ENDOCRINE

REPRODUCTIVE

HISTOLOGY

FEMALE HISTOLOGY

Overview

• The female reproductive system consists of the paired ovaries and

oviducts (or uterine tubes), the uterus, the vagina, and the external

genitalia.

• This system produces the female gametes (oocytes), provides the

environment for fertilization, and holds the embryo during its complete

development through the fetal stage until birth.

Ovary

• Ovaries are almond-shaped bodies approximately 3 cm long, 1.5 cm

wide, and 1 cm thick.

• Mucosa:

• Each ovary is covered by a simple cuboidal epithelium continuous with the

mesothelium and overlying a layer of dense connective tissue capsule, the

tunica albuginea, like that of the testis.

• Most of the ovary consists of the cortex, a region with a stroma of highly

cellular connective tissue and many ovarian follicles varying greatly in size after

menarche.

• The most internal part of the ovary, the medulla, contains loose connective

tissue and blood vessels entering the organ through the hilum from

mesenteries suspending the ovary.

Primordial follicles are the only follicles

present at birth.

Follicles

• Beginning in puberty with the release of follicle-stimulating hormone

(FSH) from the pituitary, a small group of primordial follicles each

month begins a process of follicular growth.

• Primordial: Simple squamous cells

• Unilaminar: Single layer of cuboidal cells

• Multilaminar: Multiple layers of cuboidal cells, Zona Pellucida

• Antral: Fluid filled antrum, oocyte on one side, Cumulus oophorus, corona radiata

• Mature (Graafian): Dominant follicle, Large (full thickness of cortex), Oocyte &

corona radiata detach from cumulus oophorus, Hours before ovulation primary

oocyte (prophase I) becomes secondary oocyte (metaphase II)

• All follicles except the mature follicle contain primary

oocytes.

The zona pellucida is complete in the

multilaminar follicle and contains

glycoproteins ZP3 and ZP4 that are

critical for fertilization.

Follicular Atresia

• Most ovarian follicles undergo the degenerative process called atresia, in which follicular cells and oocytes die and are disposed of by phagocytic cells.

• Follicles at any stage of development, including nearly mature follicles, may become atretic.

• Atresia involves apoptosis and detachment of the granulosa cells, autolysis of the oocyte, and collapse of the zona pellucida.

• Early in this process, macrophages invade the degenerating follicle and phagocytose the debris, followed later by fibroblasts.

• Although follicular atresia takes place from before birth until a few years after menopause, it is most prominent just after birth, when levels of maternal hormones decline rapidly, and during both puberty and pregnancy, when qualitative and quantitative hormonal changes occur again.

Atresia

Connective Tissue Sheaths

• Theca Interna

• The theca interna (TI) surrounds the

follicle, its cells appearing vacuolated

and lightly stained because of their

cytoplasmic lipid droplets, a

characteristic of steroid-producing

cells.

• Theca Externa

• The overlying theca externa (TE)

contains fibroblasts and smooth

muscle cells and merges with the

stroma (S).

• A basement membrane (BM)

separates the theca interna from

the granulosa, blocking

vascularization of the latter

Production of Estradiol

• Role of Theca Interna in the production of Estrogen

• Theca interna cells receive LH signals from the blood

• Theca interna cells convert cholesterol into Androstenedione

• Androstenedione is secreted to the follicular cells

• Follicular cells (Granulosa Cell) convert Androstenedione into

Estradiol (via 5 alpha aromatase)

Ovulation

• Ovulation is the hormone-stimulated process by which the oocyte is released from the ovary. Ovulation normally occurs midway through the menstrual cycle, that is, around the 14th day of a typical 28-day cycle

• Just before ovulation the oocyte completes the first meiotic division, which it began and arrested in prophase during fetal life

• In the days preceding ovulation, the dominant vesicular follicle secretes higher levels of estrogen which stimulate more rapid pulsatile release of GnRH from the hypothalamus LH surge• Meiosis I is completed

• Granulosa cells produce hyaluronan

• Ovarian wall weakens

• Smooth muscle contractions

• Oocyte is expelled

Mature dominant follicle bulging against

the tunica albuginea develops a whitish or

translucent ischemic area, the stigma, in

which tissue compaction has blocked

blood flow

Corpus Luteum

• The corpus luteum is a large endocrine structure formed from the remains of the large dominant follicle after it undergoes ovulation

• Follicular cavity fills with blood and connective tissue

• Granulosa lutein cells undergo significant hypertrophy, producing most of the corpus luteum's increased size and producing progesterone.

• The theca lutein cells increase only slightly in size, are somewhat darker-staining than the granulosa lutein cells, and continue to produce estrogens.

• The ovulatory LH surge causes the corpus luteum to secrete progesterone for 10 to 12 days.

• Without further LH stimulation and in the absence of pregnancy, both major cell types of the corpus luteum cease steroid production and undergo apoptosis, with regression of the tissue after 14 days.

Corpus Luteum

Corpus Albicans

• After 14 days if there is no fertilization, the major cell types of the

corpus luteum cease steroid production and undergo apoptosis, with

regression of the tissue.

• A consequence of the decreased secretion of progesterone is

menstruation, the shedding of part of the uterine mucosa.

• After the corpus luteum degenerates, the blood steroid concentration

decreases and FSH secretion increases again, stimulating the growth

of another group of follicles and beginning the next menstrual cycle.

• Remnants from regression are phagocytosed by macrophages, after

which fibroblasts invade the area and produce a scar of dense

connective tissue called a corpus albicans

Corpus Albicans

Fertilization Effects

• If pregnancy occurs, the uterine mucosa must not be allowed to undergo menstruation because the embryo would be lost.

• To prevent the drop in circulating progesterone, trophoblast cells of the implanted embryo produce a glycoprotein hormone called human chorionic gonadotropin (HCG) with targets and activity similar to that of LH.

• HCG maintains and promotes further growth of the corpus luteum, stimulating secretion of progesterone to maintain the uterine mucosa.

