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Female Reproductive

Ovaries are paired organs covered by a single layer of cuboidal mesothelial cells and enclosed by the fibrous CT tunica albuginea. Two zones:

  • Outer cortex – contains follicles in various stages, and fibroblast stroma
  • Central medulla –dense stroma with nerves, veins and helical arteries

Follicular development – early in embryonic development, primordial germ cells migrate from the yolk sac to the cortex of the developing ovary as oogonia. They multiply and differentiate into immature oocytes. Follicles pass through several stages of development:

  • Primary (pre-antral) follicle – contains a central, immature ovum arrested in the first division of meiosis (primary oocyte), surrounded by a layer of squamous or cuboidal follicular epithelial cells (granulosa cells). Stromal cells nearest the follicle enlarge to form a layer called the theca interna, surrounded by the theca externa (a layer of CT cells). As the oocyte enlarges, a clear non-cellular zona pellucida surrounds it.
  • Secondary (antral) follicle – as the primary follicle enlarges to contain 8-12 layers of granulosa cells, small irregular fluid-filled spaces (vesicles) develop among the cells. These spaces coalesce to form a single cavity, the follicular antrum. The mature-sized oocyte is embedded in a mound of granulosa cells at the edge of the antrum, the cumulus oophorus. A small ring of granulosa cells, the corona radiata, is attached to the zona pellucida. The follicle is now about 8-10mm in diameter and has enlarged so it bulges from the surface of the ovary.
  • Mature (Graafian) follicle – at least 10-14 days is required for the primordial follicle to reach maturity. It is about 1cm in diameter. In ovulation, the mature ovum, ZP and corona radiata are released together.

Sequels of folliclesan ovarian follicle will transform into one or more temporary structures or sequels:

  • Corpus hemorrhagicum – transient, immediately following the rupture of the follicle at ovulation, a temporary blood clot forms in the collapsed follicle
  • Corpus luteum – (temporary) walls collapse inwards forming folds or pleats, with remaining granulosa cells caught between. These are transformed into cords of large, clear secretory cells (granulosa lutein cells). If the ovum is not fertilized, the corpus luteum persists for about 10-14 days before it undergoes involution; in pregnancy it will enlarge and remain functional for about 6 months.
  • Corpus albicans – irregular, pale scar; end product of the degenerating corpus luteum
  • Atretic follicles – at various stages of follicular development, before they become fibrous scars. The initial sign of atresia in the primary follicle is that the oocyte is shrunken, irregular and undergoing cytolysis

















Oviduct – common passageway for downward migration of the ova and upward movement of the spermatozoa.

  • Inner mucosa thrown into many folds. Simple columnar epithelium with two cell populations :
    • Ciliated cells with spherical nuclei and cilia that beat towards the uterus (more numerous)
    • Non-ciliated peg cells with larger ovoid nuclei. Assumed to be nutritive, mucoid, secretory cells.

The lamina propria has spindle-shaped stromal cells, CT cells, fibers (collagen and reticular), blood vessels and leukocytes. A delicate basal lamina is present but no muscularis mucosa and or submucosa

  • Muscularis of smooth muscle – inner circular and outer longitudinal layers
  • Serosa –thin layer of CT covered by mesothelium. Within the CT layer, blood vessels supply the muscularis and also form a plexus beneath the mesothelium. The nerves also form a plexus, supplying motor impulses to the muscularis and sensory stimuli to the mesothelium

Uterus

  • Endometrium – simple columnar epithelium with or without cilia, a wide lamina propria housing mucosal glands, and the endometrial stroma. It is divided into a basal third (stratum basalis) and luminal two thirds (stratum functionalis. In menstruation the stratum functionalis degenerates while most of the basal layer remains intact, which regenerates the new mucosa for the next cycle. It undergoes cyclic changes:
    • Proliferative phase – epithelial cells initially low columnar but gradually increase in height. The glands are short and straight, but increased in length and become lightly folded as the mucosa thickens. Blood vessels penetrate from the myometrium and produce a vascular stroma
    • Secretory phase – major changes in the stratum functionalis; most strikingly, the glands become dilated, coiled and filled with secretory materials (glycogen and mucus). Stroma swollen with fluid; coiled arteries increase in length and complexity
  • Myometrium – most of the thick wall of the uterus; composed of smooth muscle about 15-20mm thick. The thin outer and inner layers are mostly longitudinal or oblique fibers; thicker central layer is predominantly circular fibres
  • Perimetrium – thin, outermost serosal layer containing blood, lymph vessels, nerves and sympathetic ganglia.

