Female

Malbern

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HYPOTHALAMUS FEMALE REPRODUCTIVE ORGANS

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PITUITARY OVARY HYPOTHALAMUS FEMALE HORMONAL CONTROL progesterone CORPUS LUTEUM follicle stimulating hormone FSH releasing factors luteinizing hormone LH endometrial proliferation BREAST prolactin pitocin

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BREAST Sensory pathway for suckling reflex Myoepithelial cells Lactiferous sinus for milk storage Nipple Alveoli in lobules Multiple ducts dense Connective tissue Comprises much modified sweat glands in fatty CT Glands are distributed in lobules defined by bands of dense connective tissue Alveoli grow upon demand, then regress after lactation Several hormones are needed Multiple outlets increase mastitis risk Various tumors arise from alveolar, duct, andamp; myoepithelial cells

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HYPOTHALAMUS regulates andamp; times changes in circulating hormone levels for Menarche Ovulation Menstruation Gestation Parturition Lactation Suckling Menopause Reproduction has high energy demands. Cannot run continously at full bore. Thus, gaps and cycles.

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UTERINE TUBE STRUCTURES Ciliated andamp; secretory columnar epithelial cells Muscularis Serosa FUNCTIONS Catches oocyte Guides sperm andamp; egg together for fertilization Timed transport of developing zygote to uterus Nutrition of gametes andamp; zygote Think baseball mitt

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UTERINE TUBE: Regions Usual site of fertilization FIMBRIA INFUNDIBULUM AMPULLA ISTHMUS INTRAMURAL FIMBRIA means fringe andamp; applies to the whole rimof projections. ‘Fimbriae’ is incorrect: there is only one fringe, and the individual processes have no special name Cells andamp; uterus not to scale!

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UTERUS STRUCTURES Ciliated andamp; secretory columnar epithelial cells Simple glands in disposable lining (Endometrium) Strong Muscularis (Myometrium) Serosal covering FUNCTIONS Leads sperm to oocyte Receives andamp; nourishes blastocyst by: (a) adhesion (b) implantation (c) forming placenta Expels baby Expels placenta

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SECRETORY ENDOMETRIUM SPIRAL ARTERY Stratum basale Stratum functionale UTERINE GLAND Basal layer functions! It is not lost at menstruation, so it can provide the cells for regeneration of the mucosa Simple columnar epithelium

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Early Proliferative Breakdown involves enzymatic matrix digestion, apoptosis, andamp; altered blood flow Proliferative phase may be termed estrogenic/follicular from the driving hormone/source, likewise - secretory: progesterone/luteal phase narrow mucosa; straight glands; cellular stroma Menstrual shed ragged mucosa; crenulated dilated glands; loose stroma

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UTERUS CERVIX EO Transformation zone Stratified squamous epithelium replaces simple columnar - a metaplasia. The instability raises the cervical cancer risk. Hence, monitor any progression of change with Pap smears. CC Grips the opening to hold in baby. Ripens andamp; relaxes (fromrelaxin) at term

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FIBROIDS /Leiomyomas A Fibroid is a benign tumor of uterine smooth muscle (not of fibrous connective tissue), growing under the influence of gonadal hormones. Submucosal ones are most likely to cause endometrial bleeding.

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VAGINA STRUCTURES Stratified squamous epithelium Fibroelastic wall A thin Muscularis Adventitia FUNCTIONS By glycogen, specifies luminal microbial flora Receives penis andamp; permits penile movement Receives semen andamp; starts capacitation (boosting) Exit of baby

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VAGINA STRATIFIED SQUAMOUS EPITHELIUM wide LAMINA PROPRIA thin T MUSCULARIS T ADVENTITIA { { { Pale cells with glycogen NO GLANDS Characteristic - a lack of characteristics

