William A Beresford MA, D Phil ©
Professor of Anatomy
Anatomy Department, West Virginia University, Morgantown, USA
This is a tubular system for the production of ova, and the reception of
spermatozoa, their transport and union. It accommodates the fertilized
oocyte and ensuing fetus, then expels the fetus at term. The ovary and placenta
also have hormone-secreting functions, for instance, to prepare the uterine
mucosa to receive, accept, and sustain the fertilized oocyte. Mammae are
modifications of the skin for feeding the infant. Powerpoint
l General structure
l Covered by mostly simple epithelium (variably columnar, cuboidal, or
2 under which is a loose CT, a nominal capsule - tunica albuginea.
3 Has a stroma of atypical fibroblasts; collagen, as reticular fibres,
is present, but not a dominant element; and stromal cells secrete hormones.
4 A fold of peritoneum, the mesovarium, connects the ovary at its
hilum to the broad ligament, and sends many blood vessels to the fibrous,
central, medullary, region of the ovary.
5 Peripheral, cortical, regions have many primordial and
primary follicles, maturing Graafian follicles, which shed the ova
(to be fertilized in the upper third of the Fallopian tube), and glandular
6 Certain vestigial structures remain after development has ceased.
These take the form of blind epithelium-lined tubules - epoöphoron and
paroöphoron - lying in the broad ligament by the ovary.
7 Hilar stromal cells may include hormone-secreting hilus cells,
resembling testicular Leydig cells, which occasionally give rise to tumours
causing a hyperandrogenic syndrome in the woman.
2 Ovarian events and structures Fig. 11
Primordial follicle with primordial germ calls migrated from the yolk
| . sac
Primary follicle of . At any time during development
oocyte surrounded by ........ a follicle can degenerate, and
follicular cells . most do, becoming an
| . |
| . |
develops under stimulus of . Atresic follicle
FSH of anterior pituitary . |
| . |
Graafian follicle . |
large, fluid-filled, cyst-like . followed by invasion by
| . vessels and CT; if a theca
| . interna was present, it
grows, extends to the surface of forms a temporary glandular
ovary, and bursts at mid-cycle tissue - the
/ | |
/ | Interstitial gland
shedding ovum Empty cavity collapses more obvious in rodents
to be caught Surrounding cells grow than woman; other names are
by the nearby large and glandular, corpus atreticum &
/ forming, under the influence pseudolutein body
/ of pituitary LH, a
Fallopian tube |
grows considerably grows for 12 days
under the influence of only, if the oocyte
placental hCG, if the is not fertilised
oocyte is fertilised |
Corpus luteum Corpus luteum
of pregnancy of menstruation
Glandular cells degenerate, and
fibroblasts form a pale scar-like
formed while the cycle starts again
3 Hormonal background
l Dealing with changing structures, either developing or degenerating; with
marked changes in events and appearances at the menarche, when ovarian
cycles begin, and the menopause, when they end.
2 The constant physiological change makes difficult recognizing pathological
changes, e.g., uterine bleeding. Female reproduction is a considerable burden
in its energy demands, e.g., for fat storage and lactation, which can only
be met on an intermittent, i.e., cyclic, basis.
2 FSH and LH/ICSH are pituitary gonadotrophins - hormones with the
gonads as their target organ.
3 Corpus luteum is also influenced by hormones produced by the placenta,
if fertilization has occurred - chorionic gonadotrophins.
4 Distinguish between hormones acting on the gonads, and those produced
by the gonads and acting on other organs, e.g., uterus.
4 Ovarian/menstrual cycle (with details not included in Fig. 11)
l Maturation of oöcyte
- (a) Oocyte increases in size.
- (b) Golgi complex and other organelles become more dispersed in the
cytoplasm, and lipid droplets appear.
- (c) Zona pellucida of glycoprotein forms between the oocyte and
surrounding follicular cells; both extend processes into it. The
zona pellucida may protect the ovulated and fertilized oocyte from
phagocytosis and immune rejection.
2 Development of follicular/granulosa cells and follicle
(A caution for the primary-secondary-tertiary staging of follicles: ask
in your own setting how these terms and 'Graafian' are to be applied.)
- (a) Follicular cells are present as a single squamous layer, encircling
the dormant oocyte (stage of primordial follicle).
- (b) The primary follicle arises by enlargement of the follicular cells
- they become cuboidal - and of the oocyte.