Blood supply: branches of the uterine artery pass from the myometrium into the endometrium to divide into short, straight arteries that nourish the basal layer, and the (helicine) spiral branches that supply the functional layer. On withdrawal of progesterone during the late menstrual cycle, the spiral arteries constrict periodically, rendering the functional layer hypoxic and finally ischemic. The straight arteries remain intact, providing for regeneration. Cervix – divided into an upper portion (cervical canal) and the lower vaginal portion; epithelium is simple columnar. Layers are continuous with the uterus, but their histological components vary:

  • Cervical canal wall consists largely of dense collagenous and elastic fibers with only about 15% being smooth muscle
  • The mucosa contains complex mucous glands and deep branching folds (plicae palmatae), which respond to estrogenic stimulation. These may become occluded and form cysts.

Vagina –

  • Mucosa – longitudinal folds of the mucosa (rugae) extend throughout relaxed vagina, lined by stratified squamous, nonkeratinised epithelium. The epithelial cells contain glycogen which is acted upon by bacteria to produce lactic acid. The lamina propria contains many elastic fibers, a few small lymph nodules and various leukocytes
  • Muscularis – two poorly defined smooth muscle layers. Thin inner layer fibers are circular, outer thicker layer are longitudinal and continuous with the myometrium of the uterus
  • Adventitia – dense CT layer surrounding the vagina and blending with adjacent organs. It has considerable elastic tissue. Blood vessels, nerves and lymphatics traverse this region to supply the inner layers of the vagina.



Mammary gland – modified sweat glands; each is a collection of 10-20 entirely separate glands (lobes), arranged in a radial fashion around each nipple. Each lobe has a lactiferous duct that widens into a sinus before it opens on the summit of the nipple. The parenchymal tissue consists of a series of ducts and acini (alveoli) lined with simple cuboidal or low columnar epithelium and partially surrounded by myoepithelial cells. The lobe stroma is loose CT, infiltrated with abundant adipose cells and collagen fibers.












Male reproductive

Testis, rete testis and seminiferous tubules Seminiferous tubules – wall consists of 4-5 layers of the epithelial spermatogenic (sex) cells with intervening angular Sertoli cells. The most basal of these cells are the spermatagonia, followed by primary spermatocytes, secondary spermatocytes and bordering the lumen of the tubules, the spermatids and spermatozoa.

  • Spermatagonia are primitive diploid stem cells. They are ovoid or spherical, and rest on the ST's basal lamina
  • Spermatagonia undergo mitosis, move away from the basal lamina, increase in size and divide by meiosis to form the spermatocytes after the first division and spermatids after the second (round/elongated cells, luminal)
  • Spermiogenesis is the dramatic transformation of a spermatid into a mobile, slender, mature spermatozoon which a long flagellum

Interstitial Leydig cells cluster between the seminiferous tubules and produce testosterone.

Efferent ducts and epididymis

  • Ductuli efferentesextend from the rete testes to the head of the epididymis; 10-15 twisting tubules. The lumen is heavily folded, with a ciliated columnar epithelium
  • Ductus epididymisas the efferent ductules enter the head of the epididymis, they fuse into a single, highly coiled tube. It has a pseudo stratified columnar epithelium with stereocilia. The stereocilia are like long microvilli; they function to increase surface area for fluid absorption (90%), which clumps the sperm. The epididymis also functions for storage and maturation of the sperm, they leave fully motile.




