[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Physiology](https://durgical.com/en/physiology/) › [Reproduction, pregnancy and the fetus](https://durgical.com/en/physiology/#s-repro) › Sex determination and differentiation [Physiology](https://durgical.com/en/physiology/) · [Reproduction, pregnancy and the fetus](https://durgical.com/en/physiology/#s-repro) # 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](https://durgical.com/en/anatomy/testis/) · [Epididymis](https://durgical.com/en/anatomy/epididymis/) · [Ductus deferens](https://durgical.com/en/anatomy/ductus-deferens/) · [Prostate](https://durgical.com/en/anatomy/prostate/) · [Scrotum](https://durgical.com/en/anatomy/scrotum/) · [Ovaries](https://durgical.com/en/anatomy/ovary/) · [Uterine tubes](https://durgical.com/en/anatomy/uterine-tube/) · [Body of uterus](https://durgical.com/en/anatomy/body-of-uterus/) · [Vagina](https://durgical.com/en/anatomy/vagina/) · [Clitoris](https://durgical.com/en/anatomy/clitoris/) · [Labia majora](https://durgical.com/en/anatomy/labium-majus-of-vulva/) ## Key points - SRY (Yp) → testis. No SRY → ovary (needs two X chromosomes to be maintained). - AMH (Sertoli) → Müllerian regression; testosterone (Leydig) → Wolffian ducts; DHT → penis, scrotum, prostate. - Female internal ducts develop without hormones; female external genitalia form when androgens are absent. - Congenital adrenal hyperplasia (21-hydroxylase deficiency) is the commonest cause of virilized 46,XX infants: normal uterus and ovaries, ambiguous external genitalia. - Hypospadias results from incomplete fusion of the urethral folds (less androgen action); cryptorchidism from failed testicular descent. ## 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 Hypothalamic–pituitary–testicular axis **Lesion** 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 | Signal | Source | Effect | | --- | --- | --- | | SRY | Y chromosome | Bipotential gonad becomes testis | | AMH | Sertoli cells | Regression of the Müllerian ducts | | Testosterone | Leydig cells | Wolffian ducts: epididymis, vas deferens, seminal vesicles | | [DHT](https://durgical.com/en/conditions/hypospadias/) | Testosterone via 5α-reductase | Penis, scrotum, prostate | | [Excess androgen in a 46,XX fetus](https://durgical.com/en/conditions/congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency/) | Fetal 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. ## Memory aid SRY makes the testis; Sertoli Stops Müller, Leydig Leads Wolff, DHT Draws the outside. ## 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. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/physiology/sex-determination-and-differentiation/) ## See it in 3D The structures of Durgical's 3D anatomy where it happens. - [Testes](https://durgical.com/en/anatomy/testis/) - [Epididymis](https://durgical.com/en/anatomy/epididymis/) - [Ductus deferens](https://durgical.com/en/anatomy/ductus-deferens/) - [Prostate](https://durgical.com/en/anatomy/prostate/) - [Scrotum](https://durgical.com/en/anatomy/scrotum/) - [Ovaries](https://durgical.com/en/anatomy/ovary/) - [Uterine tubes](https://durgical.com/en/anatomy/uterine-tube/) - [Body of uterus](https://durgical.com/en/anatomy/body-of-uterus/) - [Vagina](https://durgical.com/en/anatomy/vagina/) - [Clitoris](https://durgical.com/en/anatomy/clitoris/) - [Labia majora](https://durgical.com/en/anatomy/labium-majus-of-vulva/) ## Related topics - [Testosterone and its actions](https://durgical.com/en/physiology/testosterone-and-its-actions/) - [The male gonadal axis and spermatogenesis](https://durgical.com/en/physiology/the-male-gonadal-axis-and-spermatogenesis/) - [Puberty](https://durgical.com/en/physiology/puberty/) - [The adrenal cortex: zones, hormones and androgens](https://durgical.com/en/physiology/the-adrenal-cortex-zones-hormones-and-androgens/) ## Related conditions - [Congenital adrenal hyperplasia due to 21-hydroxylase deficiency](https://durgical.com/en/conditions/congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency/) - [Hypospadias](https://durgical.com/en/conditions/hypospadias/) - [Cryptorchidism (undescended testis)](https://durgical.com/en/conditions/cryptorchidism/) ## In Biochemistry - [21-Hydroxylase (CYP21A2)](https://durgical.com/en/biochemistry/enzymes/21-hydroxylase/) - [Adrenal enzymes and congenital adrenal hyperplasia](https://durgical.com/en/biochemistry/topics/adrenal-enzymes-and-congenital-adrenal-hyperplasia/) - [17-Hydroxyprogesterone (17-OHP)](https://durgical.com/en/biochemistry/molecules/17-hydroxyprogesterone/) - [Aromatase (CYP19A1)](https://durgical.com/en/biochemistry/enzymes/aromatase/) [← All of physiology](https://durgical.com/en/physiology/) 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](https://openstax.org/books/anatomy-and-physiology-2e/pages/27-3-development-of-the-male-and-female-reproductive-systems/) (OpenStax (Rice University), 2022); [21-hydroxylase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/21-hydroxylase-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [Hypospadias Urogenital Reconstruction](https://www.ncbi.nlm.nih.gov/books/NBK564407/) (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). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/physiology/sex-determination-and-differentiation/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/physiology/sex-determination-and-differentiation/