- (c) Follicular cells proliferate to a multilayered state (secondary/
- (d) Primary oocyte moves to an eccentric position. Fluid forms,
separating follicular cells and collecting in antra (spaces). Further
cell multiplication, and fluid coalescence, lead to a large follicle, with
liquor folliculi filling a single antrum (antral/vesicular/
- (e) In the follicular lining of granulosa cells, a hillock -
cumulus oöphorus - encloses the oocyte.
- (f) The granulosa cells synthesize materials for the oocyte, and also
oestrogens, and inhibin to reduce FSH release from the pituitary.
3 Changes in stroma around maturing follicle
- (a) Stromal fibroblast cells build a capsular theca, which
- (b) differentiates into:
.. (i) an inner theca interna: ovoid secretory cells, with lipid droplets; vascular;
.. (ii) an outer theca externa: fusiform fibroblastic cells packed densely.
- (c) The growing theca interna secretes androgenic precursors of
oestradiol-l7b for aromatase-mediated conversion by the granulosa cells.
- (d) A glassy basal lamina develops between the theca cells and the
membrana granulosa lining the follicle.
- (a) A sudden surge in LH, coupled with an increase in FSH and a peaking
oestrogen level, triggers ovulation, after the completion of meiosis I by the
- (b) Graafian/antral follicle, grown huge (l5 mm diameter), extends
to and protrudes from the ovarian surface.
- (c) Protruding apical tissue weakens at the stigma, by apoptosis, and
enzymatic action on its matrix, and ruptures, helped by thecal cellular
contractions; the fluid flows out.
- (d) The fluid takes with it the already floating secondary oocyte (a
first maturation division having recently occurred), and some attached
granulosa cells as a corona radiata.
5 Corpus luteum: formation, function and fate
6 Signs of follicular atresia (aborted development)
- (a) Burst follicle's wall collapses, becoming folded/plicated.
- (b) Lining granulosa cells become secretory granulosa lutein cells
- the main component of the corpus luteum of menstruation (CLM), or of
theca interna cells become secretory theca lutein cells (found as
small nests of darker cells at the periphery of the main mass of granulosa
lutein cells, and accompanying vascular septa into the CLM).
- (c) Lutein cells become enlarged, with many lipid droplets (vacuoles,
in H&E preparation) and much smooth ER, and secrete the steroid hormone -
- (d) which is collected in capillaries that grow in from the theca interna.
- (e) Progesterone makes the uterine mucosa secretory; and inhibits
menstruation and uterine muscle contraction, if implantation occurs.
- (f) The centre of the collapsed follicle fills with clotted blood, which
is reorganized by ingrowing fibroblasts and capillaries to form a pale,
central core of CT.
- (g) Late in pregnancy, or late in the menstrual cycle (if the shed oocyte
is not fertilized), the glandular lutein cells degenerate; the corpus luteum
shrinks, and is replaced by a small pale mass of hyalinized CT - corpus
albicans (white to the naked eye in the fresh, unstained ovary).
.. (a) Granulosa lining breaks up and sheds apoptotic cells into the antrum.
.. (b) Follicle's wall collapses; vessels and CT cells invade.
.. (c) Basal lamina thickens to become a 'glassy membrane'.
.. (d) Oocyte's nucleus shrinks and becomes pyknotic.
.. (e) Zona pellucida folds in, as the oocyte degenerates.
.. (f) Theca interna cells enlarge, becoming more glandular to form a temporary interstitial gland.
B FALLOPIAN/UTERINE TUBE (oviduct)
l Four parts: (a) infundibulum with the fimbria - a fringe of
processes, engorgeable with blood and moved by smooth muscle to catch the oocyte,
(b) wide ampulla, with a cell-ensnaring labyrinth of protruding mucosal
processes, (c) narrow isthmus down to the uterus, and (d) an intramural/
interstitial section through the uterine wall.
2 Lined by a highly folded mucosa, comprising a cellular lamina propria
covered by a simple columnar epithelium of
3 columnar ciliated cells, and secretory cells, varying in
height and secretory activity during the menstrual cycle. Secretion
is more in the late oestrogen phase around ovulation than in the post-ovulatory
progesterone phase. Cilia beat toward the uterus.
