3. Sexual Differentiation

3.1      Overview

·       Sex differentiation: the process by which a developing embryo or fetus develops into a male or female sexual phenotype.

·       It's a complex process involving genetic, hormonal, and anatomical changes that lead to the development of distinct male and female characteristics

  • Early embryo has indifferent gonads capable of developing into either testes or ovaries.
  • The gonadal ridge can develop into either testes or ovaries.
    • Supporting structures include the mesonephric (Wolffian) and paramesonephric (Müllerian) ducts
  • Presence or absence of SRY gene and testicular hormones determines the direction of development.

  • Key Stages of Sexual Differentiation
    • Chromosomal sex (XX or XY)
    • Gonadal sex (ovaries or testes)
    • Phenotypic sex (internal & external genitalia)
    • Secondary sexual characteristics

3.2 Differentiation of Internal Genitalia (Gonadal sex)

·       Development depends on presence or absence of testes and their hormones.

·      Male Differentiation

o   Triggered by SRY gene → TDF → Sertoli cell development.

o   Sertoli cells secrete Anti-Müllerian Hormone (AMH) → regression of Müllerian ducts.

o   Leydig cells produce testosterone, promoting the development of:

§  Wolffian ducts → epididymis, vas deferens, seminal vesicle.

§  Dihydrotestosterone (DHT) forms external genitalia (penis, scrotum, prostate).

·       Female Pathway (No Testes)

o   In absence of SRY and AMH → Müllerian ducts form:

§  Fallopian tubes

§  Uterus

§  Upper vagina

o   No testosterone → Wolffian ducts regress.

·       Role of the SRY Gene

o   Located on the Y chromosome.

o   Codes for Testis-Determining Factor (TDF).

o   Initiates differentiation of Sertoli cells → triggers testis formation.

o   Absence of SRY allows ovarian development to occur by default

3.3 Differentiation of External Genitalia (Phenotypic sex)

·       Driven by androgen exposure from weeks 8–12.

·       Male

o   DHT (from testosterone) causes formation of:

§  Penis

§  Scrotum

§  Prostate

·       Female

o   In absence of DHT:

§  Clitoris

§  Labia majora/minora

§  Lower vagina

3.4      Regulation of Sexual Differentiation

Regulation in Males

·       Sertoli Cells

o   Produce Anti-Müllerian Hormone (AMH)

o   Causes regression of Müllerian ducts, preventing female internal organ formation.

·       Leydig Cells

o   Produce testosterone

o   Testosterone converts Wolffian ducts into:

§  Epididymis

§  Vas deferens

§  Seminal vesicles

o   Testosterone is converted by 5α-reductase to Dihydrotestosterone (DHT)

·       DHT and External Genitalia

o   DHT is responsible for:

§  Development of penis

§  Formation of scrotum

§  Growth of the prostate

Regulation in Females

·       Absence of SRY

o   Gonad → ovary.

·       Absence of AMH

o   Müllerian ducts develop into:

§  Fallopian tubes

§  Uterus

§  Upper vagina

·       Absence of Testosterone

o   Wolffian ducts regress.

·       In the absence of DHT, the external phenotype becomes:

o   Clitoris

o   Labia majora/minora

o   Lower vagina