Fetal and neonatal exposure to the endocrine disruptor, methoxychlor, reduces lean body mass and bone mineral density and increases cortical porosity.
Fetal and neonatal exposure to the endocrine disruptor, methoxychlor, reduces lean body mass and bone mineral density and increases cortical porosity.
复制标题
胎儿和新生儿接触内分泌干扰物甲氧滴滴涕会降低去脂体重和骨矿物质密度，并增加皮质孔隙度。
DOI：
10.1007/s00223-014-9916-x
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发表时间：
2014
影响因子：
4.2
通讯作者：
Shapses,SueA
中科院分区：
文献类型：
--
作者：
Fagnant,HeatherS;Uzumcu,Mehmet;Buckendahl,Patricia;Dunn,MichaelG;Shupper,Peter;Shapses,SueA
内源性雌激素对成熟骨有有益作用，对发育中的骨骼有负面影响，而环境雌激素的作用尚不清楚。甲氧基氯（MXC）是一种合成雌激素，被称为持久性有机氯，用作杀虫剂。甲氧基氯及其代谢物显示雌激素、抗雌激素和抗雄激素活性，因此可能影响骨骼。58只雄性胎鼠和新生大鼠分别暴露于阴性对照（DMSO）、0.020、100 mg/kg MXC或1 mg/kg β-雌二醇-3-苯甲酸酯（EB；阳性对照）。从胚胎第19天至产后第7天（PND），每天给药11天，或产后第4天（PND 0-7）。所有大鼠在PND-84进行分析。采用双能x线骨密度仪测量全身、股骨、脊柱和胫骨的骨矿物质密度（BMD）和含量（BMC）、瘦体质量（LBM）和脂肪。使用显微计算机断层扫描测量骨几何和体积(v) BMD，并使用三点弯曲评估生物力学特性。大鼠暴露于EB或MXC（高剂量和/或低剂量），无论暴露间隔如何，其体重、LBM、胫骨和股骨骨密度和长度以及全身骨密度和BMC均低于DMSO对照组（p≤0.05）。与DMSO对照相比，甲氧基氯和EB暴露增加了皮质孔隙度。与对照组相比，EB暴露降低了小梁vBMD、小梁数量、小梁间距、小梁皮质极惯性矩和横截面积（p< 0.05）。早期暴露于MXC会损害成熟时的皮质孔隙度和骨大小，并最终增加随年龄增长而骨折的风险。
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.