Sexual Differentiation

By

Vamsi Krishna Murthy Ginjupalli

UNIVERSITY OF SIENA

Sexual Differentiation

chromosomal sex

gonadal sex

hormonal sex

morphological sex

differences in physiology

Sexual Differentiation

chromosomal sex

gonadal sex

hormonal sex

morphological sex

differences in physiology

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: XYfemale: 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

Sexual Differentiation

chromosomal sex

gonadal sex

hormonal sex

morphological sex

differences in physiology

Gonadal Differentiation

Undifferentiated gonad develops as a ‘germinal ridge’ off of the protokidneyThe 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 regressSRY causes development of the medullary region into a testis, and development proceeds from there, resulting from the hormones secreted by the gonads

Sexual Differentiation

chromosomal sex

gonadal sex

hormonal sex

morphological sex

differences in physiology

Ovaries: fairly quiescent during embryogenesis. They secrete very low levels of estrogens, but don’t produce significant quantities of hormones until pubertyto 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

Sexual Differentiation

chromosomal sex

gonadal sex

hormonal sex

morphological sex

differences in physiology

Sexual Differentiation

chromosomal sex

gonadal sex

hormonal sex

morphological sex

differences in physiology

Ductal system

External genitalia

Differentiation of the brain

Mullerian and Wolffian Duct Systems

cervix

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 wolffian1) 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 morphology2) 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

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.

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

Brain Differentiation

testis

testosterone

TE

BRAIN

Tonic secretion of GnRH in puberty

IN FEMALES?Alpha-fetoprotein

Blocks estrogen in blood from entering brain

Brain Sexual Chemistry

Summary

Undifferentiated gonad

Y-chromosome:SRYTDF

Embryonic Testis

Sertoli cells

Leydig cells

MIH Mullerian ductregression

testosterone Wollfian duct

DHT

Masculinization ofexternal genitalia

estrogen

Masculinization of the brain

Sexual Differentiation

chromosomal sex

gonadal sex

hormonal sex

morphological sex

differences in physiology

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

thank you for your attention

vamsi