Main components of female reproductive system A. Ovaries B. Uterine tubes C. Uterus D.

Mammary gland Ovary: Produces oocytes -oogenesis Produces female sex hormones: o Oestrogens (theca interna cells) o Progesterone (CL) o Inhibin (granulosa cells)

Uterine tubes: Conducts ova towards uterus Site of fertilisation Uterus: Vagina: Site of intoduction of spermatozoa Birth canal Site of implantation

Co-ordination of function due to Hypothalamic-pituitary axis Secretory status of tissues/organs The timing of secretion and the sites of action of hypothalamic, pituitary and ovarian hormones are essential to understanding the physiology of reproductive function. A: Ovary Three histological regions: 1. Cortex: Cellular region: o Follicles = oocyte + follicular/granulosa cells stroma Fibroblasts + collagen types I and III 2. 3. Medulla: loose ct, bvs, nerves Hilum: stalk-like region of entry/exit of bvs + nerves, ct

Oocytes Develop in the embryo ~6 weeks Primordial germ cells from yolk sac colonise embryonic gonad. Mitosis of primordial germ cells oogonia several million 1 - 2 million at birth ~400,000 at puberty ~400 will ovulate, the rest become atretic (will degrade)

 Oogonia meiosis 1 primary oocyte First meiosis arrested at prophase I / diplotene until recruitment for ovulation (up to 45 - 50 years)

At puberty monthly cycles commence: Primary oocyte completes meiosis 1 secondary oocyte Secondary oocyte begins meiosis 2 ovulated ovum, arrested in metaphase II Fertilisation by sperm completes meiosis 2 zygote Follicles Follicle = oocyte + follicular/granulosa cells From birth to menopause follicles divide into two groups: 1. 2. Non-growing follicles Growing follicles

Non-growing follicles Essentially form a stockpile of oocytes arrested at prophase I 1. Primordial follicles - flat granulosa cells 2. Intermediate follicles 3. Primary follicles - cuboidal granulosa cells Growing follicles 1-15 non-growing primary follicles become growing follicles every day Growing follicles Primary follicle secondary follicle 1. Development of zona pellucida 2. Development of theca theca interna secretes oestrogen o Primary and secondary follicles are pre-antral follicles o LH induces theca interna cells to convert progesterone androgen o FSH induces granulosa cells to convert androgen oestrogen o Several follicles develop each month, although only one becomes dominant and is ovulated. This is necessary in order to develop sufficient oestrogen to prepare the uterus for implantation. Antral and Graafian follicles o Secondary follicles enlarge by formation of antrum (may be called tertiary follicles) o Secondary oocyte sits in the antrum, surrounded by zona pellucida and a narrow stalk of granulosa cells (cumulus oophorus) o Tertiary follicles may appear in embryo, and subsequently undergo atresia

Ovulatory cycles begin ~6 months after menarche

Ovulation Largest Graafian follicle completes meiosis I 24 hrs before ovulation o Meiosis secondary oocyte + tiny polar body o Secondary oocyte meiosis II (arrests at metaphase II)

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Primary follicles take 90 days to reach ovulation All except one become atretic The dominant tertiary follicle becomes more sensitive to gonadotrophins (LH + FSH) due to increased expression of receptors (in response to oestrogen) High levels of oestrogen secretion feeds back to pituitary oestrogen GnRH FSH + LH surge rupture and ovulation

Corpus luteum Granulosa and thecal cells of ruptured follicle become granulosa and theca lutein cells of CL CL becomes richly vascularised LH causes granulosa cells to secrete progesterone, oestrogen, and others Fate of CL depends on whether implantation has occurred No implantation luteolysis CL degenerates within 2 weeks Fibrosis, pigmentation (haemoglobin) corpus nigricans Hyalinisation, white ct corpus albicans Ultimately resorbed into stroma If implatation does occur the corpus luteum is sustained for several weeks by hCG. Loss of ovarian hormones allows resumption of follicular development Ovary not CNS controls normal monthly cycle

Implantation Developing placenta secretes hCG HCG prevents luteolysis, & stimulates luteal cells to produce progesterone. After 5 - 6 weeks placental progesterone and oestrogen production takes over from CL (luteal-placental shift). the CL may regress after about 10 weeks What you should be able to identify Ovarian cortex, medulla, hilum. Basic components, ct, bvs, nerve Primordial follicles: oocyte + follicular cells Primary follicles: oocyte + granulosa cells Secondary follicles: oocyte + granulosa cells + zona pellucida + theca Antral follicles: oocyte + granulosa cells + zona pellucida + theca + antrum Corpus luteum Corpus albicans (corpora albicantes)

B: Uterine tubes From ovary to uterus: o Funnel-shaped at ovarian (distal) end o Tapers towards uterus Muscular tube lined with mucosa Mucosa is simple columnar/cuboidal ciliated, secretatory epithelium.