• The corpus luteum of pregnancy becomes very large and is maintained by HCG for 4 to 5 months, by which time the placenta itself produces progesterone (and estrogens) at levels adequate to maintain the uterine mucosa. It then degenerates and is replaced by a large corpus albicans.

Uterine Tubes

• Structure• Mucosa

• Highly folded simple columnar epithelium (except ectocervix)

• Ciliated cells transport sperm and/or egg

• Secretory peg cells, nonciliated and darker staining secrete glycoproteins of a nutritive mucus film that covers the epithelium (Capacitation factors)

• Underlying lamina propria of connective tissue (a.k.a. “stroma”)

• Muscularis• Thick, well-defined muscularis with interwoven circular (or spiral) and

longitudinal layers of smooth muscle

• Serosa (peritoneum) or adventitia• Thin and covered by visceral peritoneum with mesothelium

• Function• Receives secondary oocyte from ovary

• Transports sperm, oocyte, zygote

• Provides appropriate environment for fertilization and zygote

Mucosa of Uterine Wall

Fertilization• Fertilization normally occurs in the ampulla of a uterine tube. Only sperm that

have undergone capacitation in the female reproductive tract are capable of fertilization.

• Capacitation• Acrosomal reaction: Upon contact with cells of the corona radiata, sperm undergo the

acrosomal reaction. This allows sperm to move more easily to the zona pellucida.

• Binding: Proteins on the sperm surface bind the receptors ZP3 and ZP4, activating the protease acrosin on the acrosomal membrane to degrade the zona pellucida locally.

• Cortical Reaction: The first sperm penetrating the zona pellucida fuses with the oocyte plasmalemma and triggers Ca2+ release from vesicles, which induces exocytosis of proteases converting the zona pellucida to the impenetrable perivitelline barrier that constitutes a permanent block to polyspermy.

• Fusion of the two pronuclei yields the new diploid cell, the zygote

• Cell division occurs while the embryo is transported by contractions of the oviduct muscularis and ciliary movements to the uterus, which takes about 5 days.

Migration

• Zygote undergoes mitotic cleavages as it is moved to the uterus, with its cells (blastomeres) in a compact aggregate called the morula.

• No growth occurs during the period of cell cleavage blastomeresbecome smaller at each division.

• 5 days after fertilization the embryo reaches the uterine cavity and the embryo enters the blastocyst stage of development.

• The blastomeres then arrange themselves as a peripheral layer called the trophoblast around the cavity, while a few cells just inside this layer make up the embryoblast or inner cell mass.

• The blastocyst remains in the lumen of the uterus for about 2 days, immersed in the endometrial glands' secretion on the mucosa.

Women with immotile cilia syndrome are

still fertile, presumably because of the

smooth muscle serving as a backup

system.

Implantation

• The embryo enters the uterus as a blastocyst about 5 days after ovulation or fertilization, when the uterus is in the secretory phase and best prepared for implantation.

• To begin implantation, receptors on cells of the outer embryonic trophoblast bind glycoprotein ligands on the endometrial epithelium.

• The trophoblast forms an invasive, outer syncytial layer called the syncytiotrophoblast.

• Proteases are activated and/or released locally to digest stromacomponents, which allows the developing embryo to embed itself within the stroma.

• The newly implanted embryo absorbs nutrients and oxygen from the endometrial tissue and blood in the lacunae.

Placenta

• The placenta is the site of exchange for nutrients, wastes, O2, and CO2 between the mother and the fetus and contains tissues from both individuals.

• The embryonic part is the chorion, derived from the trophoblast and the maternal part is from the decidua basalis.

• Exchange occurs between embryonic blood in chorionic villi outside the embryo and maternal blood in lacunae of the decidua basalis.

• Suspended in pools of maternal blood in the decidua, the chorionic villi provide an enormous surface area for metabolite exchange.

• Exchange of gases, nutrients, and wastes occurs between fetal blood in the capillaries and maternal blood bathing the villi, with diffusion occurring across the trophoblast layer and the capillary endothelium.

Placenta

The placenta is also an endocrine organ

roducing HCG, a lactogen, relaxin, and

various growth factors, in addition to

estrogen and progesterone.

Syncytial trophoblast

•Cytotrophoblasts

•Undifferentiated cells

•Divide and fuse to form syncytiotrophoblast

•Decrease in number with time during

pregnancy

•single layer discontinuous layer

scattered cells

•Syncytial trophoblast

•Continuous multinucleated layer

•Transports materials in both directions

•Endocrine organ

PlacentaCytotrophoblast

Placental Barrier

• Endothelium of fetal capillaries

• Basal lamina of fetal capillaries

• Mesenchyme of the placental villus

• Basal lamina of the trophoblast

• Cytotrophoblast (early in pregnancy only)

• Cytoplasm of the syncytiotrophoblast

Ectopic Pregnancy

• Ectopic pregnancy: implantation and development of an embryo outside the uterine cavity; most common location is in the uterine tube

• Pelvic inflammatory disease causes inflammation of the uterine tube and subsequent deposition of fibrous tissue and fusion of tubal folds

• This increases the risk of ectopic pregnancy by delaying the passage of the oocyte/zygote through the uterine tube

• Embryo can develop normally for a while, but rarely survives more than a few months; surgical intervention is required to remove the embryo from the uterine tube

• Rupture of the uterine tube and ensuing hemorrhage can be life-threatening

Uterus

• The uterus is a pear-shaped organ with thick, muscular walls. Its largest part, the body, is entered by the left and right uterine tubes and the curved, superior area between the tubes is called the fundus.

• The uterus narrows in the isthmus and ends in a lower cylindrical structure, the cervix. The lumen of the cervix, the cervical canal, has constricted openings at each end: the internal os opens to the main uterine lumen and the external os to the vagina.

• The uterine wall has three major layers:

• Endometrium: Mucosa lined by simple columnar epithelium.

• Myometrium: A thick tunic of highly vascularized smooth muscle

• Perimentrium: An outer connective tissue layer continuous with the ligaments, which is adventitial in some areas, but largely a serosa covered by mesothelium

Endometrium

• The stroma of the endometrium contains primarily nonbundled type III collagen fibers with abundant fibroblasts and ground substance.

