Ontogeny of estrogen receptors in human male and female fetal reproductive tracts

Differentiation. 2021 Mar-Apr:118:107-131. doi: 10.1016/j.diff.2020.10.001. Epub 2020 Oct 17.


This paper reviews and provides new observations on the ontogeny of estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2) in developing human male and female internal and external genitalia. Included in this study are observations on the human fetal uterine tube, the uterotubal junction, uterus, cervix, vagina, penis and clitoris. We also summarize and report on the ontogeny of estrogen receptors in the human fetal prostate, prostatic urethra and epididymis. The ontogeny of ESR1 and ESR2, which spans from 8 to 21 weeks correlates well with the known "window of susceptibility" (7-15 weeks) for diethylstilbestrol (DES)-induced malformations of the human female reproductive tract as determined through examination of DES daughters exposed in utero to this potent estrogen. Our fairly complete mapping of the ontogeny of ESR1 and ESR2 in developing human male and female internal and external genitalia provides a mechanistic framework for further investigation of the role of estrogen in normal development and of abnormalities elicited by exogenous estrogens.

Keywords: Estrogen receptors; Male and female external genitalia; Male and female internal genitalia.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Diethylstilbestrol / toxicity
  • Embryonic Development / genetics
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor beta / genetics*
  • Estrogens / genetics
  • Estrogens / metabolism*
  • Female
  • Fetus
  • Genitalia, Female / abnormalities
  • Genitalia, Female / growth & development
  • Genitalia, Female / metabolism*
  • Genitalia, Female / pathology
  • Genitalia, Male / abnormalities
  • Genitalia, Male / growth & development
  • Genitalia, Male / metabolism*
  • Genitalia, Male / pathology
  • Humans
  • Male


  • ESR1 protein, human
  • ESR2 protein, human
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • Diethylstilbestrol