4 Muscularis of inner, circular, smooth muscle, and a few outer,
5 Covered outside by a serosa, with nerves and blood vessels.
6 Functions - meeting place for sperm and oocyte; helps 'capacitation'
of sperm to their most energetic and zona pellucida-penetrating state; nourishes
and transports the zygote.
l Outer serous coat (perimetrium), with vessels, nerves, and
2 Myometrium of interwoven smooth muscle, capable of a great
hypertrophy during pregnancy, with many blood vessels in the middle stratum
3 Mucosa/endometrium with:
l simple, columnar, epithelial lining (some cells ciliated);
2 simple, tubular mucous glands;
3 loose vascular stroma of special fibroblasts, reticular fibres and
much ground substance; some stromal cells can become decidual
around the implantation site;
4 helicine/coiled spiral arteries, a capillary bed, and veins.
4 Mucosa of the sexually mature woman experiences cyclic menstrual
changes, involving all elements and considerable changes in mucosal thickness,
and driven hormonally by the ovary:
l Oestrogens, e.g., oestradiol, from the growing follicle cause cell
proliferation, and an increase in endometrial height.
2 Progesterone, formed by the corpus luteum, then increases cell
secretion and glycogen accumulation, and the stroma dilates with
fluid. The glands coil and sacculate. Spiral arteries continue to
grow up towards the surface.
3 Helicine arteries rhythmically constrict, then dilate, inducing
menstruation or breakdown of the endometrium, altered in the last few days of
the secretory phase by a reduction in progesterone level, and by cytokine
signals for cellular apoptosis. This sloughing of the functional layer
of the endometrium is unaccompanied by blood clotting.
4 Regeneration (physiological) takes place from the basal layer
of the endometrium, where the epithelium survives at the bottom of the glands.
5 The mucosa may experience these cyclic changes minimally, even though no
oocyte was shed from the Graafian follicle - an anovulatory cycle.
5 Uterine cervix differs from the corpus thus:
- It has more collagen and elastic in the wall than muscle.
- Mucosa is furrowed by complex clefts - plicae palmatae; and does
not participate in menstruation.
- Lining columnar epithelial cells produce a mucus, richly hydrated and
penetrable at mid-cycle.
- Epithelium changes to stratified squamous on the portio vaginalis.
The boundary between simple columnar and stratified squamous epithelia is
unstable, and shifts position by a process of columnar-to-squamous conversion.
This transformation zone is prone to dysplasia, then malignant change, which can be
detected early by examining 'Pap' smears.
l Adventitia of CT, with abundant nerves and blood vessels, merges with
some longitudinal and a few circular smooth muscle bundles, around a
wide collagenous lamina propria. All these layers loosen in gestation.
2 Epithelium is stratified squamous, rich in glycogen (to promote
the growth of benign lactobacilli in the lumen), and influenced by gonadal
hormones, but not to the degree seen in rodents.
3 Mucosa has transverse folds or rugae, and may have lymphoid nodules,
but is without glands.
E EXTERNAL GENITALIA/VULVA
l Labia majora and minora, vestibule and hymen - skin,
or stratified squamous epithelium on a loose, fatty or vascular lamina propria.
2 Clitoris and vestibular bulbs - erectile tissue.
3 Sensory receptors are distributed widely in the clitoris, vestibule
4 Bartholin's glands - mucus-secreting, compound, tubulo-alveolar -
are homologues of the male Cowper's glands. Other, minor, vestibular, mucous
glands lie near the urethra and clitoris.
F MAMMARY GLAND/BREAST/MAMMA
l A collection of compound, tubular (tubulo-alveolar, when active)
glands grouped around the
2 nipple, where the lactiferous duct of each gland opens.
3 Glands are in lobes, separated by dense interlobar CT.
4 In each lobe are:
5 Lactiferous ducts are lined successively by cuboidal, columnar,
stratifed columnar, and stratified squamous epithelia. Each duct widens below
the nipple into a sinus.
- (a) a stroma of CT - loose collagenous and adipose tissue, with many
lymph and blood vessels;
- (b) parenchymal tissue of alveoli and ducts, lined with secretory,
cuboidal and columnar epithelia. Alveoli and ducts also have
myoepithelial cells between epithelium and basal lamina.
l Cornified stratified squamous epithelium covers a stroma of elastic
fibres, smooth muscle, and collagen, through which pass the lactiferous
2 Epithelium is continuous with the somewhat pigmented, glabrous (hairless)
epidermis of the surrounded areola, with its sebaceous glands and
high dermal papillae.
3 The many autonomic nerve fibres to the nipple's smooth muscle
control its rigidity for suckling, and the relaxation of the milk sinuses.