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Distal end Mucosa (endosalpinx): highly branched and folded ciliated columnar cells - transfer ovum from ovary to uterine tube secretory cells - supply nutrients to ovum/zygote: o pyruvate, glucose, amino acids, proteins Apocrine and exocytotic secretion Look a bit like goblet cells Muscle coat (myosalpinx) Two indistinct layers, relatively thin.

2.

Proximal end Endosalpinx narrow lumen short longitudinal folds ciliated columnar/cuboidal cells secretory cells Myosalpinx thick three indistinct layers

Secretory activity of the uterine tubes is maximal at midpoint of cycle (ovulation) Sperm pass along tube within hours, assisted by peristalsis and sperm motility Zygote passage ~ 3 days (in opposite direction).

C: Uterus Muscular tube lined with mucosa which undergoes cyclical changes Mucus is a simple, columnar epithelium with glands. Myometrium 1. smooth muscle - three indistinct layers 2. CT: collagen + elastic fibres Marked hypertrophy + hyperplasia during pregnancy Contracts during labour to expel fetus. Endometrium 1. thick mucosa 2. tubular glands extending down from surface into stroma Deepest 1/3 = stratum basalis Upper 2/3 = stratum functionalis (stratum compactum + spongiosum) Stratum functionalis 1. Undergoes cyclical growth and degeneration 2. Regenerates from stratum basalis Rich in glycogen to provide nutrition for implanting zygote.

Endometrium and menstrual cycle Regulated by ovarian steroids Follicular phase: proliferative phase Estrogen from ovaries during follicular phase induces proliferation of endometrium Endometrium doubles in thickness Increase in growth and height of mucosal tubular glands Luteal phase: secretory phase Progesterone from corpus luteum induces glandular maturation Coiling and lengthening of rich vascular supply (spiral arteries and veins) Day 21 of menstrual cycle Superficial mucosa deciduates Stromal cells proliferate into cuboidal deciduous cells Abundant leucocytes Menstruation is inevitable if no implantation Luteolysis: menstrual phase Withdrawal of hormone support leads to changes in endometrial vascular supply Hypoxia causes degeneration Products of menses: non-clotted blood, dead/dying tissue, fluid Stratum basalis remains to regenerate stratum functionalis. Vagina (= sheath) Stratified squamous epithelium (non-keratinised) Stroma of connective tissue (loose) with rich vascular plexus: o Collagen fibres + fibroblasts o Smooth muscle (very limited) o Blood vessels o Lymphatics o Nerve (fibres and occasional ganglia). Cervix: Simple epithelium Pronounced junction between the stratified squamous epithelium of the vagina, and the simple epithelium of the cervix the transformation zone. Frequenct site of malignancy. Disorders Uterine tube o Salpingitis Infection / inflammation of the fallopian tubes Mucosal fusions + adhesions blockage Common infectious agents: Chlamydia trachomatis Neisseria gonorrhoeae Sexually transmitted diseases (STDs) commonly cause female infertility Blocked/dysfunctional tubes can cause: Ectopic pregnancy Extrauterine implantation of embryo

Uterus o Hyperplastic endometrium Excessive oestrogen production cystic, adenomatous transformation or malignancy Common causes: Chronic anovulation Polycystic ovary syndrome Persistent dominant follicle Hormone-producing ovarian tumours o Endometriosis: Glands and stroma arise outside uterus Severe period pain (dysmenorrhoea) Infertility Abnormal cellular differentiation of peritoneal lining or retrograde menstruation.

D: Mammary gland Mature breast o Connective tissue divides breast into Lobules of secretory acini or alveoli Intralobular ducts (collect into lactiferous sinuses that empty into the nipple). 1. Resting state (non-lactating) Small amount of glandular tissue Predominance of ducts rather than alveoli. 2. Pregnant state Reduction of stroma (loose connective tissue) at the expense of glandular expansion Hypertrophy / hyperplasia of glandular tissue Increase in secretory alveoli Dilatation of alveoli by colostrum Distension of lobules Oestrogen induces duct proliferation Progesterone induces alveolar proliferation. 3. Lactating state 2 - 3 days post partum prolactin stimulates milk production o apocrine secretion (lipid droplets) o exocytosis (protein and carbohydrate) Intralobular septa not visible Interlobular ct reduced to strands due to massive expansion of glands and ducts

Cell-types in mammary glands 1. Stromal tissue ct: fibroblasts + collagen

bvs o intima endothelial cells o media smooth muscle ducts: cuboidal epithelium one or two layers nerve (not a lot) glial cells (Schwann cells) lymphatics

