It’s a boy! Or is it? Variability in human gender development.

Cynthia J. Gill, Ph.D.University of Texas

Androgen-receptor deficient male (TFM)

Sex determination and differentiation

Objectives• Distinguish gender as defined by various criteria.• State the critical factors for reproductive system differentiation.• Predict the result of variations during development.

Chromosomal sex (genetic sex)Chromosomal sex (genetic sex)XX or XY, Y has SRY geneXX or XY, Y has SRY gene

Gonadal sex (gametic sex)Gonadal sex (gametic sex)ovary or testis (eggs or sperm)ovary or testis (eggs or sperm)

Morphological sexMorphological sex(internal and external genitalia,(internal and external genitalia,

2° sex characteristics)2° sex characteristics)

Behavioral sexBehavioral sex(brain morphology, behavior)(brain morphology, behavior)

Hormonal sexHormonal sexestrogen or testosteroneestrogen or testosterone

Gender identityGender identity““I am male” or “I am female”I am male” or “I am female”

Gonad and internal genitalia differentiation

Cascade of events in development of male

Synthesis pathway for steroid hormones

5 reductase

Sex differentiation: cascade event rules

• SRY gene determines testes development• Testes make testosterone and MIS• Testosterone differentiates Wolffian ducts• MIS inhibits Müllerian duct differentiation• Testosterone masculinizes external genitalia but full differentiation is by DHT

Identify the sex determination and/or differentiation:

1. XY 2. XX3. XY with absent SRY gene4. XX with SRY gene5. XY with no functional androgen (T & DHT) receptor6. XX with hypersecretion of testosterone7. XY with no 5 reductase enzyme

Gonads: testes or ovaries?Internal genitalia: Wolffian or Müllerian duct development?External genitalia: male-like or female-like?

How would you decide who is ‘male’ and who is ‘female’ for gender-separate sports events in the Olympics?

Pathways of adrenal hormone synthesis.

Sexual Differentiation: gonads

• Every embryo initially has two undifferentiated primordial gonads

– The Y chromosome directs development into male gonads, testes

– The absence of the Y chromosome causes development into the

female gonad, or ovary

Sexual differentiation: Internal Genitalia

• Each embryos has two sets of internal organs, the Wolffian and the

Mullerian ducts

– The Wolffian ducts are the precursors of the male internal

genitalia, and develop under the influence of testosterone

– The Mullerian ducts are the precursors of the female genitalia and

develop unless Mullerian inhibiting substance is present

Sexual differentiation: External Genitalia

• Both male and female embryos have protruding tufts of flesh called the

genital tubercle, urethrogenital folds, and labioscrotal swellings

• In the male body, testosterone is converted to dihydrotestosterone,

the androgen that converts the embryonic external genitalia into the penis

and scrotum

• In the absence of dihydrotestosterone, the external genitalia become

female