title: Fetal and neonatal exposure to the endocrine disruptor, methoxychlor, reduces lean body mass and bone mineral density and increases cortical porosity.
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.
authors.affiliation: Department of Nutritional Sciences, Rutgers University, 96 Lipman Drive, New Brunswick, NJ, 08901, USA.
authors.forename: Heather S
authors.initials: HS
authors.lastname: Fagnant
authors.forename: Mehmet
authors.initials: M
authors.lastname: Uzumcu
authors.forename: Patricia
authors.initials: P
authors.lastname: Buckendahl
authors.forename: Michael G
authors.initials: MG
authors.lastname: Dunn
authors.forename: Peter
authors.initials: P
authors.lastname: Shupper
authors.forename: Sue A
authors.initials: SA
authors.lastname: Shapses
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D000831:Animals, Newborn; D001823:Body Composition / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects*; D005260:Female; D005333:Fetus; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008731:Methoxychlor / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D007306:Insecticides; D008731:Methoxychlor