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VULVA andamp; VESTIBULE STRUCTURES Skin or Stratified squamous epithelium Adipose and erectile tissues Sensory receptors Mucous vestibular glands FUNCTIONS Protective folds Erectile andamp; lubricated to facilitate penetration Rewarding sensations Exit of baby Micturition

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OVARY 1 STRUCTURES Covering epithelium Follicles to mature andamp; release the oocytes and to make hormones Stroma of special connective-tissue cells that can become glandular theca cells Glandular structures - corpora lutea Degenerating structures as part of the cycle of activity Central blood vessels CL

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OVARY 2 ENDOCRINE For genital andamp; breast development Determines womb’s endometrial state for receipt of the fertilized oocyte Maintains secretory state of the endometrium (decidua after implantation) Starts secretory processes in the breast Relaxes* uterine muscle, andamp; softens (ripens ) the cervical connective tissue at term Feedback to hypothalamus for overall timing [ * Relaxation during gestation also affect ureteric muscle, allowing some reflux andamp; infections to ascend to the kidney]

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OVARY 3 CYTOGENIC (cell making) Releases one or two oocytes periodically Reduces their chromosome number Introduces genetic variability Discards half the product of meiotic cell division Builds up reserves in the maturing oocyte Sends the oocyte on its way protected by zona pellucida andamp; attached granulosa cells (the corona radiata)

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OVARY 1 Background SURFACE EPITHELIUM Simple cuboidal andamp; squamous Sometimes makes cysts within the cortex STROMA somewhat denser under the epithelium STROMAL CELLS ‘fibroblastic’ with potential to: 1 secrete steroids 2 produce thick collagen - fibrosis 3 become decidual cells (ectopic pregnancy) 4 become Leydig cells (near hilus) MEDULLA with convoluted vessels entering at the hilus CORTEX

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OVARY 2 Players in the cortex MAIN PLAYERS: FOLLICLES GLANDULAR STRUCTURES REMNANTS Theca interna Granulosa lining Corpora lutea Atretic follicles Corpora albicantes Primordial Primary, secondary, tertiary Atretic (Corpus albicans X 2,3,)

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OVARY 3 Players in the cortex MAIN PLAYERS: FOLLICLES CORPUS LUTEUM CORPUS ALBICANS CORPUS ATRETICUM/ FIBROTICUM ‘White body’ - a fibrosed scar replacing a used CLM or CLP Primordial Primary, secondary, tertiary Atretic CLM Corpus luteum of menstruation CLP Corpus luteum of pregnancy small, pink (eosin), wriggly remnant of an atretic follicle All in all, a very diverse and changing range of cortical structures

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OVARIAN FOLLICLES andamp; follicular events Stromal cell specialization to become Theca interna Basal lamina Zona pellucida Granulosa cells making estradiol, etc 2o/PREANTRAL FOLLICLE 1o Oocyte Note - The follicle may be secondary or tertiary, but the oocyte remains primary until ovulation glycoprotein barrier

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loss to atresia overall 99.9% Primordial follicle (inactive) Primary follicle (activated by FSH) Secondary/Preantral follicle squamous follicular cells cuboidal multiplying granulosa cells enlarging oocyte developing zona pellucida Stromal-cell specialization - Theca interna Granulosa cells making estradiol, etc Zona pellucida loss to atresia

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Theca interna cells make androstenedione for Granulosa cells to convert to estradiol (aromatase) ANTRUM with Liquor folliculi Cumulus oophorus Theca externa Granulosa cells Theca interna 3o/Antral follicle 1o Oocyte

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OVULATORY EVENTS 1 Enlargement bring follicle close to surface of ovary 2 Surface epithelial cells andamp; stromal cells digest stroma and die 3 Oocyte +Zona pellucida+Corona radiata (adjacent granulosa cells) break loose and float in liquor folliculi 4 Stromal cells contract andamp; burst the follicle 5 Follicle ruptures and oocyte etc set forth 6 Oocyte completes meiosis I, with formation of the first polar body and its set of half the chromosomes - reduction division

