Sexual differentiation in humans occurs through a multi-step process determined by chromosomal, gonadal, hormonal, and morphological sex. The presence or absence of the SRY gene on the Y chromosome triggers testis or ovary development from the initially undifferentiated gonad. The testes secrete testosterone and Müllerian inhibiting hormone which masculinize the internal and external genitalia as well as the brain, preventing female development. In the absence of these hormones, the individual develops along female lines. Disorders can occur at each stage of differentiation, resulting in intersex conditions or abnormalities in sexual development.

1. Sexual
Differentiation
By
Vamsi Krishna Murthy Ginjupalli
UNIVERSITY OF SIENA

2. Sexual Differentiation
chromosomal sex
gonadal sex
hormonal sex
morphological sex
differences in physiology

3. Sexual Differentiation
chromosomal sex
gonadal sex
hormonal sex
morphological sex
differences in physiology

4.  each human cell contains 46 chromosomes, occurring in pairs
 23 pairs of chromosomes
 22 autosomes (determines e.g., hair color)
 23rd pair are the sex chromosomes
male: XY
female: XX
Chromosomal sex
 Germ cells:
 male: sperm - contains “X” or “Y”
 female: ovum - contains an “X”
 “Y” chromosome contains less genetic
material than “X” chromosome

5. Sexual Differentiation
chromosomal sex
gonadal sex
hormonal sex
morphological sex
differences in physiology

6. Gonadal
Differentiation
Undifferentiated gonad develops as a
‘germinal ridge’ off of the
protokidney
The gonad at this stage (pre 7-weeks)
has a medullary and cortical region
(inner and outer)(testes develop
during the 7th week of gestation,
ovaries develop during the 13th to 16th
week)
Without TDF input, the cortical
region will develop into an ovary, and
the medullary region will regress
SRY causes development of the
medullary region into a testis, and
development proceeds from there,
resulting from the hormones secreted
by the gonads

7. Sexual Differentiation
chromosomal sex
gonadal sex
hormonal sex
morphological sex
differences in physiology

8. Ovaries: fairly quiescent during embryogenesis. They secrete very low levels of
estrogens, but don’t produce significant quantities of hormones until puberty
to repeat: in the absence of hormones from a testis (differentiated because of
SRY), morphological, neural, and behavioral development is female
Testes: produce testosterone (from the leydig cells) and proteins (mullerian
inhibiting hormone MIH from the sertoli cells)
hormonal sex

9. Sexual Differentiation
chromosomal sex
gonadal sex
hormonal sex
morphological sex
differences in physiology

10. Sexual Differentiation
chromosomal sex
gonadal sex
hormonal sex
morphological sex
differences in physiology
Ductal system
External genitalia
Differentiation of the
brain

11. Mullerian and Wolffian Duct Systems
cervix

12. The progenitors for the duct systems are present for both male and females
embryologically
In contrast to gonadal development, where one gonad becomes either male or female.
mullerian vs wolffian
1) With no hormones, the mullerian duct develops, and the wolffian duct undergoes
programmed cell death (regresses and degenerates)
1) This causes formation of female internal morphology
2) Mullerian system becomes fallopian tubes, uterus, and cervix
2) With testes present:
1) Leydig cells produce testosterone, cause development of wolffian ducts (turn
off programmed cell death)
1) Wolffian ducts become vas deferens, seminal vessicles, and prostate gland
2) Sertoli cells produce Mullerian inhibitory hormone(MIH), cause regression of
mullerian ducts
1) If the sertoli cells fail to produce MIH, a male can have both male and
female internal structures
Mullerian and Wolffian Duct Systems

13. External
Genitalia
Development of male external genitalia is
dependent on dihydrotestosterone (DHT), an
androgen
-The skin of the genitalia contains the
enzyme necessary to convert testosterone to
DHT (5-alpha reductase)
-The testis produces androgens, and in the
genital area, that is converted to DHT, causing
masculinization of the external genitalia
(fusion of the genital swelling)
Both males and females have this enzyme (5-
alpha reductase) in the developing genitalia, but
females have no T to convert at this time, so
no DHT produced
-If female is accidentally producing T, she can
have masculinized genitalia at birth
- If male does not produce the enzyme,
external genitalia will be female.

14. Male:
 Testosterone secreted into the blood reaches the brain
 testosterone converted to estradiol and dihydrotestosterone
in the brain
 estradiol masculinizes the brain
Female:
 alpha-fetoprotein binds to estradiol
 prevents estradiol from entering the brain
 protects female brains from being masculinized by estradiol
Brain Differentiation

15. Brain Differentiation
testis
testosterone
TE
BRAIN
Tonic secretion of
GnRH in puberty
IN FEMALES?
Alpha-fetoprotein
Blocks estrogen in blood from entering brain

16. Brain Sexual Chemistry

17. Summary
Undifferentiated
gonad
Y-chromosome:
SRYTDF
Embryonic
Testis
Sertoli cells
Leydig cells
MIH Mullerian duct
regression
testosterone Wollfian duct
DHT
Masculinization of
external genitalia
estrogen
Masculinization
of the brain

18. Sexual Differentiation
chromosomal sex
gonadal sex
hormonal sex
morphological sex
differences in physiology

19. Pathophysiology
• Male Anomalies
• Androgen insensitivity syndrome
• No functional androgen receptors
• 5-alpha reductase deficiency
• Cannot produce DHT
• Female Anomalies
• Masculinization
• Exogenous treatment with androgenic steroids
• Endogenous production of androgenic steroids (CAH)
• Chromosomal Abnormalities
• Turner Syndrome
• Lack of (or damage to) second X chromosome
• Kleinfelter Syndrome (XXY)
• XYY

20. thank you for your attention
vamsi