Developmental exposure to xenoestrogens at low doses alters femur length and tensile strength in adult mice

Biol Reprod. 2012 Mar 19;86(3):69. doi: 10.1095/biolreprod.111.096545. Print 2012 Mar.

Abstract

Developmental exposure to high doses of the synthetic xenoestrogen diethylstilbestrol (DES) has been reported to alter femur length and strength in adult mice. However, it is not known if developmental exposure to low, environmentally relevant doses of xenoestrogens alters adult bone geometry and strength. In this study we investigated the effects of developmental exposure to low doses of DES, bisphenol A (BPA), or ethinyl estradiol (EE(2)) on bone geometry and torsional strength. C57BL/6 mice were exposed to DES, 0.1 μg/kg/day, BPA, 10 μg/kg/day, EE(2), 0.01, 0.1, or 1.0 μg/kg/day, or vehicle from Gestation Day 11 to Postnatal Day 12 via a mini-osmotic pump in the dam. Developmental Xenoestrogen exposure altered femoral geometry and strength, assessed in adulthood by micro-computed tomography and torsional strength analysis, respectively. Low-dose EE(2), DES, or BPA increased adult femur length. Exposure to the highest dose of EE(2) did not alter femur length, resulting in a nonmonotonic dose response. Exposure to EE(2) and DES but not BPA decreased tensile strength. The combined effect of increased femur length and decreased tensile strength resulted in a trend toward decreased torsional ultimate strength and energy to failure. Taken together, these results suggest that exposure to developmental exposure to environmentally relevant levels of xenoestrogens may negatively impact bone length and strength in adulthood.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Benzhydryl Compounds
  • Biomechanical Phenomena
  • Collagen / metabolism
  • Diethylstilbestrol / administration & dosage
  • Diethylstilbestrol / pharmacology*
  • Dose-Response Relationship, Drug
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / pharmacology*
  • Female
  • Femur / anatomy & histology*
  • Femur / drug effects
  • Femur / embryology*
  • Fetal Development / drug effects*
  • Injections, Subcutaneous
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Phenols / administration & dosage
  • Phenols / pharmacology*
  • Pregnancy
  • Tensile Strength / drug effects*

Substances

  • Benzhydryl Compounds
  • Phenols
  • Ethinyl Estradiol
  • Diethylstilbestrol
  • Collagen
  • bisphenol A