar primary
follicle

Late Primary Follicle Stratified follicular epithelium; granulosa; cells communicate through gap junctions;
multilaminar

Zona pellucida Between the first layer of granulosa cell, extracellular material accumulates here; 5-10um
thick; 4 glycoproteins

ZP3 and ZP4 (sperm receptors) binding specific proteins on sperm surface and inducing
acrosomal activation;
 Filopodia of granulosa cells and microvilli of the oocyte penetrate the zona pellucida,
allowing communication via gap junctions

Follicular theca Stromal cells immediately outside each growing primary follicle differentiate to form
follicular theca

Theca interna - well vascularized endocrine tissue; steroid producing cells secreting
androstenedione.

Theca externa - w/ Fibroblasts and smooth muscles merges gradually with the
surrounding stroma

Secondary Antral Granulosa cell layers secrete follicular liquid; coalesce, space enlarges, larger cavity
Follicles (antrum); now called secondary/antral follicles

Follicular fluid contains: GAG hyaluronic acid, growth factors, plasminogen, fibrinogen,
anticoagulant heparan sulfate, steroids (progesterone, androstenedione and estrogens)
with binding proteins

Mature (Graafian) Granulosa cells around the oocyte form a small hillock (cumulus oophorus), which
Follicles protrudes in the antrum; granulosa cells that immediately surround the zona pellucida
make up the corona radiata and accompany the oocyte when it leaves the ovary at
ovulation

Single large antrum (Graafian follicle) rapidly accumulates more follicular fluid and
expands to 2cm diameter; mature follicle forms a bulge at the ovary surface (seen in Ux);
granulosa layer becomes thinner; 90 days from a primordial follicle

Follicular atresia Follicular cells and oocytes die and are disposed of by phagocytic cells

Apoptosis & detachment (granulosa);

Autolysis (oocytes);
Collapse (zona pellucida)

Dominant follicle reaches most developed stage of follicular growth and undergoes
ovulation; other - atresia

Ovulation and Hormonal regulation

Ovulation Hormone stimulated process, by which the oocyte is released from the ovary; hours
before ovulation, mature dominant follicle develops a whitish ischemic area, stigma,
tissue compaction blocked blood flow

Just before ovulation, oocyte completes first meiotic division (arrested at prophase
during fetal life), divided into two daughter cells w equal chromosomes: one retains all
cytoplasm (secondary oocyte), other becomes (first polar body) - small nonviable cell
containing nucleus and minimal cytoplasm; after expulsion of first polar body, nucleus of
the secondary oocyte begins second meiotic division BUT arrests at metaphase AND
NEVER COMPLETES, unless fertilization occurs.

Hormonal Regulation of from pituitary, stimulated by GnRH from hypothalamus (↑estrogen = stimulate rapid
Ovulation pulsatile release of GnRH; ↑GnRH = surge of LH release from pituitary, triggers:

● Meiosis 1 is completed by the primary oocyte (yielding secondary oocyte & first
polar body)
● Granulosa cells ↑ produce - prostaglandin and EC hyaluronan
● Ballooning at the stigma - ovarian wall weakens as activated plasminogen
(plasmin) from broken capillaries degrades collagen in the tunica albuginea and
surface epithelium
● Smooth muscle contractions begin in the theca externa triggered by

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 prostaglandins diffusing from follicular fluid

↑pressure - weakens wall - rupture of ovarian surface at the stigma;

Oocyte + corona radiata w/ follicular fluid - expelled by SM contractions;
Ovulated 2ndary oocyte - adheres loosely to ovary surface in FF and is drawn into the
opening of the uterine tube where fertilization may occur;
NOT Fertilized within 24 hrs, secondary oocyte begins to degenerate;
Cells of ovulated follicle that remain the ovary differentiate (influence of LH) and give rise
to corpus luteum

Corpus Luteum After ovulation, granulosa cells and theca interna of the ovulated follicle reorganize to
form a large temporary endocrine gland (corpus luteum) in the ovarian cortex → to
produce progesterone (in addition to estrogen);
Ovulation →collapse and folding of the granulosa and theca layers, and blood from
disrupted capillaries accumulates as a clot in the former antrum;
Granulosa is now invaded the capillaries; increase in size (20-35um) without dividing,
takes up 80% of the corpus luteum (granulosa lutein cells) - have lost many features of
protein-secreting cells + role as aromatase conversion (androstenedione → estradiol)

CL of Menstruation LH surge → CL secrete progesterone (10-12 days);

w/o further LH & w/o pregnancy, CL cease steroid production, undergo apoptosis;
After degeneration, blood progesterone ↓ & FSH secretion ↑ again → growth of another
group of follicles;
CL persists for part of only 1 menstrual cycle (CL of menstruation);
Remnants → phagocytosed by macrophages, after wc fibroblasts invade the area and
produce a dense CT called corpus albicans

CL of Pregnancy CL depends on pregnancy; ovulatory LH surgeon cause CL to secrete prog. (10-12

days); To prevent drop in blood progesterone, trophoblast cells of the implanted embryo
produce HCG (similar to LH); HCG - promotes further growth of CL, stim progesterone (to
maintain uterine mucosa); CL of pregnancy becomes very large, maintained by HCG for
4-5 months → placenta (produces progesterone & estrogen - to maintain uterine
mucosa) ; degenerates and is replaced by large corpus albicans

UTERINE TUBES Oviducts; 10-12cm length; (see Gross Female Notes for parts);
HISTOLOGY:
Folded mucosa; thick muscularis with circular and longitudinal SM; thin serosa covered by
visceral peritoneum with mesothelium; numerous branching, longitudinal folds of mucosa
- most prominent in ampulla (cross section resembles a labyrinth); mucosal folds
become smaller int region closer to uterus, absent in intramural part.