2. Lobular tissue Acini / alveoli: o Cuboidal epithelium o Myoepithelial cells Ct, bvs, nerve, lymphatics.

FEW NOTES ON MALE REPRODUCTIVE SYSTEM: Functions: o Formation, nuture and storage of sperm o Introduction of sperm to the female reproductive tract o Production of androgens Compontents of male reproductive system:

Never see secondary spermatocytes

Fibrous capsule o Tunica albuginea - gives rise to fibrous septae that separate testes into 200+ lobules Seminiferous tubules o Tightly packed into lobules of testes. o Tubules lined by multilayer germinal epithelium. o Each tubule 0.1-0.2 mm diameter up to 100 cm long. o Spermatogenesis (formation of spermatids) + spermiogenesis (maturation to spermatozoa) occur in co-ordinated waves along each tubule. Sertoli cells rest on basement membrane of tubules and support development of spermatic cells via complex cytoplasmic processes

Interstitial (Leydig) cells: o Found in spaces between tubules close to capillaries - secrete androgens (mainly testosterone) in response to luteinising hormone from pituitary. o Local concentrations of androgens therefore very high in testes

Gametogenesis: Spermatogonia o Primitive germ cells (present in small numbers before puberty) o Multiply by mitosis to give continuous supply of cells for meiosis Primary spermatocytes o Produced by mitotic divisions of spermatogonia o Undergo the meiosis I o They are easy to see because process takes ~3 weeks Secondary spermatocytes o Daughter cells of meisosis I o Hard to see because they rapidly undergo meiosis II to produce spermatids o will never see secondary spermatocytes in histological sample Spermatids o ~7 week maturation process (called spermiogenesis) to produce spermatozoa. Spermatozoa o Undergo the final stages of maturation in epididymis

Spermatozoa: Acrosomal cap o vesicle containing cocktail of enzymes (esp. hyaluronidase) to break up cells surrounding ovum and dissolve zona pellucida for fertilisation Nucleus o

containing half complement (haploid number) of chromosomes

Neck o contains residual cytoplasm

Middle piece o first part of flagellum (tail) containing Usual 9 + 2arrangement of microtubules as seen in cilia (axoneme) + 9 longitudinal coarse fibres + close-packed mitochondria Principal piece o Remainder of tail containing Usual 9 + 2arrangement of microtubules seen in cilia (axoneme) + 9 longitudinal coarse fibres o Tapering to end piece

Epididymisis A very long, convoluted duct leading from testes to vas deferens. Site of storage / maturation of spermatozoa (motility develops here). Smooth muscle at distal end has sympathetic innervation and contracts during ejaculation Vas (ductus) deferens A thick walled smooth muscular tube that transports spermatozoa to urethra; Sympathetic innervation intense contractions during ejaculation
Prostate gland

Large gland surrounding bladder neck + first part of urethra Glandular epithelium is irregular pseudostratified / columnar Glandular units produce thin milky fluid that make up 50% of seminal fluid volume. Enzymes in prostatic fluid (esp. fibrinolysin) liquefy coagulated semen some time after ejaculation Glandular units surrounded by supporting tissue which is a mixture of smooth muscle + fibrous tissue. Contracts in synchrony with other parts of the genital tract to expel glandular contents during ejaculation (sympathetic innervation) Increases in size (hypertrophy) with age due to androgen stimulation. Growth of innermost part may constrict urethra, reducing urinary outflow. Hypertophy of outermost part may lead to malignant transformation - prostate carcinoma is most common male malignancy (~10% of men affected) Prostatic concretions-calcified lumps -common in lumen of glands, esp. in older men

Seminal vesicles Glands formed by long (~15 cm), convoluted tubular outgrowths from ductus deferens Responsible for 50% of volume of seminal fluid Thick yellowish-white secretion containing: o Fructose o Proteins o Amino acids

o Prostaglandins o Citric o Ascorbic acids Thick smooth muscle wall contracts in synchrony with other partsof the genital tract to expel glandular contents during ejaculation (sympathetic innervation)

Penis Contains 3 cylinders of erectile tissue: o 2 x dorsal (corpora cavernosa) o 1x ventral (corpus spongiosum). Erectile tissue contains large, irregular vascular channels, lined by endothelium; surrounded by fibrous tissue with some smooth muscle bundles Parasympathetic nervous stimulation causes partial closure of normal a-v shunt and diversion of blood from helicene arteries into cavernous spaces; outflow of blood is restricted because thin-walled veins are compressed Corpus spongiosum becomes somewhat less turgid, allowing urethra to remain sufficiently open for passage of semen during ejaculation.