Introduction

Sexual differenciaton by default follows a pathways for development of female internal and external genitalia, requiring no active intervention. Endocrine activity of the testes, production of Androgens by Leydig cells and Mullerian Inhibiting hormone by Sertoli cells, is required for sexual differenciation to be diverted down the male genitalia development pathway.

Internal Genetalia

Male: The primitive male reproductive tract The Wolffian Duct developes from the Mesonephric Duct
Female: The primitive female reproductive tract Mullarian Ducts develop from the Paramesonephric Duct
This is dependent on appropriate hormonal influence.

Male

MIH from Sertoli cells and Androgens from Leydig cells prevent spontaneous development of female internal genetalia.
Androgens actively maintain Wolffian Ducts, which give rise to male internal genetalia:
- Epididymis
- Vas Deferens
- Vesicular Glands/ Seminal Vesicles
MIH causes Mullarian Ducts to regress

Female

Wolffian Ducts spontaneously regress in absence of Androgens.
Mullarian Ducts persist to give rise to female internal genetalia:
- Oviducts
- Uterus
- Cervix
- Cranial Vagina
Normal Ovarian activity is NOT essential for the development of normal female internal genetalia.

External Genetalia

Male

Potential to develop male of female external genetalia. Testosterone is required to develop male external genetalia.
Androgen secretion from the Testes induces:
- Urethral folds to fuse to allow enclosure of the urethral tube. This, together with the cells from the genital swelling, forms the shaft of the Penis.
- Genital swellings fuse in the midline to allow formation of the Scrotum
- Genital Tubercle expands to give rise to the Glans Penis

Female

Development is ensured by the absence of Testosterone, it is independent of Ovarian endocrine activity.
Urethral folds and Genital Swellings remain separate to form the Labia Minora and Majora.
Genital tubercle forms the Clitoris

Exposure of the female tract to Androgens will masculinise external genetalia.
Failure of proper endocrine communication between the gonads, internal and external genitalia can lead to dissociation of gonadal and genital sex.

Sexual Differentiation of the Brain

Male

Testosterone secreted into the blood reaches the brain.
Converted to Dehydrotestosterone and Oestradiol by Aromatase enzymes in the Hypothalamus.
Oestradiol masculinises the brain

Female

Alpha Fetoprotein binds Oestradiol, preventing it from crossing the blood-brain barrier.
Oestradiol cannot access the Hypothalamus
Protects female brain from masculising effects of Oestradiol.