• Simple columnar epithelial lining has both ciliated and secretory cells

• Undergoes cyclic changes during the menstrual cycle.• Basal layer:

• Remains throughout cycle

• Supplied by straight arteries

• Functional layer• Spiral arteries

• The rapid decline in the level of progesterone following regression causes constriction of the spiral arteries and other changes that quickly lead to local ischemia in the functional layer and its separation from the basal layer during menstruation.

• Sloughed off during menstruation

A,d: Proliferative

B,e: Secretory

C,f: Premenstrual

Granulosa lutein cells of the corpus

luteum produce progesterone under the

influence of hCG. Progesterone maintains

the endometrium during pregnancy, and if

progesterone levels are reduced early in

pregnancy, the endometrium will slough

off resulting in a miscarriage.

Proliferative Phase

• Coincides with the follicular phase in the ovary.

• During most of the proliferative phase, the functional layer is still

relatively thin, the stroma is more cellular, and the glands are

relatively straight, narrow, and empty.

• Cells in the basal ends of glands proliferate, migrate, and form the

new epithelial covering over the surface exposed during

menstruation.

• Mitotic figures can be found among both the epithelial cells and

fibroblasts.

Secretory Phase

• After ovulation, the secretory or luteal phase starts as a result of the progesterone secreted by the corpus luteum

• In the secretory phase, the functional layer is less heavily cellular and perhaps four times thicker than the basal layer.

• Progesterone stimulates epithelial cells of the uterine glands that formed during the proliferative phase and these cells begin to secrete and accumulate glycogen, dilating the glandular lumens and causing the glands to become coiled.

• The major nutrient source for the embryo before and during implantation is the uterine secretion.

• Superficially in the functional layer, lacunae are widespread and filled with blood.

Menstrual Phase

• When fertilization of the oocyte and embryonic implantation do not occur, the corpus luteum regresses and circulating levels of progesterone and estrogens begin to decrease 8 to 10 days after ovulation, causing the onset of menstruation.

• The drop-off in progesterone produces (1) spasms of muscle contraction in the small spiral arteries of the functional layer, interrupting normal blood flow, and (2) increased synthesis by arterial cells of prostaglandins, which produce strong vasoconstriction and local hypoxia.

• The basal layer of the endometrium, not dependent on the progesterone-sensitive spiral arteries, is unaffected.

• However, major portions of the functional layer, including the surface epithelium, most of each gland, the stroma and blood-filled lacunae, detach from the endometrium and slough away as the menstrual flow or menses.

Cervix

• Mucosa

• Mucus secreting, highly folded, simple columnar epithelium lines the endocervical canal

• Abrupt change to stratified squamous epithelium of the ectocervix, which projects into the vagina

• Not shed during menstruation

• Lamina propria is a dense collagenous tissue under the epithelium

• Many large branching glands

• Muscularis

• Much less smooth muscle than the rest of the uterus

• To facilitate the passage of spermatozoa, cervical mucus at mid-cycle is less viscous, well-hydrated, and alkaline.

Transformation Zone

• The cervical region around the external os projects slightly into the

upper vagina and is covered by the exocervical mucosa with

nonkeratinized stratified squamous epithelium continuous with that of

the vagina.

• The junction between this squamous epithelium and the mucus-

secreting columnar epithelium of the endocervix occurs in the

transformation zone, an area just outside the external os that shifts

slightly with the cyclical changes in uterine size.

• Periodic exposure of the squamous-columnar junction to the vaginal

environment can stimulate reprogramming of squamous cells which

occasionally leads to intraepithelial neoplasia at that site.

Vagina

• Mucosa

• Epithelium: Stratified squamous (nonkeratinized)

• Lamina propria

• No glands

• Muscularis

• Smooth Muscle

• Serosa

• Connective Tissue rich in elastic fibers

• Glycogen increases in response to estrogen

• Bacterial metabolism of glycogen to lactic acid produces normally acidic luminal pH

• The mucosa normally contains lymphocytes and neutrophils in

relatively large quantities.

Vagina

Breast and Mammary Glands

• In the mammary glands, alveolar secretory units develop after puberty on a branching duct system with lactiferous sinuses converging at the nipple.

• Each mammary gland consists of 15-25 lobes of the compound tubuloalveolartype whose function is to secrete nutritive milk for newborns.

• Each lobe, separated from the others by dense connective tissue with much adipose tissue, is a separate gland with its own excretory lactiferous duct

• Lactiferous sinuses are lined with stratified cuboidal epithelium, and the lining of the lactiferous ducts and terminal ducts is simple cuboidal epithelium covered by closely packed myoepithelial cells.

• Myoepithelial cells lie between basal lamina and glandular cells

• Secretion in the mammary gland is both merocrine (proteins) and apocrine (lipids)

Alveolar Development

Changes in Mammary Glands

• (1) Before pregnancy, the gland is inactive, with small ducts and only

a few small secretory alveoli.

• (2) Alveoli develop and begin to grow early in a pregnancy.

• (3) By midpregnancy, the alveoli and ducts have become large and

have dilated lumens.

• (4) At parturition and during the time of lactation, the alveoli are

greatly dilated and maximally active in production of milk components.

• (5) After weaning, the alveoli and ducts regress with apoptotic cell

death.

Oxytocin involved in the suckling reflex.

Stimulation of nerves in the nipple by

suckling is transmitted to hypothalamus,

resulting in release of oxytocin from axon

terminals located in posterior pituitary,

which promotes contraction of

myoepithelial cells leading to milk ejection

(milk let down)

Fibrocystic:

• Proliferation of the connective

tissue stroma and cystic

formation of ducts (fluid filled)

• Results from increasing

hormone levels.

• Painful (mastalgia)

Fibroadenoma:

• Slow-growing mass of

epithelial and connective

tissues (solid mass)

• Painless

Benign Breast Disorders

Breast Cancer

• Most common malignancy in women

• Breast tumors arise in ductal

epithelium (90% of cases) or within the

lobular alveolar epithelium (10% of the

cases)

• If the tumor is confined within the duct

or lobule in which it arose, then it is

referred to as carcinoma in situ or

noninfiltrating.

