Abstract |
Endogenous estrogen has beneficial effects on mature bone and negatively affects the developing skeleton, whereas the effect of environmental estrogens is not known. Methoxychlor (MXC) is a synthetic estrogen known as a persistent organochlorine and used as a pesticide. Methoxychlor and its metabolites display estrogenic, anti-estrogenic and anti-androgenic activity and may therefore influence bone. Fifty-eight male fetal and neonatal rats were exposed to either: a negative control ( DMSO), 0.020, 100 mg/kg MXC, or 1 mg/kg β-estradiol-3-benzoate (EB; positive control). Rats were treated daily for 11 days, from embryonic day 19 to postnatal day (PND) 7 or for 4 days during the postnatal period (PND 0-7). All rats were analyzed at PND-84. Total body, femur, spine, and tibia areal bone mineral density (BMD) and content (BMC), lean body mass (LBM) and fat were measured by dual energy X-ray absorptiometry. Bone geometry and volumetric (v) BMD were measured using micro-computed tomography and biomechanical properties using three-point bending were assessed. Rats exposed to EB or MXC (at either the high and/or low dose), independent of exposure interval showed lower body weight, LBM, tibia and femur BMD and length, and total body BMD and BMC than DMSO control group (p ≤ 0.05). Methoxychlor and EB exposure increased cortical porosity compared to DMSO controls. Trabecular vBMD, number and separation, and cortical polar moment of inertia and cross-sectional area were lower due to EB exposure compared to control (p < 0.05). Early MXC exposure compromises cortical porosity and bone size at maturity, and could ultimately increase the risk of fracture with aging.
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Authors | Heather S Fagnant, Mehmet Uzumcu, Patricia Buckendahl, Michael G Dunn, Peter Shupper, Sue A Shapses |
Journal | Calcified tissue international
(Calcif Tissue Int)
Vol. 95
Issue 6
Pg. 521-9
(Dec 2014)
ISSN: 1432-0827 [Electronic] United States |
PMID | 25326143
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Insecticides
- Methoxychlor
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Topics |
- Absorptiometry, Photon
- Animals
- Animals, Newborn
- Body Composition
(drug effects)
- Bone Density
(drug effects)
- Bone and Bones
(drug effects)
- Female
- Fetus
- Insecticides
(toxicity)
- Male
- Methoxychlor
(toxicity)
- Pregnancy
- Prenatal Exposure Delayed Effects
(pathology)
- Rats
- Rats, Inbred F344
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