A multi-generational study on low-dose BPA exposure in Wistar rats: Effects on maternal behavior, flavor intake and development
A multi-generational study on low-dose BPA exposure in Wistar rats: Effects on maternal behavior, flavor intake and development
复制标题
DOI：
10.1016/j.ntt.2013.11.002
复制
发表时间：
2014-01-01
影响因子：
2.9
通讯作者：
Canivenc-Lavier, Marie-Chantal
中科院分区：
文献类型：
--
作者：
Boudalia, Sofiane;Berges, Raymond;Canivenc-Lavier, Marie-Chantal
双酚A（BPA）是一种常见的内分泌干扰物，是一种环境和食品污染物。它对发育和行为都有影响，主要是在生命早期接触时。本研究的目的是确定慢性、人类相关的低剂量BPA暴露对Wistar大鼠发育、母体行为和口味偏好的多代效应。从妊娠第一天（GD 1）至哺乳期最后一天（LD 21），以5 μ g/kg体重的日剂量经口给予FO妊娠母鼠BPA，然后从断奶（PND 21）到成年（PND 100）的F1后代。F2代子代未暴露。每天评估毒性的发展和临床体征。通过观察从分娩到LD 8的FO和Fl母鼠的哺乳和幼鼠护理行为以及“非母性”行为来评价母性行为。在PND 21-34和PND 86- 99时，使用双瓶选择测试，基于甜味、咸味和脂肪溶液的摄入量评估F1和F2后代的风味偏好。BPA暴露：1）F1母鼠的母性行为减少，2）在F1和F2后代中引起发育缺陷，雄性大鼠的肛门生殖器距离明显减少，3）不影响F1代调味溶液的摄入量，但引起F2代幼鱼对甜味的偏好和F2代成年鱼对盐和脂肪溶液的摄入量的变化，4）仅引起F2代体重增加，而摄食量和饮水量没有变化。我们的研究结果表明，妊娠期（F0）和终身（F1）暴露于人体相关剂量的BPA可诱导对发育和行为的多代影响。这些结果表明，BPA暴露可能导致选择性神经内分泌缺陷和/或表观遗传变化。(c)2013 Elsevier Inc. All rights reserved.
Bisphenol A (BPA) is a common endocrine disruptor found as an environmental and food contaminant. It exerts both developmental and behavioral effects, mainly when exposure occurs in early life. The aim of this study was to determine the multi-generational effects of chronic, human-relevant low-dose exposure to BPA on development, maternal behavior and flavor preference in Wistar rats.BPA was orally administered at a daily dose of 5 mu g/kg body weight to FO pregnant dams from the first day of gestation (GD 1) until the last day of lactation (LD 21), and then to Fl offspring from weaning (PND 21) to adulthood (PND 100). F2 offspring were not exposed. Development and clinical signs of toxicity were assessed daily. Maternal behavior was evaluated by observing nursing and pup-caring actions, as well as "non-maternal" behaviors in FO and Fl dams from parturition until LD 8. The flavor preferences of Fl and F2 offspring were evaluated based on the intake of sweet, salt and fat solutions using the two-bottle choice test on PND 21-34 and PND 86-99.BPA exposure: 1) decreased maternal behavior in Fl dams, 2) caused developmental defects in both Fl and F2 offspring, with a noticeable decrease in anogenital distance in male rats, and 3) did not affect flavored solution intake in Fl, but induced changes in sweet preference in F2 juveniles and in salt and fat solution intakes in F2 adults, and 4) induced a body weight increase in the F2 generation only, whereas food intake and water consumption did not change.Taken as a whole, our findings showed that both gestational (F0) and lifelong (F1) exposures to a human-relevant dose of BPA could induce multi-generational effects on both development and behavior. These results suggest possible selective neuroendocrine defects and/or epigenetic changes caused by BPA exposure. (c) 2013 Elsevier Inc. All rights reserved.