• If the tumor has broken through the

duct or lobule crossing the basement

membrane of the epithelium, then it is

referred to as invasive carcinoma.

MALE HISTOLOGY

Functions of the Male Reproductive Tract

• The male reproductive system consists of the testes, genital ducts, accessory glands, and penis

• Spermatogenesis (formation of spermatozoa in the testes)

• Maturation and Storage of Spermatozoa (epididymis)

• Delivery of Mature Sperm to the Female Reproductive Tract

• Endocrine Organ (Testosterone)

• Clinical Issues with the Male Reproductive Tract• Cryptorchidism

• Infertility

• Erectile Dysfunction/Ejaculatory Problems

• Prostatic Disease [Infection, Benign Prostatic Hypertrophy (BPH), Cancer]

• Testicular Cancer (disease of young men)

Testes

• Each testis (or testicle) is surrounded by a dense connective tissue capsule, the tunica albuginea

• Septa penetrate the organ and divide it into about 250 pyramidal compartments or testicular lobules

• Each lobule contains sparse connective tissue with endocrine interstitial cells (or Leydig cells) secreting testosterone, and one to four highly convoluted seminiferous tubules in which sperm production occurs.

• Each tubule is a loop attached by means of a short straight tubule to the rete testis (RT), a maze of channels embedded in the mediastinum testis.

• From the rete testis the sperm move via 15 or 20 efferent ductules into the epididymis

Leydig Cells

• Located in interstitial tissue near blood vessels

• Synthesis of androgens (testosterone) in response to LH

• Concentration of testosterone in seminiferous tubules is higher than in

the blood

• Contain lipid droplets, smooth ER and many mitochondria

Seminiferous Tubules

• Mucosa

• Complex, specialized stratified epithelium called germinal epithelium

• Large nondividing Sertoli cells

• Dividing cells of the spermatogenic lineage

• BM: Covered by fibrous connective tissue, with an innermost layer containing

flattened, smooth muscle-like myoid cells which allow weak contractions of the

tubule.

• Surrounded by interstitial tissue and Leydig Cells

Sertoli cells: Functions

• Mediate the effects of FSH and testosterone on regulation of spermatogenesis

• Create a microenvironment that promotes meiosis and spermiogenesis

• Physical support & nutrition of germ cells

• Release of late spermatids to lumen (spermiation)

• Phagocytosis of cytoplasmic droplets from spermatids

• Secretion - fluid and proteins, including androgen-binding protein (ABP), inhibin, activin, transferrin, anti-Mullerian hormone.

• Formation of blood-testis barrier (tight junctions)

• Don’t divide in adults – resistent to radiation and chemotherapy

The primary spermatocytes remain for 3

weeks in prophase of the first meiotic

division during which recombination

occurs.

Secondary spermatocytes are rarely seen

because they undergo the second meiotic

division almost immediately to form two

haploid spermatids.

Spermiogenesis

A spermatid undergoes spermiogenesis

by greatly condensing its nucleus, forming

a long flagellum with a surrounding

mitochondrial middle piece, and forming a

perinuclear acrosomal cap.

Rete Testis

• The flattened

anastomosing lumens

of the rete testis are

lined by a flattened

simple epithelium

• Mucosa: Simple

squamous to simple

cuboidal epithelium

Efferent Ducts

• Multiple tubules that connect rete testis

to epididymis.

• Absorb most of the fluid produced in the

seminiferous tubules.

• Mucosa:

• Nonciliated cuboidal cells alternate with groups

of taller ciliated cells and give the tissue a

characteristic scalloped or ragged appearance

• Only place with motile ciliated cells in

male reproductive tract!!

Epididymis

• The long, coiled duct of the epididymis, surrounded by connective tissue, lies in the scrotum.

• While passing through this duct, sperm become motile and their surfaces and acrosomes undergo final maturation steps. Glycolipid decapacitation factors bind sperm cell membranes and block acrosomal reactions and fertilizing ability.

• Mucosa• Pseudostratified columnar epithelium

• Columnar principal cells, with characteristic long stereocilia, and small round stem cells.

• Principal cells secrete glycolipids and glycoproteins and absorb water and remove residual bodies or other debris not removed earlier by Sertoli cells.

• Muscularis: The duct epithelium is surrounded by a few layers of smooth muscle cells, arranged as inner and outer longitudinal layers as well as a circular layer in the tail of the epididymis.

Epididymis

Epididymis vs. Efferent Duct

Epididymis

Efferent

duct

(even)

(uneven)

stereocil

ia

The epididymis promotes sperm

maturation by secretion of materials into

and absorption of materials out of the

epididymal lumen.

The stereocilia provide increased surface

area for the apical surface of the

epididymal epithelial cells facilitating

secretion and absorption

Transit time is 10 - 12 days

Vas Deferens

• Long straight tube with a thick, muscular wall and a relatively small lumen

• Mucosa • Folded longitudinally

• Epithelial lining is pseudostratified with sparse stereocilia

• Lamina propria contains many elastic fibers

• Muscularis• The very thick muscularis consists of longitudinal inner and outer layers and a

middle circular layer.

• The muscles produce strong peristaltic contractions during ejaculation, which rapidly move sperm along this duct from the epididymis.

• Passes over the urinary bladder where it enlarges as an ampulla. Within the prostate gland, the ends of the two ampullae merge with the ducts of the two seminal vesicles, joining these ducts to form the ejaculatory ducts which open into the prostatic urethra.

Accessory Glands

• Three sets of glands connect to the ductus deferens or urethra:

• Paired seminal vesicles

• Large saccular glands, highly folded mucosa surrounded by SM, secretions rich in

protein and fructose

• Prostate

• Multiple small glands, varied epithelium, glands are tortuous often leading to infection,

corpora amylacea

• Paired bulbourethral glands

• Lubricates in preparation for ejaculation, mucus-secreting simple columnar epithelium

that is also testosterone-dependent

• The first two types of glands contribute the major volume to semen

and the latter produces a secretion that lubricates the urethra before

ejaculation.

