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Histology of the female reproductive system

Taken from Mescher, Junqueira’s Basic Histology: Text and Atlas, Twelfth Edition
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Oocyte grow rapidly under stimulation by FSH
o Nucleus enlarges, numerous mitochondria, extensive ER, increased
Golgi
Follicular cells divide forming a simple cuboidal epithelium surrounding the
oocyte
o Unilaminar primary follicle
Follicular cells continue to proliferate to produce a stratified epithelium –
granulosa; cells communicate via gap junctions
o Multi-layered primary follicle
A layer of extracellular material (zona pellucida) develops between the
oocyte and granulosa cells; comprises 4 glycoproteins secreted by the
oocyte (ZP1-4)
Fillopodia of follicular cells and microvilli of the oocyte penetrate the zona
pellucida – communication via gap junctions
As the follicles grow, they move deeper into the ovarian cortex
o Spaces develop within the granulosa cells as the cells secrete follicular
fluid; this accumulates and the spaces coalesce to form the antrum
o Follicular fluid contains growth factors and other substances, including
steroids with binding proteins
o Follicles are now secondary/antral follicles
Granulosa layer is reorganised
o Hillock of cells is formed (cumulus oophorous; surrounds oocyte and
projects into the antrum
o Granulosa cells in the vicinity of the oocyte and linked make up the
corona radiate, which accompany oocyte upon ovulation
As the follicle develops, the stroma nearby differentiate to form the follicular
theca; differentiates into

Theca interna: well-vascularised endocrine tissue; differentiate as
steroid-producing cells
o Theca externa: fibrous outer coating with smooth muscle and
fibroblasts
Theca internal cells secrete androstenedione – transports to granulosa
o Under influence of FSH, granulosa cells synthesise aromatase, which
converts androstenedione to oestradiol
o Oestradiol enters capillaries for distribution around the body
Boundary between stroma and theca externa not clear, nor is that between
theca externa and interna; boundary between theca interna and granulosa
well-defined by thick basement membrane
Dominant follicle reaches most developed stage and is ovulated; known as
mature/preovulatory/Graafian follicle
Antrum increases in size and oocyte adheres to follicle wall via cumulus
oophorous of granulosa cells
Granulosa cell layer becomes thinner, due to reduced proliferation relative to
size increase of the antrum; thick thecal layer
Takes ~90 days from primordial to mature follicle
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Taken from Mescher, Junqueira’s Basic Histology: Text and Atlas, Twelfth Edition
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Follicular atresia
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Most ovarian follicles undergo degenerative process of atresia
Apoptosis of follicular and oocyte cells followed by phagocytosis
Follicles at any stage pre-maturity may become atretic
Process
o Apoptosis and detachment of granulosa cells
o Autolysis of oocyte
o Collapse of zona pellucida
Macrophages invade the follicle and phagocytose debris
Fibroblasts occupy and produce a collagen scar
Takes place from before birth to just after menopause, but most prominent
just after birth (decline of maternal hormones) and during puberty and
pregnancy

Ovulation
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Large mature primary oocyte leaves ovary and captured by fimbriae of the
uterine tube
Usually one oocyte expelled, but could be none or one
Before ovulation, the mature follicle bulging against the tunica albuginea
develops an ischemic area (stigma; compaction of tissue blocks blood flow)
Granulosa cells and theca interna begin to secrete progesterone and
oestrogen
Rapid rise in oestrogen from the dominant follicle causes LH surge, stimulating
ovulation
LH stimulates the preovulatory follicle to synthesis prostaglandins, hyaluronate
and fluid production
Progesterone, FSH and LH stimulate several enzymes, including plasmin and
collagenases, on and around the follicle
o Weakens granulosa layer, cumulus oophorous and tunica albuginea
Increased pressure of follicular fluid and wakening of granulosa layer results in
ballooning and rupture of the stigma
Prostaglandins in the follicular fluid stimulates contraction of the theca
externa smooth muscle
Oocyte and corona radiate plus follicular cells and those from the cumulus
are expelled
Oocyte completes first meiotic division just prior to ovulation; equal
chromosomal segregation but unequal segregation of cytoplasm, leading to
a polar body (nonviable)
Oocyte begins meiosis II, arresting in metaphase
Ovulated secondary oocyte loosely adheres to the ovary surface due to
hyaluronate rich, coagulating follicular fluid
Drawn into uterine tubes; if not fertilised, will degrade after 24 hours