4 Numerous sensory receptors and nerve fibres are present.
l Prepubertal period
.. (a) Nipple remains small and weakly pigmented.
.. (b) Glands stay rudimentary as multiple, branched, tubular units in a CT stroma.
.. (a) Oestrogen promotes ductal growth, and the formation of stromal
.. (b) Increasing levels of progesterone cause some alveoli to bud out
from the duct ends.
3 Early pregnancy
Progesterone and oestrogen cause a marked epithelial proliferation, with
increased branching of ducts, which bud out and form many alveoli; these form
at the expense of stromal tissue.
4 Late pregnancy and post-parturition
- (a) Prolactin/mammotrophic hormone of the anterior pituitary and
placenta promotes an 'apocrine' secretory activity in alveolar cells;
first of protein-rich colostrum, then milk.
- (b) Milk comprises:
.. (i) proteins, e.g., casein (seen as granules in EM);
.. (ii) lactose;
.. (iii) minerals;
.. (iv) fat (seen as osmiophilic droplets in EM) extruded apically as large, membrane-bound bodies;
.. (v) water.
- (c) Secretion needs adequate nutrition, and proper levels of thyroid,
adrenal, and other hormones.
(a) Numerous white blood cells infiltrate the stroma; some of which
(b) on gaining access to alveolar lumens, phagocytose the secretion
and become colostrum bodies, seen in the first few days after
(c) The actual release of milk depends on the stimulus of suckling, acting on
receptors in the nipple, which inform the brain to liberate pitocin
(let-down hormone) from the pituitary's posterior lobe. This hormone makes the
myoepithelial cells of ducts and alveoli contract.
6 Post-lactational regression and post-menopausal involution
- (a) If the milk is not suckled, it accumulates and secretion slows down.
- (b) Alveolar cells die by apoptosis. The secretions and degenerating
alveolar cells are resorbed, leaving the gland with ducts, but fewer alveoli.
- (c) After the menopause or surgical oophorectomy, the alveoli and ducts
regress further, cysts may form, and the CT tends to become pale, acellular
The placenta, with the umbilical cord and uterine mucosa, provides for the
physiological exchange of oxygen, nutrients, and waste materials between
the fetal and maternal circulations across the placental barrier, which
protects the fetus from some infections. The placenta also performs
metabolic transformations and synthesizes chorionic hormones:
gonadotrophin, prolactin, oestrogen, progesterone, etc.
l Fertilization and blastocyst formation Images - Visembryo
l Oocyte, when penetrated by a spermatozoon (by enzymatic action),
completes its second meiotic/maturation division, with the formation of
another polar body.
2 After one entry, the zona pellucida reacts, becoming impenetrable by other sperm.
3 The condensed sperm head turns itself into the male pronucleus, with reconstitution
of the nuclear membrane and lamina, and of the chromatin.
4 After DNA replication in male and female pronuclei, these fuse, and male
and female chromosomes pair up to give the diploid 46.
5 Over roughly four days, the zygote passes down the uterine tube, dividing to
form a solid mass of cells - the morula.
6 Fluid accumulates amongst the cells resulting in a blastocyst.
7 Blastocyst remains free in the uterine lumen for another two or so days.
8 Blastocyst has an:
.. (a) outer shell of trophoblastic cells;
.. (b) inner cell mass to become the embryo;
.. (c) outermost zona pellucida.
9 Blastocyst sloughs off the zona pellucida, and implants in the
glandular uterine mucosa.
10 Occasional ectopic sites of implantation are the Fallopian tube,
peritoneal cavity, and ovary.
l Trophoblastic cells, coming into contact with the uterine epithelium,
attach, proliferate, and invade into the stroma.
2 The blastocystic structure sinks in deeper to become covered by mucosa
(uterine mucosa is henceforth termed decidua).
Mucosa under the
blastocyst is decidua basalis; overlying it is decidua capsularis;
opposite, across the uterine lumen, is the decidua parietalis/vera.
3 Trophoblast encircles the embryonic germ disc, with its amniotic cavity,
yolk sac, and exocoelom.
4 Trophoblast has an inner layer of distinct cells - cytotrophoblast -
and an outer layer of fused cells - syncytiotrophoblast.
5 Syncytiotrophoblast extends out, interrupting maternal blood vessels,
thereby spilling blood into lacunar spaces within its own mass.