The many small twisted glandular units do

not empty efficiently during contraction of

the smooth muscle in the stroma of the

prostate during ejaculation. This helps

bacteria establish and maintain

themselves hence the problem with

prostatic infections (prostatitis) and the

difficulty in getting rid of them.

Penis

• The penis consists of three cylindrical masses of erectile tissue, plus the penile urethra, surrounded by skin • Two of the erectile masses—the corpora cavernosa—are dorsal

• The ventral corpus spongiosum surrounds the urethra.

• At its end the corpus spongiosum expands, forming the glans.

• Most of the penile urethra is lined with pseudostratified columnar epithelium.

• In the glans, it becomes stratified squamous epithelium

• Small mucus-secreting urethral glands are found along the length of the penile urethra.

• In uncircumcised men the glans is covered by the prepuce or foreskin

Erection

• For erection parasympathetic stimulation relaxes muscle of the small

helicine arteries and adjacent tissues, allowing vessels of the

cavernous tissue to fill with blood; the enlarging corpora compress the

venous drainage, producing further enlargement and turgidity in the

three corpora masses.

• The sympathetic stimulation at ejaculation constricts blood flow

through the helicine arteries, allowing blood to empty from the

cavernous tissues.

• Nitric oxide released by nerves increases cGMP and promotes

relaxation of the arteries

ANATOMY

Lymph Drainage of the Breast

• All breast lymph initially drains into the deep subareolar plexus.

• It gets there by moving between several interconnected plexuses

within the breast, including the circumareolar, perilobular, and

interlobular.

• Medial quadrant:

• Parasternal Lymph nodes Bronchomediastinal nodes

• Lateral quadrant:

• Pectoral Lymph nodes or Axillary lymph nodes Infra and

Supraclavicular nodes

Pelvic Structures

• Females• Shape of pelvic inlet

• Oval shaped

• Size of pelvic outlet• Comparatively larger (Everted ischial tuberosities)

• Shape of pelvic outlet• Diamond shaped

• Subpubic angle• Wide: 90 degrees

• Males• Shape of pelvic inlet

• Heart-shaped

• Size of pelvic outlet• Comparatively small

• Shape of pelvic outlet• Diamond shaped

• Subpubic angle• Narrow: 70 degrees

Pelvic Diameter

• True conjugate pelvis diameter:

• Distance from sacral promontory to superior margin of pubic

symphysis. Measured radiographically

• Diagonal conjugate pelvis diameter:

• Distance from sacral promontory to inferior margin of the pubic

symphysis

• Pelvic outlet measurements

• Transverse diameter: Distance between ischial tuberosities

• Interspinous diameter: distance between ischial spines.

• This diameter is the smallest and can be a physical barrier to childbirth

• <9.5cm

Neural Structures at Risk

• Birth

• Both the mother’s sacral plexus and obturator nerve are at risk of

compression during childbirth. This leads to pain in the lower limbs.

• Surgery

• During surgery, particularly with removal of cancerous lymph nodes

along the iliac artery, the obturator nerve is at risk.

• The obturator nerve supplies the medial compartment of the thigh.

Muscular and Tissue Trauma of Childbirth

• Cystocele

• Fibrous wall between the bladder and vagina walls overstretches

and tears, the bladder can herniate into the vagina.

• Rectocele

• Fibrous septum between the rectum and vagina tears during

childbirth, allowing rectal herniation into the vagina

• Uterine prolapse

• Tearing of several muscles and ligaments meant to hold the uterus

in place, allowing prolapse into the vaginal area. The most

important ligaments are the uterosacral.

Pelvic Pain

• The peritoneum determines the

pathway of referred pain from pelvic

viscera.

• Pain from regions in contact with the

peritoneum travels via sympathetic

pathways to the L1-L3 spinal cord.

• Pain from those regions of the uterus not

covered in peritoneum, as well as the

remainder of the pelvic portion of the birth

canal, travels via parasympathetic

pathways back to the S2-S4 spinal cord.

• Pain from the perineal portion of the birth

canal is somatic and travels in the pudendal

nerve (derived from S2-S4 ventral rami)

Spinal Block and Epidural Block

• Spinal block:• Anesthetic is injected directly into the subarachnoid space at L3/L4.

Anesthetizes all spinal nerves below the level of T9.

• Mother cannot feel the uterine contractions and motor and sensory functions of the lower limbs are temporarily lost.

• Caudal epidural block:• Anesthetic is administered into epidural space of the sacral canal,

restricting the effect to the sacral spinal nerves.

• Entire birth canal, pelvic floor and most of the perineum (the anterior portions of the peritoneum are innervated by the ilioinguinal and genitofemoral nerves) are anesthetized.

• The mother is aware of her contractions and lower limb function is maintained.

Spinal Block

Epidural Block

Pudendal Nerve Block

• Procedure

• Anesthesia (1% lidocaine) is injected transvaginally or lateral to the

labia majora around the tip of the ischial spine and through the

sacrospinous ligament.

• Effects

• Perineal anesthesia during forceps childbirth delivery by

anesthetizing the pudendal nerve to obtain a full anesthesia of the

perineal region.

• Also anesthetize the ilioinguinal nerve, genitofemoral nerve, and

perineal branch of the posterior femoral cutaneous nerve

Position of the Uterus

• Uterus is normally in an ANTEFLEXED and

ANTEVERTED position

• places the uterus in a nearly horizontal position lying on

the superior wall of the urinary bladder

• Anteflexed: anterior bend of the uterus at the angle between the

cervix and the body of the uterus

• Anteverted: refers to the anterior bend of the uterus at the angle

between the cervix and the vagina

• If on bladder - anteverted

• If on rectum - retroverted

Ectopic Pregnancy

• Most often occurs in the ampulla of the uterine tube

• Risk factors• Salpingitis

• Pelvic Inflammatory Disease

• Pelvic surgery

• Exposure to diethylstilbestrol (DES)

• General theme: scarring raises of probability of ectopic pregnancies.

