The development of the reproductive system begins with the formation of undifferentiated gonads and the paired mesonephric and paramesonephric ducts. Further differentiation of the gonads is dependent on the presence or absence of the SRY gene on the Y chromosome, which stimulates differentiation of the testes in male individuals. Testosterone (produced by Leydig cells) drives the differentiation of the mesonephric ducts into male internal sex organs and dihydrotestosterone drives the differentiation of male external genitalia. Mullerian inhibitory factor (MIF), produced by Sertoli cells, suppresses the differentiation of the paramesonephric ducts. In female individuals, the absence of MIF allows differentiation of the paramesonephric ducts into the female internal organs, and estrogen drives the differentiation of female external genitalia. The absence of testosterone prevents the differentiation of the mesonephric ducts in female individuals. The descent of the gonads, which is much more prominent in male individuals, is facilitated by the gubernaculum, which promotes the descent of the testes from their initial retroperitoneal location into the scrotum.
- Weeks 1–6: No sexual differentiation is apparent (no phenotypical differences).
- Week 6–7: Differentiation of the mesonephric and paramesonephric ducts begins.
- Week 12: Development of the external genitalia is complete.
- Week 20: Phenotypic differentiation is complete.
- Week 33: Descent of the gonads is complete.
Chromosomal sex: determined by chromosome count (see “ ”)
- Female individuals have XX.
- Male individuals have XY.
- See “ ”.
- Gonadal sex: development of the undifferentiated gonads into testes or ovaries
- Phenotypic sex
- Description: development of the undifferentiated gonads into testes or ovaries
The Y chromosome contains the SRY gene.
- The SRY gene encodes testis-determining factor (TDF): transcription factor necessary for testes development.
- TDF stimulates the proliferation and differentiation of the primitive sex cords into testes.
- Autosomal SOX9 gene: transcription regulator also involved in testes differentiation that is upregulated by SRY gene
- Absence of Y chromosome and presence of WNT4 gene → ovarian development (default)
- The Y chromosome contains the SRY gene.
- Clinical significance
Ductal sex differentiation
- Description: development of the embryonic ducts into the internal sex organs
- Timeline: starts in weeks 7–8
- Both male and female embryos have mesonephric ducts and paramesonephric ducts.
- Differentiation relies on the MIF) and testosterone. r (
- Male individuals
- Female individuals
|Overview of ductal sex differentiation|
|Embryonic structure||General description|| |
Male individuals (starting the 7th week)
Female individuals (starting the 8th week)
|Paramesonephric ducts (Mullerian ducts)|| |
Mesonephric ducts (Wolffian ducts)
- (both ovarian and testicular tissue are present)
See “” and “ ”.
- Incomplete fusion: bicornuate uterus
- No fusion: uterus didelphys
- Single paramesonephric duct: unicornuate uterus
- No paramesonephric ducts development: Mullerian agenesis (or Mayer-Rokitansky-Küster-Hauser syndrome)
- See “”.
The “default” sex in sexual development is female.
In the testes, Leydig cells Lead to male differentiation, and Sertoli cells Suppress female differentiation.
“SEED” stands for the derivatives of the mesonephric duct in male individuals: Seminal vesicles, Epididymis, Ejaculatory duct, Ductus deferens.
- Description: development of the embryonic ducts into the external genitalia
- Timeline: starts in week 9
- Mechanism: primarily driven by the presence or absence of estradiol and dihydrotestosterone
|Overview of external genitalia and urogenital differentiation|
|Embryonic structure|| |
| || |
- Clinical significance
Descent of gonads
- Timeline: complete by week 33 
|Overview of gonadal descent|
|Embryonic structure||General description ||Male remnant||Female remnant||Clinical significance|
|Processus vaginalis|| || |