Sexual Differentiation By Vamsi Krishna M urthy 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: 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
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 protokidney T he gonad at this stage (pre 7-weeks) has a medullary and cortical region (inner and outer )( testes develop during the 7 th week of gestation, ovaries develop during the 13 th to 16 th 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
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 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
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 wolffian With no hormones, the mullerian duct develops, and the wolffian duct undergoes programmed cell death (regresses and degenerates) This causes formation of female internal morphology Mullerian system becomes fallopian tubes, uterus, and cervix With testes present: Leydig cells produce testosterone, cause development of wolffian ducts (turn off programmed cell death) Wolffian ducts become vas deferens, seminal vessicles , and prostate gland Sertoli cells produce Mullerian inhibitory hormone(MIH), cause regression of mullerian ducts 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 T E 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: 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
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