MUCOSA:
Simple columnar epithelium on LP of smooth CT; two impt cell types:
● Ciliated cells sweep fluid toward uterus;
● Secretory or peg cells - nonciliated, darker staining, apical bulge to lumen,
secrete nutritive mucus

UTERUS (see Gross Female Notes for parts);

HISTOLOGY:
Perimetrium - outer CT layer; continuous with ligaments (adventitial in some), largely
serosa covered by mesothelium;
Myometrium - thick tunic of highly vascularized bundles of SM, parallel to long axis;
during pregnancy - hyperplasia, hypertrophy, and increased collagen production
Endometrium - mucosa - simple columnar epithelium, tubular uterine glands (full
thickness); non bundled type 3 collagen fibers;
2 layers of Endometrium:
● Basal layer - adjacent to myometrium; highly cellular LP; deep basal ends of
uterine glands; remains unchanged
● Superficial functional layer - spongier LP; richer in ground substance;
profound changes during menstrual cycle

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 Arcuate arteries in the middle of the myometrium send two sets of smaller arteries into
the endometrium: straight → basal layer; long spiral (progesterone sensitive) → blood
throughout functional layer; branch with numerous arterioles supplying a rich, capillary
bed that includes many dilated, thin-walled vascular lacunae drained by venules

Menstrual cycle Menstrual period (3-4 days); Proliferative (8-10 days); Secretory - begins at ovulation and
lasts 14 days

Proliferative phase Follicular; estrogenic; mucosa 0.5mm; Estrogen → endometrium → regeneration of

functional layer; simple columnar epithelium, straight tubules with narrow nearly empty
lumen; spiral arteries lengthen as functional layer is re-established; at end (2-3mm thick)

Secretory Luteal; progesterone → glycogen → dilate glandular lumen & causing glands to become
coiled → thin-walled blood-filled lacunae; 5mm;
If w/ fertilization, day after ovulation, embryo transported to uterus 5 days later;
progesterone inhibits uterine contraction

Menstrual Implantation does not occur, CL regresses and blood progesterone ↓ 8-10 days after
ovulation; spasms in the spiral arteries of functional layer & ↑synthesis of
prostaglandins

Embryonic implantation, decidua and the placenta

Zygotes undergoes mitotic cleavages (blastomeres) in a compact aggregate (morula);

NO growth occurs (same size); 5 days after fertilization embryo reaches uterine cavity,
blastomeres have moved to form a central cavity in the morula → blastocyst stage;
Blastomeres go to peripheral layer (trophoblast) around the cavity; few cells inside the
layer make up the embryoblast or inner cell mass; blastocysts remain in the lumen of
the uterus for about 2 days;

Implantation (lasts 3 days) → embryoblast rearrange into two cavities → amnion and
yolk sac → two cavities contact (bilaminar embryonic disc) develops with epiblast
(amnion) & hypoblast (yolk sac) EA; HY

Cytotrophoblast Layer of mitotically active cells immediately around the amnion and yolk sac; synthesize
anti inflammatory cytokines;

Syncytiotrophoblast More superficial, non mitotic mass of multinucleated cytoplasm; stroma

9th day after ovulation, embryo totally implanted

Stroma Fibroblasts become enlarged, polygonal, more active in protein synthesis, and are now
called decidual cells; endometrium is now decidua:

Basalis bet. Implanted embryo & myometrium;

Capsularis bet embryo & uterine lumen;
Parietalis side of uterus, away from embryo

Placenta Chorion - embryonic part; derived from trophoblast and basalis (maternal);
Exchange chorionic villi (embryo) and lacunae of basalis (maternal blood)

Primary villi Appear 2 days after implantation

Secondary villi Form on the 15th day; primary villi are invaded by extraembryonic membrane

Tertiary villi Few more days; 2ndary villi differentiates to form capillary loops

CERVIX

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 Histologically different from uterus; deeper wall part of cervix is made up of dense CT,
with much less SM than rest of uterus; relatively rigid during pregnancy and helps retain
fetus in uterus

Endocervical mucosa Simple columnar epithelium; cervical glands (mucus); lacks spiral arteries, do not change
2-3mm thickness, not shed

Exocervical mucosa Nonkeratinized stratified squamous epithelium; continuous with vagina

Transformation zone Junction; intraepithelial neoplasia; Cervical cancer; epithelial dysplasia - mean age of 54

VAGINA

Muscular layer - circular (near mucosa); thick longitudinal (near adventitia); dense CT of
adventitia (rich in elastic fibers);

Mucosa - stratified squamous non-keratinizing (150-200 um);

Stimulated by estrogen, epithelial cells secrete glycogen, low pH in vagina; LP rich in
elastic fibers, numerous papillae; with lymphocytes and neutrophils; greater vestibular
glands (Bartholin) - mucus

External genitalia Vulva; stratified squamous epithelium

Vestibule Wall includes tubuloacinar vestibular glands

Labia minora Lacking hair follicles with numerous sebaceous glands

Labia majora Homologous and similar to scrotum

clitoris Erectile structure; homologous to penis with paired corpora

cavernosa

Legend:
FF- follicular fluid
SM - smooth muscle