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Fetal and Neonatal Exposure to the Endocrine Disruptor, Methoxychlor, Reduces Lean Body Mass and Bone Mineral Density and Increases Cortical Porosity

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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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Acknowledgments

We wish to thank Dr. LC Pop for reviewing this manuscript, Dr. Schlussel for her statistical advice, AE Armenti for assisting with the in vivo experimental procedures in this study, and E Bandali for her assistance with the bone images. This study is supported by NJAES (0153866) to SAS and NIH Grant (ES013854) to MU.

Conflict of interest

Heather S. Fagnant, Mehmet Uzumcu, Patricia Buckendahl, Michael G. Dunn, Peter Shupper and Sue A. Shapses declare no conflict of interest.

Human and Animal Rights and Informed Consent

The procedures in this study were approved and conducted in accordance with the guidelines of the Rutgers University Institutional Animal Care and Use Committee.

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Authors and Affiliations

  1. Department of Nutritional Sciences, Rutgers University, 96 Lipman Drive, New Brunswick, NJ, 08901, USA

    Heather S. Fagnant, Peter Shupper & Sue A. Shapses

  2. Department of Animal Sciences, Rutgers University, New Brunswick, NJ, USA

    Mehmet Uzumcu

  3. Center for Alcohol Studies, Rutgers University, New Brunswick, NJ, USA

    Patricia Buckendahl & Michael G. Dunn

  4. Orthopaedic Research Laboratories, Robert Wood Johnson Medical School-Rutgers University, New Brunswick, NJ, USA

    Heather S. Fagnant, Mehmet Uzumcu, Patricia Buckendahl, Michael G. Dunn, Peter Shupper & Sue A. Shapses

Authors
  1. Heather S. Fagnant
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  2. Mehmet Uzumcu
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  3. Patricia Buckendahl
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Correspondence to Sue A. Shapses.

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Fagnant, H.S., Uzumcu, M., Buckendahl, P. et al. Fetal and Neonatal Exposure to the Endocrine Disruptor, Methoxychlor, Reduces Lean Body Mass and Bone Mineral Density and Increases Cortical Porosity. Calcif Tissue Int 95, 521–529 (2014). https://doi.org/10.1007/s00223-014-9916-x

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  • DOI: https://doi.org/10.1007/s00223-014-9916-x

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