Sex determination,�Sex differentiation
&
Puberty
Dr. K. Jaiganesh
Professor & Head of Physiology - MGMCRI
Deputy Registrar - SBV
Components of sexual development and sexual identity are:
Sex Determination - genetic differentiation (genotype)
Sex Differentiation -
Physical - gonadal differentiation
- genital differentiation (phenotype)
Psychological
Sociological
From Female
From Male
22 X
22 X
22 Y
44
44
From Male
44 XX
Girl
44 XX
Boy
XX or XY
Testes or Ovary
Genitalia development
Role of Y chromosome
Role of Y-chromosome in Testicular differentiation
Two Transcription genes
1.Gene for testicular differentiation
Located at the short arm of Y chromosome is SRY (sex determining region of the Y chromosome)
SRY gene encodes the Testis Determining Factor (TDF) which triggers testicular differentiation
2.Gene for formation of Mullerian duct inhibitory substance (MIS)
Bipotential Gonads
Primitive Gonad: Bipotential
Cortex
Medulla
Male [Testes]
Female [Ovary]
Wolffian duct
Male genitalia
Testosterone
Mullerian duct
Female genitalia
Primitive Gonad: Male: Y chromosome is present
Cortex
Medulla
Male [Testes]
Female [Ovary]
Wolffian duct
Male genitalia
Testosterone
Mullerian duct
Female genitalia
MIS
Primitive Gonad: Male: Y chromosome is absent
Cortex
Medulla
Male [Testes]
Female [Ovary]
Wolffian duct
Male genitalia
Testosterone
Mullerian duct
Female genitalia
No MIS
Regulation of development of Internal genitalia
When stimulated with Testosterone, become the epididymis,
vas deferens, seminal vesicles and ejaculatory ducts
In the absence of Sertoli cell Mullerian-inhibiting substance
(MIS) become the fallopian tubes, uterus, cervix and upper
one third of vagina
Summary of TDF
2. Activates Sertoli cells to produce Mullerian inhibiting hormone, causing Mullerian duct degeneration
3. Stimulates Leydig cells to secrete testosterone, which then directs development of the Wolffian ducts towards epididymis, vas deferens and seminal vesicles
- Testosterone conversion to dihydrotestosterone (DHT) - (by 5 –alpha reductase) directs development of the urethra, prostate gland and penis
What if you are XY?
Y chromosome (SRY region; TDF gene) is present.
TDF is released
Medulla of Gonad develops towards testes
In the presence of testosterone – Wolffian duct system develops in to male external genitalia
In presence of MIS – Mullerian duct degenerates.
What if you are XX?
Y chromosome (SRY region; TDF gene) is absent.
No TDF is released to form testis
Cortex of Gonad develops towards ovary
In the absence of testosterone – Wolffian duct system degenerates
In absence of MIS – Mullerian ducts continue to develop
towards fallopian tubes, uterus, and upper vagina.
Time frame for development of fetal male reproductive system
- Regression of Mullerian ducts
Summary of sex determination:
At fertilization - have genotypic sex determination
At 6-7 weeks - have gonadal sex determination
- if TDF present - Male gonad develops
- if TDF absent - Female gonad develops
TDF - Referred to a the “master switch”
How do we go from gonadal sex to phenotypic sex?
Regulation of development of External Genitalia
44 + XY
Male
22 +Y
22 + X
BIPOTENTIAL GONAD
SRY
EMBRYONIC TESTIS
ADULT TESTIS
MIS
T
DHT
DHT
No female internal genitalia
Male internal genitalia
Male external genitalia
Male sec.sex.characters
44 + XX
Female
22 + X
22 + X
BIPOTENTIAL GONAD
EMBRYONIC OVARY
ADULT OVARY
Estrogens
Female internal genitalia
Female external genitalia
Female sec.sex.characters
X Inactivation
- one X chromosome in each female cell is inactivated
- inactivation is a random process
Some cells - turn off dad’s X
Some cells - turn off mom’s X
Bottom line: X-inactivation balances (compensates) dosage of X-linked genes between male and female cells
Inactivated X chromosome can be seen in females cells as the Barr body - Murray Barr (1949)
How is the dosage for X-linked genes adjusted to be equivalent in males and females?
Summary: Lyons Hypothesis
- Only one X chromosome is active in somatic cells
chromosome
- Inactivation occurs early in embryonic development
equivalent for X-linked genes
- Exception - germ line cells – both X remain active
types
Significance of Barr body
1.Identification of sex genotype
The sex (female) can be identified by a cytological Test in the following cells:
- Epithelial cells of epidermal spinous layer
- Buccal mucous cells
- Mucosal cells of vagina
- Polymorphonuclear cells (in 15 % seen as
drumsticks projecting from the nucleus)
2.To identify abnormal genotypes (cells with 2 or 3 X chromosomes show 2 or 3 Barr bodies)