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Sex determination and differentiation !

  • Concept
  • For completeness

A gene on the Y chromosome turns the early gonad into a testis; its hormones then build the male tract. Without them, the female pattern develops.

Updated 2026-11-01

Also called: SRY, Wolffian and Müllerian ducts, Differences of sex development

See it in 3D: Testes · Epididymis · Ductus deferens · Prostate · Scrotum · Ovaries · Uterine tubes · Body of uterus · Vagina · Clitoris · Labia majora

What it is

Until about week 6 the gonads and ducts are the same in both sexes. SRY on the Y chromosome steers the gonad to a testis. Sertoli cells make anti-Müllerian hormone (AMH), which removes the Müllerian ducts; Leydig cells make testosterone, which keeps the Wolffian ducts, and DHT shapes the external genitalia. Without a testis, the ovary forms, the Wolffian ducts regress and the Müllerian ducts form the tubes, uterus and upper vagina.

Key facts

  • Testosterone production in the fetal testis is first driven by placental hCG, later by fetal LH.
  • External genitalia are formed by about week 12; later androgen deficiency gives a small penis but no ambiguity.
  • Testicular descent: transabdominal phase (INSL3, gubernaculum) and inguinoscrotal phase (androgen-dependent).
  • Homologues: genital tubercle → glans penis or clitoris; urethral folds → spongy urethra or labia minora; labioscrotal swellings → scrotum or labia majora.

Hormone axes and feedback

Hormone axes and feedback: Hypothalamic–pituitary–testicular axis Kisspeptin · pulsed GnRH (continuous → suppresses)−−−++LH+FSH++HypothalamusGnRH (pulsatile)Anterior pituitary (gonadotrophs)LHFSHLeydig cellsTestosteroneSertoli cellsInhibin BTarget tissuesSpermatogenesis · male traits

Hypothalamic–pituitary–testicular axisLesion None (normal)

Tap a box to see the hormone, or choose a lesion to see the lab pattern.

  • Stimulates (+)
  • Inhibits / negative feedback (−)
  • Level ↑
  • Level ↓
Tap Leydig and Sertoli cells: the same two cells build the male tract before birth with testosterone and AMH.

Signal, source and effect

SignalSourceEffect
SRYY chromosomeBipotential gonad becomes testis
AMHSertoli cellsRegression of the Müllerian ducts
TestosteroneLeydig cellsWolffian ducts: epididymis, vas deferens, seminal vesicles
DHTTestosterone via 5α-reductasePenis, scrotum, prostate
Excess androgen in a 46,XX fetusFetal adrenal (CAH)Virilized external genitalia, normal uterus and ovaries

Clinical notes

  • Classic 21-hydroxylase deficiency: high 17-hydroxyprogesterone, salt wasting and shock in the first weeks; newborn screening detects it.
  • Complete androgen insensitivity (46,XY): female external genitalia, no uterus (AMH works) and testes in the abdomen or groin.
  • Turner syndrome (45,X) gives streak ovaries; Klinefelter (47,XXY) gives small testes and infertility.

Test yourself

Think of the answer, then tap the question to see it.

A 46,XY person has female external genitalia, a short blind vagina and no uterus. What explains the missing uterus?

Complete androgen insensitivity: the testes still make AMH, which removes the Müllerian ducts, but tissues cannot respond to testosterone or DHT.

Why does 21-hydroxylase deficiency virilize a 46,XX fetus but leave the uterus normal?

Cortisol synthesis is blocked, ACTH rises and precursors are shunted to adrenal androgens, which virilize the external genitalia. No AMH is made, so the Müllerian ducts develop normally.

What would a 46,XY fetus with absent Sertoli cell AMH but normal testosterone have?

Male external genitalia and Wolffian ducts plus a uterus and tubes (persistent Müllerian duct syndrome), often found during hernia repair or for cryptorchidism.

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See it in 3D

The structures of Durgical's 3D anatomy where it happens.

In Biochemistry

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Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: 27.3 Development of the Male and Female Reproductive Systems (OpenStax (Rice University), 2022); 21-hydroxylase deficiency: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Hypospadias Urogenital Reconstruction (StatPearls (NCBI Bookshelf), 2023); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 81). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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