• Symptoms• Sudden onset of abdominal pain

• Last menses 60 days ago

• Positive hCG test

• Culdocentesis (culdo-from rectouterine pouch) showing intraperitoneal blood

• If hemodynamically compromised - take to OR immediately - this is an emergency as it indicates a peritoneal bleed from a ruptured ectopic pregnancy

The ureter is at risk of injury in a

hysterectomy, and can be damaged

where it crosses the uterine arteries.

Posterior Vaginal Fornix

• Posterior Vaginal Fornix - located posterior to the cervix and is related

to the RECTOUTERINE POUCH

• The rectum, sacral promontory (S1 vertebral body) and coccyx are

palpable through the posterior fornix during digital/penile examination

• Posterior fornix is the site for culdocentesis (collecting fluid from the

POUCH OF DOUGLAS)

Lymph Drainage of Pelvis

• Body of the uterus: External iliac and Lumbar nodes.

• Rest of the uterus: Obturator, internal iliac and external iliac arteries

• Cervix: External and internal iliac nodes

• Ovaries: Lumbar nodes

• Pudendum: Superficial inguinal

• Testes: Lumbar lymph nodes

• Scrotum: Superficial inguinal lymph nodes

• Ovary, Uterine Tubes, Uterine Fundus - lumbar lymph nodes

• Uterus region near round ligament attachment - superficial inguinal lymph nodes

Vaginal and Bimanual Exams

• Structures Palpated

• Clitoris, prepuce (clitoral hood), labia majora/minora. vagina (walls),

cervix (external os), uterus, ovaries, Fallopian tubes/ovarian ducts,

rectum, rectovaginal septum

Bartholin Cyst

• Bartholin Cyst - caused by an obstruction of the duct from the greater vestibular glands of bartholin

• Bartholin Gland located on each side of the vaginal opening. These glands secrete fluid that helps lubricate the vagina.

• Openings of these glands can become obstructed, causing fluid to back up into the gland, causing a relatively painless swelling (cyst).

• The fluid in the cyst can become infected, resulting in pus surrounded by inflamed tissue (abscess)

Digital Rectal Exam

• Structures Palpated

• Tone of the external anal sphincter

• Rectal walls are examined for irregularities

• Anteriorly, the prostate gland and seminal vesicles are palpated

• CA of the prostate typically develops in the posterolateral region

which can be palpated in the digital rectal exam

• Malignant prostate feels hard, irregular

• Additional Structures: ischioanal fossa, ischial spine, sacrum,

coccyx

Pain from the seminal vesicles and

prostate travels via the pelvic splanchnic

nerves and is referred to the S2-S4

dermatomes.

Prostate

• Three Zones• Central zone surrounds the ejaculatory ducts

• Transition zone surrounds proximal urethra

• Peripheral zone surrounds distal urethra and makes up the bulk of the glandular tissue

• Five Lobes• Median: Between posterior to urethra, anterior to ejaculatory ducts

• Posterior: Posterior to ejaculatory duct

• Lateral (Left and Right): Lateral to the median and posterior lobes

• Anterior: Anterior to urethra, only fibromuscular, no glands

• BPH usually occurs as hyperplasia of the transition zone, corresponding to portions of the middle and lateral lobes that surround the urethra

• Prostatic carcinoma is most commonly found in the peripheral zone involving the posterior lobe

Venous Drainage of the Prostate

• First pathway: Prostatic venous plexus → Internal iliac veins →

inferior vena cava (IVC). This may explain the metastasis of prostatic

cancer to the heart and lungs.

• Second pathway: Prostatic venous plexus → vertebral venous plexus

→ cranial dural sinuses. This may explain the metastasis of prostatic

cancer to the vertebral column and brain.

Metastases Overview

• Prostate cancers hematogenously spread

• 1. Internal iliac inferior vena cava heart and lung metastases

• 2. Vertebral venous plexus cranial dural sinuses brain and

vertebral column metastases

• Scrotal cancers spread to the superficial inguinal nodes

deep inguinal external iliac

• Testicular cancers spread to the deep lumbar nodes

Path of Sperm

• Sperm moves from the epididymis to the ductus deferens:• The ductus deferens begins at the inferior pole of the testes ascends to enter the

spermatic cord (SNIP AROUND HERE)

• Transits the inguinal canal

• Enters the abdominal cavity by passing through the deep inguinal ring

• Crosses the external iliac artery and vein

• Enters the pelvis

• Vasectomy

• The scalpel will cut through the following layers in succession to gain access to the ductus deferens.

• Skin colles fascia and dartos muscle external spermatic fascia cremasteric fascia and muscle internal spermatic fascia extraperitoneal fat. (The tunica vaginalis is not cut)

• Through incisions at the apex of the scrotum, the ductus deferens is cut bilaterally in the spermatic cord to prevent sperm from passing into the urethra.

Varicocele

• Varicocele is an abnormal dilatation of the pampiniform plexus and testicular vein

• Pampiniform plexus is an extensive network of veins that surround the testicular artery within the spermatic cord. It serves as a counter-current heat exchanger for blood flowing to and from the testes.

• Presents as a palpable “bag of worms” scrotal swelling.

• Most often on the left side (90%) due to compression of the left testicular vein by the sigmoid colon

• Nutcracker Syndrome (SMA compressing L renal v.)

• L-sided Renal Cell Carcinoma which has invaded L renal v.

• Often associated with infertility.

Cancer of the Testes and Scrotum

• Cancer of the scrotum will metastasize to the superficial

inguinal nodes.

• Scrotum drains to the superficial inguinal nodes → deep inguinal

nodes → external iliac nodes → common iliac nodes → abdominal

confluence → thoracic duct.

• Cancer of the testes will metastasize to deep lumbar nodes

due to the embryologic development of the testes within the

abdominal cavity and subsequent descent into the scrotum.

