TY - JOUR
T1 - Developmental exposure to xenoestrogens at low doses alters femur length and tensile strength in adult mice
AU - Pelch, Katherine E.
AU - Carleton, Stephanie M.
AU - Phillips, Charlotte L.
AU - Nagel, Susan C.
PY - 2012/3/1
Y1 - 2012/3/1
N2 - 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 (EE2) on bone geometry and torsional strength. C57BL/6 mice were exposed to DES, 0.1 lg/kg/day, BPA, 10 μg/kg/day, EE2, 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 EE2, DES, or BPA increased adult femur length. Exposure to the highest dose of EE2 did not alter femur length, resulting in a nonmonotonic dose response. Exposure to EE2 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.
AB - 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 (EE2) on bone geometry and torsional strength. C57BL/6 mice were exposed to DES, 0.1 lg/kg/day, BPA, 10 μg/kg/day, EE2, 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 EE2, DES, or BPA increased adult femur length. Exposure to the highest dose of EE2 did not alter femur length, resulting in a nonmonotonic dose response. Exposure to EE2 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.
KW - Bone
KW - Developmental origins of health and disease
KW - Endocrine disruptors
KW - Environmental contaminants and toxicants
KW - Estradiol
KW - Estradiol receptor
UR - http://www.scopus.com/inward/record.url?scp=84860621651&partnerID=8YFLogxK
U2 - 10.1095/biolreprod.111.096545
DO - 10.1095/biolreprod.111.096545
M3 - Article
C2 - 22088916
AN - SCOPUS:84860621651
SN - 0006-3363
VL - 86
JO - Biology of Reproduction
JF - Biology of Reproduction
IS - 3
M1 - 69
ER -