3 Formation of the placenta
l Trophoblastic layer proliferates, and takes on an additional
innermost mesenchymal layer, to constitute the chorion.
2 From the chorion, cords of trophoblasts extend out as primary chorionic
3 Mesenchyme of the extraembryonic mesoblast grows down inside these,
converting them to secondary villi.
4 The villi extend into spaces (intervillous) filled with maternal blood,
replenished via the uterine arteries and veins.
5 Peripherally, the distal tips of anchoring villi, composed of
cytotrophoblasts, unite to form a layer - trophoblastic shell -
covering the uterine decidua cells (except at the openings of maternal blood
6 Fetal blood vessels then appear in the cores of the villi, making them
tertiary, or definitive, placental villi.
7 These fetal vessels connect with the body stalk that will form the
umbilical cord to the embryonic vascular system.
8 Later, the villi that have grown all over the chorion: (a) grow and branch
basally to form the chorion frondosum, and eventually the discoidal
(b) over the rest of the surface towards the uterine cavity, villi shrink and
disappear (followed by the decidua capsularis) leaving the smooth chorion
9 Think of the placenta as two frisbies - chorionic plate and basal plate -
set against each other, face-to-face, creating a space for the maternal blood
and foetal villi.
On slides, the chorionic plate resembles umbilical cord, but on the uterine
side the thin basal plate has separated from the myometrium.
4 Placental villi
l Free villi branch out extensively from each stem villus. The whole
branching unit constitutes one of the fetal cotyledons.
2 Each tertiary villus has an:
3 Syncytiotrophoblast is unique in combining these talents:
- (a) outer syncytiotrophoblast layer of fused-together, basophilic,
hormone-secreting, and absorptive 'cells', with smooth and granular
ER, and a brush border (microvilli) on their maternal blood-facing surface;
- (b) cytotrophoblast layer of distinct Langhans' cells, paler
and reducing in number as time goes on; on a
- (c) basal lamina: the outer boundary of a
- (d) loose stroma of reticular fibres and ground substances, with
large Hofbauer vacuolated macrophages, and fibroblasts;
- (e) fetal blood vessels and capillaries with their BL and
unfenestrated endothelium; capillaries move nearer to the wall of
the villus, as gestation proceeds, and the stroma acquires more collagen.
- (f) The nature of the placental barrier between maternal and fetal
bloods thus changes somewhat during pregnancy.
.. (a) being invasive;
.. (b) forming both steroid and peptide hormones;
.. (c) performing metabolic transformations;
.. (d) participating in a barrier;
.. (e) absorbing and transporting materials.
5 Maternal-fetal junction
l Trophoblastic shell becomes the foetal part of the basal plate, in
contact with the maternal decidua basalis.
2 Plate subdivides into units - maternal cotyledons - separated by
septa, with perforations allowing some lateral passage of blood.
3 Blood spurts up out of the basal plate from spiral arteries into
the intervillous space, and drops down into venous outlets.
4 The chorionic plate faces the basal plate as the other boundary to
the space for maternal blood. Just below the chorionic plate, where the septa
do not reach, is the open space of the subchorial lake.
5 Cytotrophoblasts persist in the basal plate, as cell islands, and in
the septa, and are often embedded in an eosinophilic, non-fibrous, intercellular
material - fibrinoid.
Basal fibrinoid provides a cleavage plane for separation of the
placenta at term.
6 Maternal decidua cells are large, with lipid and glycogen, lie in a
rich ground substance with reticular fibres, and perform steroid conversions.
7 Granulated endometrial-gland cells (K/Körnchenzellen) are an endometrial
kind of leucocyte, with acidophil granules. Present in the late secretory
phase, their numbers increase in the first-trimester decidua, so they may
somehow assist implantation.
6 Umbilical cord
l Enveloped in amnion and covered by simple, cuboidal, amniotic
epithelium, it consists of mucous CT - Wharton's jelly: a
gelatinous ground substance, with sparse collagen bundles and stellate
2 Located in the jelly are three umbilical blood vessels:
.. (a) One vein, with much muscle, but without valves and vasa vasorum.
.. (b) Two arteries, with thick, inner, longitudinal, and outer
circular muscle coats, no internal elastic lamina, and an insignificant
3 The jelly, the thick vessel walls, and their spiral course prevent kinking
and occlusion of the vessels.
4 Remnants of the (a) allantoic endoderm, and (b) yolk sac's stalk, with
vitelline vessels, may persist until quite late in pregnancy.