Corpus luteum
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Granulosa cells and theca interna reorganise to form the corpus luteum in the
ovarian cortex
After ovulation, the granulosa cells and thecal layers collapse and fold, blood
from disrupted capillaries forms a clot where the antrum was
Granulosa is invaded by capillaries
LH causes histological and functional changes in both cell types for
progesterone and oestrogen synthesis
o Hypertrophy of granulosa cells (lutein cells) – convert androstenedione
to oestrogen
o Theca cells become smaller lutein cells – progesterone and
androstenedione
Fate of corpus luteum dependent on whether a pregnancy occurs or not;
secretes progesterone for 10-12 days following the LH surge

No pregnancy
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In absence of pregnancy, cells stop synthesising steroids and apoptose
Reduced progesterone synthesis results in menstruation
After degeneration of the corpus luteum, oestrogen levels drop, releasing FSH
from inhibition
More follicles stimulated to grow in another cycle
Remnants of the corpus luteum phagocytosed by macrophages; fibroblasts
then invade and produce a scar of connective tissue (corpus albicans)

Pregnancy
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Trophoblast cells of the implanting embryo secrete human chorionic
gonadotrophin (hCG), which acts similarly to LH
HCG targets the corpus luteum; maintains it to maintain progesterone
synthesis and thus the uterine mucosa
Progesterone also stimulates the uterine mucosal glands, for nutrition of the
embryo before placenta is in place
Corpus luteum of pregnancy hypertrophies and is maintained by HCG for 4-5
months
o Placenta then produces progesterone and oestrogens at sufficient
levels
Corpus luteum degenerates and replaced by a corpus albicans

Uterine tubes
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Muscular tubes with considerable mobility
Regions
o Funnel shaped infundibulum with fimbriae
o Ampulla, long expanded area where fertilisation occurs
o Isthmus, narrow region near uterus
o Uterine/intramural part, passes through wall of the uterus
Wall of oviduct is folded mucosa, thick muscularis (with interwoven
longitudinal and circular muscle) and peritoneum with mesothelium
Clinical note

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Salpingitis is inflammation of the uterine tubes
Salpingectomy is surgical removal of the uterine tubes

Mucosa has branching, longitudinal folds, particularly in the ampulla, not
present in the intramural segment
Mucosa is simple columnar epithelium on a lamina propria of loose
connective tissue
Two cell types, ciliated cells and secretory peg cells (apical side bulges into
lumen)

Cilia beat toward the uterus, moving along a viscous fluid film produced by
peg cells, which contains glycoproteins and nutrients
Both cell types hypertrophy and cilia elongate in response to oestrogen
during the follicular phase, and atrophy in the luteal phase
At the time of ovulation, the uterine tubule shows active movement
o Infundibulum moves closer to ovary and partially covers its surface
o Muscle contractions of the fimbriae and ciliary activity move the
oocyte along the uterine tubes to the ampulla
The secretions from peg cells has nutrient and protective functions for the
oocyte and sperm, including factors promoting capacitation
Oocyte viable for 24 hours
Following fertilisation, the oocyte finishes its second meiotic division to form
the ovum
Diploid cell from fertilisation is the zygote
Contraction of the oviduct and ciliary movement transport the zygote to the
uterus; ciliary activity not essential

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Clinical note
Proinflammatory scar tissue can block uterine tubes, preventing the
embryo from reaching the uterus
May implant in the uterine tube wall – ectopic pregnancy
The lamina propria may react like the uterine endometrium and form
decidual cells
Due to small diameter and inability to expand, tubes cannot contain the
growing embryo and will rupture – haemorrhage, which can be fatal

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Uterus
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Pear shaped, thick muscular walls
Uterine tubes enter into the body; curved, superior area is the fundus
Uterus narrows in the isthmus to become the cervix; lumen is the internal os,
entering into the cervical canal
Three major layers
o Perimetrium: outer connective tissue layer, continuous with ligaments
o Myometrium: thick smooth muscle, highly vascularised
o Endometrium: mucosa of simple columnar epithelium
Thickness and structure of the endometrium influenced by ovarian hormones

Myometrium
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Bundles of smooth muscle plus connective tissue with blood vessels
Mixture of longitudinal and circular muscle

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During pregnancy, there is hyperplasia and hypertrophy of the endometrium,
with secretion of collagen to increase strength of the connective tissue
After pregnancy, there is cellular apoptosis and degradation of collagen to
shrink the uterus back to normal size

Endometrium
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Simple columnar epithelium with both ciliated and secretory cells
Secretory cells form lining of the uterine glands, penetrating the full thickness
of the endothelium
Two zones
o Basal layer adjacent to the myometrium contains highly cellular lamina
propria with lots of fibroblasts, and basal ends of the uterine glands
o Superficial functional layer has more spongy and less cellular lamina
propria, length of the gland and surface epithelium
Functional layer changes during menstruation while the lower layer does not
Arcuate arteries in the middle layers of the myometrium send arteries into the
endometrium
o Straight arteries supply the basal layer only
o Long, progesterone sensitive spiral arteries extending and subdividing
to vascular lacunae, supplying the functional layer

