Effects of maternal exposure to a low dose of diethylstilbestrol on sexual dimorphic nucleus volume and male reproductive system in rat offspring

J Toxicol Sci. 2005 Feb;30(1):7-18. doi: 10.2131/jts.30.7.

Abstract

Diethylstilbestrol (DES) was administered subcutaneously at 0.5, 1.5 or 4.5 microg/kg/day (DES 0.5, 1.5 and 4.5 groups, respectively) to pregnant SD rats daily on days 7-21 of gestation, to investigate its effects on the development and functions of the reproductive system in their male offspring. Of the 10 pregnant rats in the DES 4.5 group, only 1 delivered, and this rat could not suckle the pups. Rat pups in the DES 0.5 and 1.5 groups were autopsied at 1, 3, 6 and 15 weeks after birth. The testosterone concentrations in the DES 1.5 and 0.5 groups at 6 weeks were significantly decreased and the plasma LH concentrations were not altered. In the DES 1.5 group, DES treatment did not change the volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) in the male offspring, although this dose of DES increased the volume of SDN-POA in female offspring. The DES treatment altered frequencies in the cycles of the seminiferous tubules, and suppressed histological maturation in the epididymis and the prostate weight. These observations indicate that prenatally administered DES impairs testicular endocrine function continuously as well as pituitary function, but the induced low level of testosterone disrupts spermatogenesis and permanently inhibits the morphological development of epididymis and prostate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diethylstilbestrol / toxicity*
  • Dose-Response Relationship, Drug
  • Epididymis / drug effects
  • Female
  • Genitalia, Male / drug effects*
  • Male
  • Maternal Exposure
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Preoptic Area / drug effects*
  • Preoptic Area / pathology
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, LHRH / genetics
  • Sex Differentiation / drug effects*
  • Spermatogenesis / drug effects

Substances

  • RNA, Messenger
  • Receptors, LHRH
  • Diethylstilbestrol