Review

1. ENDOCRINE
REPRODUCTIVE
HISTOLOGY

2. FEMALE HISTOLOGY

3. 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.

5. 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.

7. Primordial follicles are the only follicles
present at birth.

8. 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.

9. The zona pellucida is complete in the
multilaminar follicle and contains
glycoproteins ZP3 and ZP4 that are
critical for fertilization.

10. 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.

11. Atresia

12. 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

13. 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)

14. 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

15. 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

18. 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.

19. Corpus Luteum

20. 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

21. Corpus Albicans

22. 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.

23. 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

25. Mucosa of Uterine Wall

26. 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.

27. 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  blastomeres
become 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.

29. Women with immotile cilia syndrome are
still fertile, presumably because of the
smooth muscle serving as a backup
system.

31. 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 stroma
components, 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.

32. 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.

33. Placenta

35. The placenta is also an endocrine organ
roducing HCG, a lactogen, relaxin, and
various growth factors, in addition to
estrogen and progesterone.

36. 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
Placenta
Cytotrophoblast

37. 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

38. 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

40. 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

41. 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

42. A,d: Proliferative
B,e: Secretory
C,f: Premenstrual

43. 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.

44. 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.

45. 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.

46. 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.

47. 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.

50. 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.

51. 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.

52. Vagina

53. 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 tubuloalveolar
type 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)

54. Alveolar Development

55. 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.

56. 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)

57. Benign Breast Disorders
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

58. 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.

59. MALE HISTOLOGY

60. 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)

62. 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

64. 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

65. 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

68. 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

69. 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.

70. Spermiogenesis

71. 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.

72. Rete Testis
• The flattened
anastomosing lumens
of the rete testis are
lined by a flattened
simple epithelium
• Mucosa: Simple
squamous to simple
cuboidal epithelium

73. 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!!

74. 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.

76. Epididymis

77. Epididymis vs. Efferent Duct
Epididymis
Efferent
duct
(even)
(uneven)
stereocil
ia

78. 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

79. Transit time is 10 - 12 days

80. 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.

83. 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.

84. 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.

85. 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

88. 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

89. ANATOMY

90. 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

92. 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

94. 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

95. 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.

96. 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.

98. 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)

99. 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.

100. Spinal Block
Epidural Block

101. 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

103. 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

105. 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

107. The ureter is at risk of injury in a
hysterectomy, and can be damaged
where it crosses the uterine arteries.

108. 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)

109. 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

111. 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

112. 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)

113. 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

115. Pain from the seminal vesicles and
prostate travels via the pelvic splanchnic
nerves and is referred to the S2-S4
dermatomes.

116. 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

118. 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.

119. 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

120. 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.

122. 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.

124. 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)

125. 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

126. 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.

128. 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

129. Varicocele

130. 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.

131. 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)

133. 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.

135. 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.

138. 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

139. 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

140. 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.

142. 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.

143. 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.

145. 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

146. 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.

148. Gender can be identified by the 12th or
13th week.

149. 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

150. 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

151. 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.

152. 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

154. 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

155. DEVELOPMENT

156. Week 3: Gastrulation
• Germ cells escape to yolk sac to avoid differentiation.
They are derived from the epiblast of the embryo
NOTE: These are totipotent cells.
Source of ovarian teratomas &
dermoid cysts
Quic kTime™ and a
decompressor
are needed to see this picture.

157. Week 4: Genital Ridge
Medulla=
Intermediate mesoderm
Cortex=
Coelemic epithelium

158. 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

159. Week 5: It All Comes Together

160. 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

161. 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

162. Week 8: Males
• Leydig cells  Testosterone
• Sertoli Cells  antimullerian substance

163. Females
• No SRY
• Medulla/primitive sex cords 
degenerate
• BUILD cortical cords, invest
germ cells  follicle cells of
ovary

164. Mesonephric vs Paramesonephric duct
Girls build new
(paramesonephric duct)
Boys use what’s there
(mesonephric duct)

165. Males
Mesonephric Duct
• Efferent ductules- epididymis
• Ductus deferens
• Seminal vessicle
• Ejaculatory duct
Paramesonephric
• Remnants
• Prostatic utricle
• Appendix testis
• Rest is degenerated
• Antimullerian

166. 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

167. 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.

168. 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)