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Graafian Follicle It was these large antral follicles that Reinier de Graaf (1672) saw, without microscopy, in rabbit ovaries. Although he thought that the whole follicle was the ovum, this was a considerable advance on the prevailing view that semen caused menstrual blood to turn into the egg as a solely uterine event! [von Baer first found the mammalian oocyte in 1827] Save this term for large antral follicles: Why? from Jay V. The legacy of Reinier de Graaf. Arch Pathol Lab Med 2000;124:1115-1116

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Organizing central blood clot CORPUS LUTEUM Small dark THECA LUTEIN CELLS GRANULOSA LUTEIN CELLS large, andamp; palely eosinophilic (like adrenal Zona- fasciculata cells) driven by LH to make progesterone, etc Fibroblast making reticular fibers Invading blood vessels Stroma folded-in because it arises from a collapsed structure

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CORPUS ALBICANS pale, slowly resorbing collagen,with a few fibroblasts Ovarian stroma Deprived of LH, Granulosa lutein cells die; then macrophages, fibroblasts andamp; vessels dominate, to ‘heal’ the site - shift of balance

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CORPUS LUTEUM Organizing central blood clot Small dark THECA LUTEIN CELLS GRANULOSA LUTEIN CELLS Fibroblast Invading blood vessels Stroma Corpus luteum of menstruation (CLM) Corpus luteum of pregnancy, driven by placental hCG: is larger than CLM; lasts longer; leaves a significant corpus albicans (scar); eventually superseded by placenta itself

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UTERUS OVARY VAGINA VULVA UTERINE TUBE HAZARD FOR PERITONEAL CAVITY There is no tissue barrier stopping microorganisms from outside the body reaching the peritoneum However, there are several mechanisms and devices to reduce the hazard

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Mechanisms andamp; devices to reduce the hazard Vaginal epithelial glycogen favors benign lactobacilli Pathway has constrictions andamp; is long andamp; often narrow Ciliary current is down the tube Mucosal andamp; peritoneal lymphocytic andamp; other defensive cells Mucus plug in cervix (needs to loosen around ovulation time andamp; at menses)

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VULNERABILITIES FROM WOMAN’S REPRODUCTIVE ROLE* INSTABILITY More problems of control than a steady state Infection risk e.g., osteoporosis Cancer risk HEAVY-DUTY INDUSTRIAL-SCALE ACTIVITIES hemorrhage andamp; infection can be massive locating trouble in large organs is difficult e.g., for breast cancer detection NUTRITION If marginal, may be pushed over the brink by demands of pregnancy andamp; lactation PHYSIQUE With high fat, low muscle, taken physical advantage of, e.g., HIV risk PSYCHOLOGICAL disturbed from endocrine readjustments e.g., low thyroid - post-partem depression low hormones after menopause - sometimes lowered energy andamp; mood Vulnerability to loss of fetus or child

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PLACENTA: plan LID UMBILICAL CORD Maternal blood TROUGH for HUGE EXCHANGE SURFACE from branching processes - chorionic villi - containing fetal capillaries fetch andamp; carry blood to fetus

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Fetal blood in capillary SYNCYTIOTROPHOBLAST no dividing cell walls CYTOTROPHOBLAST TERTIARY VILLUS Hofbauer MF Maternal blood Loose CT Endothelial cell Fetal RBCs are nucleated

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SYNCYTIOTROPHOBLAST FIBRINOID - a placental deposit of maternal-blood proteins, unrelated to fibrin In the basal plate, creates a cleavage plane for separation of the placenta is unique in combining these talents: being invasive forming both steroid and peptide hormones performing metabolic transformations participating in a barrier absorbing and transporting materials

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UMBILICAL CORD The smooth amniotic surface allows free movement The mucoid CT firmly cushions the vessels andamp; prevents kinking The cord has a mild spiral curvature which also prevents kinking andamp; obstruction of the vessels The thick vessels walls also have this effect, aside from controlling blood flow