Taken from Mescher, Junqueira’s Basic Histology: Text and Atlas, Twelfth Edition
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Taken from Mescher, Junqueira’s Basic Histology: Text and Atlas, Twelfth Edition
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Placenta
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Placenta is the site of nutrient, waste, O2 and CO2 exchanges between
mother and foetus, and comprises tissues from both
Embryonic part of the placenta is the chorion, derived from trophoblast
Maternal part is from the decidua basalis
Two trophoblast layers form the chorionic villi, project into the blood-filled
lacunae to provide larger surface area for exchange
Villi are invaded by embryonic mesenchyme
By the end of the third week, wide capillaries continuous with the embryonic
vasculature develop in the villi
Placenta is also an endocrine organ, producing human chorionic
gonadotrophin (hCG), oestrogen, progesterone and other hormones

Clinical note
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Initial attachment usually occurs on ventral or dorsal walls of
the body of the uterus
Sometimes the embryo attaches close to the internal os
Placenta will be located between the foetus and the
vagina, obstructing passage of the foetus at parturition
Known as placenta previa, will need caesarean delivery

Uterine cervix
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Lower, more cylindrical part of the uterus
Different histology from the rest of the cervix
Endocervix has mucous secreting simple columnar epithelium on a thick
lamina propria
External os is covered by exocervix mucosa, which is stratified squamous
epithelium
Transformation zone is where simple columnar epithelium undergoes an
abrupt transition to stratified squamous
Deep middle layer of the cervix has little smooth muscle consisting mainly of
connective tissue
Lymphocytes and leukocytes from the stroma penetrate the epithelium,
providing local immune defence
Intense collagenic activity before parturition allows softening and dilation of
the cervix for passage of the foetus
Endocervical mucosa contains many branched cervical glands which
produce mucous
Hormonal shifts cause swelling of the mucosa, but not to the same extent as
the uterus body, and it is not desquamated during menses
However, there are changes in the mucous secretion; at ovulation, ample
amounts of watery mucous are secreted, which facilitate sperm movement

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Progesterone in the luteal phase causes viscous mucous, preventing sperm
traversing into the uterus
During pregnancy, the cervical glands proliferate and secrete a lot of viscous
mucous to form a plug in the endocervical canal

Taken from Mescher, Junqueira’s Basic Histology: Text and Atlas, Twelfth Edition
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Pregnancy and lactation
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Several hormones contribute to growth of the mammary glands during
pregnancy (oestrogen, progesterone, prolactin, human placental lactogen)
Alveoli proliferate (composed of cuboidal epithelium, with myoepithelial cells)
and ducts proliferate
Stroma becomes less prominent; intra-lobular loose connective tissue is
infiltrated by lymphocytes and plasma cells (become more numerous toward
end of pregnancy for IgA secretion)
Late in pregnancy the alveoli and ducts dilate due to an accumulation of
colostrum (rich in proteins, vit A, and electrolytes) which is produced under
influence of prolactin; antibodies added
Following parturition, levels of oestrogen and progesterone declines, and
glandular alveoli become active in milk production
Merocrine secretion of protein, apocrine secretion of lipids, plus other
components (sugar, lactose etc
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Clinical note
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Nursing action of child on nipple when breastfeeding stimulates
tactile receptors
Results in oxytocin release from the posterior pituitary
Oxytocin causes contraction of the smooth muscle of the
lactiferous sinuses and ducts and myoepithelium of the alveoli
Results in the milk-ejection reflex
Negative emotional stimuli, such as frustration, anxiety, or anger,
can inhibit oxytocin release, preventing milk ejection

Postlactional regression
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When breast feeding is stopped (weaning), most alveoli that developed
secretory ability degenerate; apoptosis and sloughing of cells
Dead cells and debris removed by macrophages, and autophagy by other
epithelial cells
Duct system returns to pre-pregnancy morphology
After menopause, alveoli and ducts reduce further in size, and reduced
fibroblasts, collagen and elastic in the stroma, with increased adipose

Clinical note
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Most incidences of breast cancer (mammary carcinoma) arise
from epithelial cells of the lactiferous ducts
Metastasis via blood or lymph are often responsible for mortality
Axillary lymph nodes are removed surgically and examined
histologically for metastasised cells
Early detection from self-examination, mammography, ultrasound,
etc
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Mescher
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Twelfth Edition

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