Developmental estrogen exposures predispose to prostate carcinogenesis with aging

Gail S. Prins, Lynn Birch, Wan Yee Tang, Shuk Mei Ho

Research output: Contribution to journalReview articlepeer-review

180 Scopus citations


Prostate morphogenesis occurs in utero in humans and during the perinatal period in rodents. While largely driven by androgens, there is compelling evidence for a permanent influence of estrogens on prostatic development. If estrogenic exposures are abnormally high during the critical developmental period, permanent alterations in prostate morphology and function are observed, a process referred to as developmental estrogenization. Using the neonatal rodent as an animal model, it has been shown that early exposure to high doses of estradiol results in an increased incidence of prostatic lesions with aging which include hyperplasia, inflammatory cell infiltration and prostatic intraepithelial neoplasia or PIN, believed to be the precursor lesion for prostatic adenocarcinoma. The present review summarizes research performed in our laboratory to characterize developmental estrogenization and identify the molecular pathways involved in mediating this response. Furthermore, recent studies performed with low-dose estradiol exposures during development as well as exposures to environmentally relevant doses of the endocrine disruptor bisphenol A show increased susceptibility to PIN lesions with aging following additional adult exposure to estradiol. Gene methylation analysis revealed a potential epigenetic basis for the estrogen imprinting of the prostate gland. Taken together, our results suggest that a full range of estrogenic exposures during the postnatal critical period - from environmentally relevant bisphenol A exposure to low-dose and pharmacologic estradiol exposures - results in an increased incidence and susceptibility to neoplastic transformation of the prostate gland in the aging male which may provide a fetal basis for this adult disease.

Original languageEnglish (US)
Pages (from-to)374-382
Number of pages9
JournalReproductive Toxicology
Issue number3
StatePublished - Apr 2007
Externally publishedYes


  • Carcinogenesis
  • Development
  • Epigenetics
  • Estradiol
  • Estrogens bisphenol A
  • Methylation
  • Prostate
  • Steroid receptor

ASJC Scopus subject areas

  • Toxicology


Dive into the research topics of 'Developmental estrogen exposures predispose to prostate carcinogenesis with aging'. Together they form a unique fingerprint.

Cite this