• May involve retroperitoneal lymph nodes (regional lymph node

involvement), and then can spread to pelvic, chest, and

supraclavicular lymph nodes (distant lymph node involvement)

Erection

• Erection

• Parasympathetic initiates - pelvic splanchnic nerves (S2 - S4) engorge corpora cavernosa and corpus spongiosum mm

• Somatic maintains - perineal branch of pudendal nerve contracts bulbospongiosus and ischiocavernosus mm

• Emission

• Sympathetic - hypogastric nerve contracts smooth muscle (epididymis, ductus deferens, seminal vesicle, prostate) to move sperm forwards and prevent reflux of sperm backwards (internal urethral sphincter)

• Ejaculation

• Somatic - pudendal nerve contracts bulbospongiosus m and relaxes the sphincter urethrae m

Impotence and Prostatectomy

• The common basis for erectile dysfunction following radical

prostatectomy is the severing of the cavernous nerves, which

mediate autonomic neuroregulatory function and course along the

lateral aspects of the prostate and rectum.

• The cavernous nerve travels from the pelvic plexus proximally to the

penis distally, in close anatomical relationship to the seminal vesicle,

prostate, striated urethral sphincter, bladder, and rectum.

Hydrocele vs. Varicocele

• Hydrocele

• Increase in fluid due to incomplete obliteration of the processus vaginalis.

• Occurs when a small patency of the processus vaginalis remains so that the

peritoneal fluid can flow into the tunica vaginalis surrounding the testes.

• Can be secondary to infection or to lymphatic blockage by tumor.

• Diagnosis: transillumination and US

Varicocele

Cryptorchidism

• Undescended testes (one or both).• Occurs when the testes begin to descend along the normal pathway but fail to

reach the scrotum.

• This is different from an ectopic testes (see below) which occurs when the testes descend along an abnormal pathway.

• Undescended testis is generally found within the inguinal canal or abdominal cavity near the deep inguinal ring.

• Consequences: impaired spermatogenesis (because sperm develop best at temperatures < 37 deg C); normal testosterone levels (as Leydig cells are unaffected by temperature);

• Associated with an increased risk of germ cell tumors.

Ectopic Testes

• A testicle that has taken a non-standard descent through the body

and ended up in an abnormal location.

• Testes descend normally through the external ring but are then

diverted to an aberrant position.

• May be palpable in the superficial inguinal pouch (most common),

suprapubic region, femoral canal, perineum, or contralateral scrotal

compartment (least common)

Testicular Torsion

• The rotation of the testes about the spermatic cord, usually towards

the penis (ie, medial rotation).

• Increased incidence occurs in men with testes in a horizontal position

and a high attachment of the tunica vaginalis to the spermatic cord

(“bell clapper deformity”)

• Torsion is a medical emergency because compression of the

testicular vessels results in ischemic necrosis within 6 hours.

Inguinal Ligament and Canal

• The inguinal ligament extends from the ASIS (anterior superior iliac spine) of the ilium to the pubic tubercle of the pubis bone.

• It is formed by the inferior free edge of the aponeurosis of the external oblique muscle.

• In men, the spermatic cord, the testes and its associated lymphatics, vessels and ducts are the main occupants while in women it is mainly the round ligament of the uterus.

• The superficial inguinal ring seems to be composed of the aponeurosis of the external oblique muscle

• The deep inguinal ring is created from the innermost layer, the transversalis fascia.

Layers of the Spermatic Fascia

• The three layers of the spermatic fascia are created by the three layers of the abdominal wall at this portion of the abdomen.

• Remember that the aponeurosis of the transverse abdominis stops midway between the umbilicus and the pubic crest creating the arcuate line.

• So where the spermatic fascia begins, the three layers, superficial to deep, are:• Aponeurosis of external oblique external spermatic fascia

• Aponeurosis of internal oblique cremasteric fascia

• Transversalis fascia internal spermatic fascia

Processus Vaginalis

• In development, the processus vaginalis is a diverticulum of the peritoneal cavity.

• It elongates downward during the 8th week of development with the gubernaculum (ligamentous cord attached to the gonads).

• The processus vaginalis pushes the anterior abdominal wall layers in front of its path, which in order from deep to superficial are: transversalis fascia (TF), aponeurosis of internal oblique (IO), aponeurosis of external oblique (EO).

• This path it has created is the inguinal canal.

• The processus vaginalis’s fate is that the proximal portion will degenerate but the distal portion will persist as the tunica vaginalis

Hernias

• Direct inguinal hernias: older men, goes through

superficial inguinal ring (does not enter scrotal fascias),

weakness in abdominal wall, medial to inferior epigastric

artery.

• Indirect inguinal hernias: younger men, goes through

deep and superficial inguinal rings (and can enter

scrotum), lateral to inferior epigastric artery.

• Femoral hernias: women, goes through subinguinal

space into femoral canal.

Surgical hernia repair may damage the:

Iliohypogastric nerve, causing anesthesia

of the ipsilateral (same side) abdominal

wall and inguinal region.

Ilioinguinal nerve, causing anesthesia of

the ipsilateral penis, scrotum, and medial

thigh.

Cremasteric Reflex

• Afferent limb: ilioinguinal n. and femoral branch of the genitofemoral

n. supplying the skin of the upper thigh

• Elicited: brushing skin of upper medial thigh

• Efferent limb: the genital branch of the genitofemoral n.

• The genital branch of the genitofemoral enters and passes through

the inguinal canal and in males it supplies the cremaster muscle

(derived from the internal oblique muscle of the abdomen) of the

spermatic cord.

• In a normal cremaster reflex brushing the skin in the superior aspect

of the upper thigh causes the cremaster to contract, thus elevating the

scrotum.

Indifferent Gonads

• Medulla: • Inner portion of the genital ridge (intermediate mesoderm)

• Males keep the medulla

• Cortex (Primitive Sex Cords): • Outer portion of the genital ridge (coelomic epithelium)

• Females keep the cortex

• Primordial germ cells: (epiblast)• Cells migrate into the yolk sac during gastrulation to avoid the differentiation of

tissues that occurs within the gastrulating embryo.

