HISTOLOGY FULL-TEXT

William A Beresford MA, D Phil ©
Professor of Anatomy
Anatomy Department, West Virginia University, Morgantown, USA

Chapter 29 FEMALE REPRODUCTIVE SYSTEM

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
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A OVARY

l General structure
l Covered by mostly simple epithelium (variably columnar, cuboidal, or squamous),
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 masses.
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            |
                          |
                      Corpus luteum
                       /             \
                      /               \
          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
                          \         /
                           \       /
                            \     /
                       Corpus albicans
                      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

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.)

3 Changes in stroma around maturing follicle

4 Ovulation

5 Corpus luteum: formation, function and fate

6 Signs of follicular atresia (aborted development)
.. (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, longitudinal bundles.
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.

C UTERUS

l Outer serous coat (perimetrium), with vessels, nerves, and ganglia.

2 Myometrium of interwoven smooth muscle, capable of a great hypertrophy during pregnancy, with many blood vessels in the middle stratum vasculare.

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:

  1. It has more collagen and elastic in the wall than muscle.
  2. Mucosa is furrowed by complex clefts - plicae palmatae; and does not participate in menstruation.
  3. Lining columnar epithelial cells produce a mucus, richly hydrated and penetrable at mid-cycle.
  4. 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.

D VAGINA

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 and labia.
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 Structure
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.

2 Nipple
l Cornified stratified squamous epithelium covers a stroma of elastic fibres, smooth muscle, and collagen, through which pass the lactiferous ducts.
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.

3 Histophysiology
l Prepubertal period
.. (a) Nipple remains small and weakly pigmented.
.. (b) Glands stay rudimentary as multiple, branched, tubular units in a CT stroma.
2 Puberty
.. (a) Oestrogen promotes ductal growth, and the formation of stromal adipose tissue.
.. (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

5 Lactation
(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 parturition.
(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

G PLACENTATION

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.

2 Implantation/nidation
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 villi.
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 vessels).
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 placenta;
(b) over the rest of the surface towards the uterine cavity, villi shrink and disappear (followed by the decidua capsularis) leaving the smooth chorion laeve.
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) 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 fibroblasts.
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 adventitia.
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.


William A Beresford, Anatomy Department, School of Medicine, West Virginia University, Morgantown, WV 26506-9128, USA - - e-mail: -- wberesfo@wvu.edu -- wberesfo@hotmail.com -- beresfo@wvnvm.wvnet.edu -- fax: 304-293-8159