Fetal and neonatal exposure to the endocrine disruptor, methoxychlor, reduces lean body mass and bone mineral density and increases cortical porosity
Autor: | Heather S. Fagnant, Patricia Buckendahl, Peter Shupper, Michael G. Dunn, Sue A. Shapses, Mehmet Uzumcu |
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Rok vydání: | 2014 |
Předmět: |
musculoskeletal diseases
Male medicine.medical_specialty Insecticides medicine.drug_class Endocrinology Diabetes and Metabolism Bone and Bones chemistry.chemical_compound Endocrinology Absorptiometry Photon Fetus Bone Density Pregnancy Internal medicine medicine Animals Orthopedics and Sports Medicine Femur Tibia Bone mineral Methoxychlor Skeleton (computer programming) Rats Inbred F344 Rats chemistry Endocrine disruptor Animals Newborn Estrogen Prenatal Exposure Delayed Effects Lean body mass Body Composition Female |
Zdroj: | Calcified tissue international. 95(6) |
ISSN: | 1432-0827 |
Popis: | 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. |
Databáze: | OpenAIRE |
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