• After gastrulation these cells migrate back through the vitelline duct and primitive gut tube to populate the primitive gonads

• Ovarian teratomas and dermoid cysts:• Benign cystic tumors of the ovary

• Derived from the totipotent primordial germ cells in primitive gonads

• Can contain recognizable structures such as hair, bone and sebaceous material

Uterine Anomalies

• Class I( (mullerian agenesis): Uterus does not develop

• Class II (unicornuate uterus): A mullerian horn fails to develop fully

resulting in a one horned uterus

• Class III (uterine didelphys): Müllerian ducts incompletely fuse at the

fundus leading to 1 cervix, 1 vagina but 2 endometrial cavities

• Class V (septate uterus): Most common. The septum between the

two mullerian ducts fails to compleetly resorb resulting in a divided

uterus

• Imperforate hymen: hymen that has not perforated so that fluids can

escape.

Gender can be identified by the 12th or

13th week.

Androgen Effects

• Testosterone-

• Tells mesonephric duct and tubules to form efferent ductules, epididymis, ductus

deferens and ejaculatory duct

• Dihydrotestosterone-

• Elongates genital tubercle to form the penis

• Enlarges the labiosacral (genital) swellings to form the scrotum

Lack of Androgen Effects

• Androgen insensitivity syndrome- Absence of androgen receptors or

failure to respond

• Males develop female genitalia and secondary sex characteristics

• Testes are present in inguinal or labial region and produce hormones

• Anti-mullerian substance suppresses development of uterus and tubes

• No response to testosterone so no internal genital organs

• Male pseudohermaphroditism- reduced production of androgens and

anti-mullerian substance

• Internal and external genitalia are incompletely differentiated

Hypospadia & Epispadia

• Hypospadia- urethral folds

don’t completely fuse

• Epispadia- faulty positioning

of genital tubercle

• Non-fusion on top of penis

• Bladder is often exposed.

Female External Genitalia Development

• No DHT so genital tubercle bends inferiorly to form clitoris

• Urogenital groove stays open and forms vestibule

• Genital swellings labia majora

• Urethral folds labia minora

• Congenital adrenal hyperplasia- adrenal gland secretes excess

androgens masculinizing the female genitalia

Sex Chromosome Quantity Syndromes

Turner’s Syndrome

• Karyotype XO (female)

• Presents with:

• Streaked gonads (infertile)

• Short stature

• High arched palate

• Webbed neck

• Shield-like chest

• Inverted nipples

• Cardiac and renal problems

Klinefelter’s Syndrome

• Most common

abnormality of sexual

differentiation

• Karyotype XXY (male)

• Presents with

• Infertility

• Gynecomastia

• Impaired sexual maturation

• Underandrogenization

DEVELOPMENT

Week 3: Gastrulation

• Germ cells escape to yolk sac to avoid differentiation.

They are derived from the epiblast of the embryo

QuickTime™ and a decompressor

are needed to see this picture.

NOTE: These are totipotent cells.

Source of ovarian teratomas &

dermoid cysts

Week 4: Genital RidgeMedulla=

Intermediate mesoderm

Cortex=

Coelemic epithelium

End of Week 4: Return of the Germ Cells

• Epithelial cells make primitive sex cords (home for germ cells)

• Germ Cells return thru vitelline duct

Week 5: It All Comes Together

Differentiation of the Indifferent Gonad

• The SRY gene is located on the short arm of the Y chromosome, near

the region of homology with the X chromosome is responsible for

differentation of the indifferent gonad

• By virtue of this location, the SRY gene is susceptible to I

translocation to the X chromosome, leading to XX male syndrome.

• These individuals are characterized by male genitalia and testes, but no sperm

production.

• Males: Testis Determining Factor, encoded by the SRY gene

• Gonads will develop into testis

• Females: Do NOT have Testis Determining Factor

• Gonads will develop into ovaries

Male Development

• SRY gene (short arm of Y chromosome or translocated to X in XX male syndrome)

• Primitive sex cords medullary testis cords sertoli cells seminiferous tubules, rete testis

• Tunica albugenia forms

• Cortex degenerates

• Mesenchyme Leydig cells

Week 8: Males

• Leydig cells Testosterone

• Sertoli Cells antimullerian substance

Females

• No SRY

• Medulla/primitive sex cords

degenerate

• BUILD cortical cords, invest

germ cells follicle cells of

ovary

Mesonephric vs Paramesonephric duct

Girls build new

(paramesonephric duct)Boys use what’s there

(mesonephric duct)

Males

Mesonephric Duct

• Efferent ductules- epididymis

• Ductus deferens

• Seminal vessicle

• Ejaculatory duct

Paramesonephric

• Remnants

• Prostatic utricle

• Appendix testis

• Rest is degenerated

• Antimullerian

Female Duct Development

• Paramesonephric duct persists, makes:• Uterus, uterine tubes, and upper 4/5

of vagina

• Mesonephric duct degenerates:• Remnants:

• Gartner’s cyst

• Paraovarian and parafallopian cysts

Paramesonephric Vs Urogenital Sinus

• Urogenital Sinus

• forms the neck of the bladder, urethra and vestibule

• Paramesonephric

• forms upper 4/5 of vagina, uterus and the fallopian tubes

• Basically the sinus does the outside structures and the paramesonephric does the internal ones.

Gonadal Dysgenesis

• Gonadal dysgenesis:• Unlike testes, the presence of viable germ cells is ESSENTIAL for

ovarian differentiation

• If primordial germ cells fail to reach the genital ridges, are abnormal, or degenerate, the gonad regresses (gonadal dysgenesis) and streak ovaries result.

• People with gonadal dysgenesis are phenotypically female, but may have a variety of chromosomal complements

• XY gonadal dysgenesis (Swyer syndrome): SRY point mutation• Appear to be normal females

• Do not menstruate or develop secondary sex characteristics

• Turner syndrome: XO chromosome complement • Short stature, high and arched palate, webbed neck, shield-like chest,

inverted nipples, cardiac and renal abnormalities (coarctations & horseshoe kidneys)