Ductus (vas) deferens –same epithelium as epididymis; functions to conduct sperm onwards





Seminal vesicles – each lumen is tightly packed with folds of the mucosa, lined with pseudo stratified columnar epithelium. Muscularis has a thin inner and thicker outer longitudinal muscle layer. A thin fibroelastic adventitia encloses the gland

Prostate – enclosed by a robust, fibromuscular capsule with septa that pass inward to divide the gland into lobules. The capsule is significant, as it initially contains prostatic carcinoma. The stroma is mostly smooth muscle fibres, richly laced with collagenous and elastic fibres. Alveoli are lined with simple cuboidal to low columnar or pseudo stratified columnar cells.

Penis – 3 prominent cylinders of erectile tissue. Dorsally are the two corpora cavernosa, incompletely separated by a sagittal septum. The single corpus spongiosum, containing the penile urethra lies ventrally. Abundant nerve endings (e.g. Meissner's and Pacinian corpuscles) are associated with the skin of the penis.




Placenta and fetal membranes

The placenta and fetal membranes (chorion, amnion, yolk sac, allantois) separate the fetus from the endometrium.

Umbilical cord – twisted, as the umbilical vessels (fetal circulation) are longer than the cord. Placenta – has a fetal component (chorionic villi) and maternal component (decidual basalis)

Fetal chorionic villi covering the chorionic sac attach and invade the decidua basalis, eroding the decidual tissue to enlarge the intervillous space. This produces placental septa that divide the fetal part into cotyledons, each consisting of two or more more stem villi and the many branch villi arising from them. The intervillous space contains maternal blood from the spiral endometrial arteries; showers the branch villi

There are two main types of early villi – anchoring villi attached to [decidua-http://php.med.unsw.edu.au/embryology/index.php?title=D] and floating villi in the maternal [lacunae-http://php.med.unsw.edu.au/embryology/index.php?title=L]. Stages of development:

After implantation, the endometrium undergoes a decidual reaction. Decidual cells are large pale-staining cells with a prominent central pale nucleus and basophilic nucleus. The maternal side also contains dark extracellular protein (fibrinoid). The decidua is named according to its relation to the implantation site –

  • Basalis – deep to the conceptus
  • Capsularis – superficial, overlying the conceptus
  • Parietalis – all remaining parts, not in contact with fetus









Chronic inflammation

Inflammation of a prolonged duration (arbitrary >6 weeks) in which active inflammation, tissue injury and healing proceed simultaneously; characterised by:

  • Infiltration with mononuclear cells – macrophages, lymphocytes, plasma cells
  • Tissue destruction, largely induced by the products of the inflammatory cells
  • Repair, involving angiogenesis and fibrosis

It may be due to an acute irritant which is not eliminated, for example persisting acute infections, or many autoimmune diseases. Alternatively, some forms of injury (such as foreign bodies, some viral infections) engender a response that involves chronic inflammation from the outset (i.e. low intensity irritant of long persistence).

Macrophages are the dominant cells of chronic inflammation; derived from circulating blood monocytes. In all tissues, macrophages act as filters and sentinels to alert lymphocytes. Macrophages may become activated by cytokines or microbial products (e.g. endotoxin), resulting in increased cell size, metabolism, content of lysosomal enzymes and ability to kill ingested organisms. They appear large and flat under microscopy, and so sometimes called epithelioid cells. They may also fuse into large multinucleated giant cells.

Granulomatous infection is a distinctive pattern of chronic inflammation, characterised by aggregates of activated macrophages. Granulomas wall off the offending agent, and therefore are a useful defence mechanism. However, they do not always lead to eradiation of the causal agent; granulomatous inflammation with subsequent fibrosis may even be a major cause of organ dysfunction in some diseases (e.g. tuberculosis). Granulomas contain epithelioid cells with pink, granular cytoplasm, and frequently giant cells. Aggregates of macrophages are surrounded by lymphocytes secreting the cytokines responsible for continuing macrophage activation. Older granulomas may have a rim of fibroblasts and CT. In granulomas associated with certain organisms, a combination of hypoxia and free-radical damage leads to a central zone of caseous necrosis (amorphous, structureless, granular debris)

Long term consequences of chronic inflammation

  • Continuing effects of acute inflammation
  • Destruction of tissue; scarring
  • Systemic effects – activation of proinflammatory cytokines (especially TNFα and IL-1), released systemically causes the acute phase response