SEXUAL DIFFERENTIATION I
Migration of Primordial Germ Cells
 yolk sac  hind gut  gonadal/genital ridge
SEXUAL DIFFERENTIATION II
Differentiation of the Internal Genital Ducts
Immature Germ Cells
 have 2n chromosomes
o oogonia – 46XX
o spermatogonia – 46 XY
Benign Cystic Teratoma
 when pleuripotent germ cells do not migrate to
the gonadal ridges
Differentiation of the Gonads
XY individual
XX individual
primitive sex chords
primitive sex chords
hollow out
degenerates
seminiferous tubules
cortex develops
forms
(surroundings of medulla)
rate testis develops, key
2o sex chords formed
structure of testis where
where oogonia will reside
spermatogonia will reside
Undifferentiated
Structure
Wolffian Duct
Mellurian Duct
Bipotential Gonads
 +Y choromosome
o primitive sex chords  seminiferous
tubules + rete testis
 -Y chromosome
o Degeneration of 1o sex chords  ovary
Turner’s syndrome
 45, XO (only one X chromosome)
SRY gene (Sex-determining Region Y)
 on Y chromosome
 makes testis determining factor (TDF)
Testis
 at 8-9 wks of fetal dev, makes
o androgens (ex testosterone) fr Leydig
cells
o anti-mellurian hormone fr Sertolli cells
SRY/TDF gene
 at the tip of the short arm of Y chromosome
 translocation occurs at meiosis I and propase I
Sex reversal
 disparity between genotype & phenotype sex
 SRY translocations to the X chromosome leads
to XX male
 SRY deletion results in female with vestigial
streak gonads
Male
Female
+ testosterone
 epididymis
 vas deferens
 seminal vesicles
 ejaculatory duct
– testosterone
 regression
+ AMH
 regression
– AMH
 fimbria
 fallopian tubes
 fundus & corpus
of uterus
 cervix
 upper 1/3 vagina
-
Anti-Mellurian Hormone (AMH)
 or Mellurian inhibiting substance (MIS)
 produced by Setoli cells
 chromosome 19, regulated by SRY gene/TDF
transcription factor
 inhibits mellurian mesenchymal and epithelial
growth to induce apoptosis
Differentiation of the Urogenital Sinus
Undifferentiated
Male
Female
Structure
vesicle
urinary bladder
urinary bladder
pelvic
prostatic portion
entire urethra
of urethra
phallic
initial portion of
vestibule/lower
penile urethra
part of vagina
* development of urorectal septum separates
urogenital & digestive systems
Differentiation of the External Genitalia
Undifferentiate
Male
Female
d Structure
genital tubercle glans penis
clitoris
urethral folds
shaft of penis
labia minora
labiocrotal
swellings
urogenital slit
scrotum
labia majora
urethral miatus
anal indention
anus
urethra &
vaginal opening
anus
Male Tissues Differentiated by Testosterone
 Testis
 Mesonephric tubules  efferent ductules
 Wolffian duct differentiation
 Testicular descent
Male Tissues Differentiated by DHT
 Virilization of urogenital sinus into prostatic &
phallic parts of urethra
 Prostate & bulbourethral glands
 External genitalia
Abnormalities of Sexual Differentiation
Hypospadias
 urogenital folds do not fuse appropriately
 urethral opening underside of penis instead of
at the tip
Cryptorchism
 incomplete testicular descent
Inguinal Hernias
 more in male than female
 70% of hernias are inguinal
MALE REPRODUCTIVE PHYSIOLOGY I
Major Structures of the Male Reproductive Tract
Gonads
Major Testis Structures
 seminiferous tubules
 rete testis
Major Cell Types
 Sertoli
o AMH, ABP, inhibins
 Leydig
o Androgens exp testosterone
 Gamete
Sex Accessories
Spermatogenesis
Seminiferous tubule
Functions of Sertoli Cells





maintenance of blood-testes barrier
nourishment of developing germ cells
production of seminiferous fluid
removal of damaged germ cells
synthesis of ABP and inhibin
Major Organs Involved in Sperm Production,
Maturation and Transport
organs
testes
 sperm production (~10
by vol, 6-10 x 107
sperm/mL semen
epididymis
 sperm transport &
maturation
vas deferens
 sperm storage
seminal vesicles
 seminal fluid production
(nutrients + fructose +
prostaglandins)
~60-70% by vol
prostate
 prostatic fluid pH 6.5
(vagina pH 4) production
Bulbo-urethral gland
 pre-ejaculatory fluid
production
*Epididymal + prostatic + bulbo-urethral fluid ~20-30%
of ejaculate
Hormonal Feedback
cholesterol (27C)  progestins (21C) 
androgens (19C)  estrogens (18C)
Sertoli-Leydig-Germ Cell Crosstalk
 Germ cells
o no FSH or androgen receptors
o express estrogen & LH receptors
o locally produced estrogen by Sertoli
optimizes spermatogenesis

Leydig Cells
o express LH receptors
o testosterone production by Leydig cells
& LH are critical for spermatogenesis

