Gestational and lactational exposure to ethinyl estradiol, but not bisphenol A, decreases androgen-dependent reproductive organ weights and epididymal sperm abundance in the male long evans hooded rat

Toxicol Sci. 2008 Apr;102(2):371-82. doi: 10.1093/toxsci/kfm306. Epub 2007 Dec 20.

Abstract

Many chemicals released into the environment are capable of disrupting normal sex steroid balance, including the oral contraceptive ethinyl estradiol (EE) and the plastic monomer bisphenol A (BPA). EE and BPA are reported to impair reproductive organ development in laboratory animals; however, effects of lower doses of these chemicals have been debated. The goal of the current study was to determine whether relatively low oral doses of EE or BPA would alter male reproductive morphology and associated hormone levels of Long Evans hooded rat. Dams were gavaged with corn oil vehicle, EE (0.05-50 mug/kg/day) or BPA (2, 20, and 200 mug/kg/day) during pregnancy through lactation from gestational day 7 to postnatal day (PND) 18. Anogenital distance was measured at PND2 and nipple retention was measured at PND14 in male pups. Male offspring were euthanized beginning at PND150, and sera and organs were collected for analyses. Adult body weight was significantly decreased in males exposed to 50 mug EE/kg/day. Developmental EE exposure reduced androgen-dependent tissue weights in a dose-dependent fashion; for example, seminal vesicle and paired testes weights were reduced with >/= 5 mug EE/kg/day. Epididymal sperm counts were also significantly decreased with 50 mug EE/kg/day. In contrast, treatment with 2, 20, or 200 mug BPA/kg/day or EE at 0.05-1.5 mug/kg/day did not significantly affect any male endpoint in the current study. These results demonstrate that developmental exposure to oral micromolar doses of EE can permanently disrupt the reproductive tract of the male rat.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anal Canal / abnormalities
  • Anal Canal / drug effects
  • Anal Canal / pathology
  • Animals
  • Animals, Newborn
  • Benzhydryl Compounds
  • Body Weight / drug effects
  • Dose-Response Relationship, Drug
  • Environmental Pollutants / toxicity*
  • Epididymis / drug effects
  • Epididymis / pathology
  • Estrogens / toxicity*
  • Ethinyl Estradiol / toxicity*
  • Female
  • Genitalia, Male / abnormalities
  • Genitalia, Male / drug effects*
  • Genitalia, Male / pathology
  • Lactation / drug effects*
  • Male
  • Maternal Exposure
  • Organ Size / drug effects
  • Phenols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / pathology
  • Rats
  • Rats, Long-Evans
  • Seminal Vesicles / drug effects
  • Seminal Vesicles / pathology
  • Sperm Count
  • Spermatozoa / drug effects
  • Spermatozoa / pathology
  • Testis / drug effects
  • Testis / pathology

Substances

  • Benzhydryl Compounds
  • Environmental Pollutants
  • Estrogens
  • Phenols
  • Ethinyl Estradiol
  • bisphenol A