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MA andamp; PA MEIOSIS Aim: From one 1o spermatocyte to produce four spermatids, each with: (i) 23 chromosomes (haploid #); (ii) each chromosome derived from either Ma or Pa; (iii) but with bits of Pa’s chromosome replacing some of Ma’s, and vice versa Think quartering cuts P M P M X23

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Meiotic division II Paternal 3 FOUR SPERMATIDS Centromere splitting Bivalent for crossing over of aligned chromatids DNA excison andamp; ligation @ Primary spermatocytes Paternal 3 { Maternal 3 { Meiotic division I Secondary spermatocytes DNA synthesis maternal andamp; paternal #3 chromosomes Each chromosome now a pair of chromatids held together by a centromere P { M { maternal-paternal homologue pairing MA andamp; PA MEIOSIS

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MA andamp; PA MEIOSIS DNA synthesis maternal andamp; paternal #3 chromosomes Each chromosome now a pair of chromatids held together by a centromere maternal-paternal homologue pairing

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Random assignment of maternal andamp; paternal chromosomes (disjunction)*, e.g., Paternal 123456 Maternal Paternal Paternal Paternal Maternal etc Maternal 123456 Paternal Maternal Maternal Maternal Paternal etc * Site of trouble Wrong assignment of chromosomes, e.g., 2 #21s to one 2o spermatocyte andamp; none to the other. Then + one from oocyte = Trisomy 21 in the zygote Meiotic division I

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Paternal 3 Maternal 3 Maternal 3 Paternal 3 OOCYTE OOCYTE MEIOSIS 1st POLAR BODY unity disunity OR 2nd POLAR BODY function dysfunction disjunction nondisjunction

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OVARY TESTIS OVARY OR Sex-determining Factor Default pathway Testosterone Mullerian-inhibiting Factor MULLERIAN DUCT WOLFFIAN DUCT UROGENITAL SINUS andamp; TUBERCLE Driven pathways : :

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OVARY Default pathway MULLERIAN DUCT WOLFFIAN DUCT regresses GENITAL TUBERCLE :

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WOLFFIAN DUCT regresses, except for UTERUS VAGINA VULVA UTERINE TUBE Epoophoron andamp; Paraoophoron Gartner’s cyst REMNANTS IN THE WOMAN Mesonephric :

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TESTIS Sex-determining Factor Driven pathways Testosterone Mullerian-inhibiting Factor MULLERIAN DUCT regresses WOLFFIAN DUCT UROGENITAL SINUS andamp; TUBERCLE Dihydrotestosterone SERTOLI CELL MALE FACTORS andamp; TARGETS IN SEXUAL DEVELOPMENT : :

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Sex-determining Factor/SRY DRIVEN PATHWAYS Testosterone Mullerian-inhibiting Factor MULLERIAN DUCT regresses Dihydrotestosterone PROSTATE PENIS SEMINAL VESICLE RETE TESTIS TUBULUS RECTUS EFFERENT DUCT EPIDIDYMIS DUCTUS DEFERNS BULBOURETHRAL GLAND urethra INTERSTITIAL CELLS SEMINIFEROUS TUBULE TESTIS WOLFFIAN DUCT UROGENITAL SINUS andamp;TUBERCLE : :

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PROSTATE PENIS SEMINAL VESICLE RETE TESTIS TUBULUS RECTUS EFFERENT DUCT EPIDIDYMIS DUCTUS DEFERNS BULBOURETHRAL GLAND urethra INTERSTITIAL CELLS SEMINIFEROUS TUBULE TESTIS WOLFFIAN DUCT UROGENITAL SINUS andamp;TUBERCLE REMNANTS IN THE MAN MULLERIAN DUCT regresses, except for Appendix testis Prostatic Utricle Paramesonephric