Sertolic Cells
o express FSH & androgen receptors
o FSH & testosterone support
spermatogenesis via stimulation of
Sertolic cell fxn
*FSH & LH (via testosterone)– req’d for max sperm prod
*human males w/ inactivating mutation in FSH
receptors are fertile but small testes & low sperm count
MALE REPRODUCTIVE PHYSIOLOGY II
Fate of Testosterone
Testosterone (T) - produced in the Leydig cells in
response to LH
T = testosterone, SC = certoli cells
T has paracrine activity in SC
Can act on androgen receptors in SC producing new
mRNA and proteins
T can bind to ABP inc. local production of testosterone
in seminiferous tubules spermatogenesis
T can be converted to E2 via aromatization
E2 impt in sperm maturation
Glycoprotein Hormones
 LH, FSH, hCG, TSH
o Same  unit
Inhibins and Activins
 Inhibin A =  + A
 inhibin B =  + B
 activins = A + B only
Testosterone production by Leydig cell of Testis
T can be secreted into the blood stream and travels
bound to SHBG (made by the liver)
Loslely bound to albumin
~90% bounded
The rest are free and active
T converted to DHT by 5 a reductase
T can be converted to androstenedione via 17B HSD
Low conc of T in blood
Clinical correlation


Intratesticular testosterone needs to be 100X
higher than circulating levels to support
spermatogenesis

T administration ↑ levels circulating T hen
inhibits LH & not enough to accumulate in
testes needed to support spermatogenesis
(may cause infertility)


Androgens
 Affects male reproductive tract & 2o
characteristics (androgenic)
 Promotes skeletal muscle growth (anabolic)
 Main androgens
o T & DHT
Testosterone Action in Males
 Intrauterine differentiation of testes
 Mesonephric tubules to efferent ductules,
wolffian duct and testicular descent
 At puberty, remodels larynx → deepening of
voice
 Sertoli cell fxns
 Libido
 ↑hepatic VLDL and LDL and  HDL
 Deposition of abs adipose tissue
 ↑ muscle mass
 ↑RBC
T action in males (via local aromatization to E2)
 Closure of epiphyseal plates in long bones
 Bone remodelling (prevents osteoporosis)
 ↑insulin sensitivity
 ↑HDL and LDL & triglycerides
 Together with T & DHT feedback inhibition of
HP (hypothalamus-pituitary) axis
DHT actions in males
Local 5-reductase 2 expression
 Intrauterine dev’t of urogenital sinus into
prostatic & initial phallic parts of urethra,
prostate & bulbourethral glands & external
genitalia
 Descent of the testes
 At puberty, growth & fxn of prostate gland,
growth of penis, darkening & folding of
scrotum, growth of pubic, axillary, facial & body
hair
 With aging, hair recession and pattern baldness
Local 5-reductase 1 expression
 Sebaceous gland activity and acne
Testosterone & aging Male

Plasma levels  1% per yr (> 40 yo)
o Accelerates > 70 yo
bone density, muscle mass, hair growth,
appetite, libido & hematocrit
Reversible by administering T
LH not elevated
Male sexual arousal
Erection – parasymphatetic control
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

Nonadregenic-noncholinergic neurons
innervating vascular smooth muscles of helicine
arteries releases NO
Stimulation of guanylate cyclase by NO,
↑cGMP leading to cytosolic Ca and relaxation
& vasodilation of helicine arteries
Vasodilation ↑ blood flow in sinusoidal space
→ corpora cavernosa engorgement & erection
FEMALE REPRODUCTIVE PHYSIOLOGY I
Ovarian follicles
 basic unit of female reproductive bio
 contains single oocyte (ovum or egg)
 grow & develop → ovulation →single
competent oocyte
Primordial follicles
 begins in utero
Folliculogenesis
 primordial follicles → preovulatory follicles
 each follicle contains one 1o oocyte
o arrested in meiosis I & propase I
 lasts ~200 days / ~7 menstrual cycle
 before birth ~7M primordial follicles
 birth ~2M
 puberty ~300k
 ~450 (no. of menstrual cycle in woman’s life)
reach preovulatory stage
 At menopause primordial follicles ~1k
 Atresia
o Apoptosis of primordial and 1o, 2o,3o
follicles
Mature Graafian Follicle
 Theca (outermost) cells
o Blood supply
 Granulosa cells
o Will become corona radiata after
ovulation
 oocyte
Follicular life
 dependent on FSH
 Follicle type
o Primordial → 1o → 2o → 3o → Graafian
→ corpus Leteum (after ovulation)
 2o progression to meiosis II and metaphase II
secondary to LH surge
Menstrual Cycle
 Ovarian cycle
o Follicular phase (d 0-14)
o Luteal phase (d 14-28)
 Endometrial cycle
o Menses (d 0-14)
o Proliferative phase (d 4-14)
o Secretory phase (d 14-28)
Theca cells:
cholesterol (27C)  progestins (21C) 
androgens (19C)  STOP
Granulosa cells:
cholesterol (27C)  progestins (21C)  STOP
but can convert androgens (19C)  estrogens (18C)
provided by the Theca cells
FEMALE REPRODUCTIVE PHYSIOLOGY IV
General Biological Effects of Estrogen & Progesterone
Reproductive:
 Estrogen
o simulates internal & external rep.
organs
o triggers LH surge in late follicular phase
(+) feedback
o all times (-) feedback together w/
progesterone during ovarian cycle.
o Mediates proliferation & growth of
endometrium in the proliferative phase
of the endometrial cycle
o Progesterone mediates maturation
during secretry phase.