Multigenerational study of the obesogen effects of bisphenol S after a perinatal exposure in C57BL6/J mice fed a high fat diet
Multigenerational study of the obesogen effects of bisphenol S after a perinatal exposure in C57BL6/J mice fed a high fat diet
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DOI：
10.1016/j.envpol.2020.116243
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发表时间：
2021-02-01
影响因子：
8.9
通讯作者：
Chagnon, Marie-Christine
中科院分区：
文献类型：
--
作者：
Brulport, Axelle;Le Corre, Ludovic;Chagnon, Marie-Christine
背景：双酚S是一种内分泌干扰物，表现出代谢紊乱，尤其是在围产期暴露后。目的：研究BPS对雄性和雌性小鼠体重、脂肪组织和血浆参数的影响。方法：从妊娠第0天至出生后第21天，通过饮用BPS(1.5 mg/kg bw/d，相当于0.12 mg/kg bw/d)，观察BPS对C57BL6/J小鼠的致肥胖作用。在15周的时间里，所有的子代都用高脂饲料喂养。安乐死前每周监测体重并测量脂肪量。在安乐死时，测定血糖、胰岛素、甘油三酯、胆固醇和NO酯化脂肪酸的血浆水平，并检测内脏脂肪组织中的基因表达。雄性和雌性F1交配，得到F2代。同样，对F2代小鼠进行杂交，以获得F3代。结果：在F1中，BPS诱导了与脂解基因表达上调相关的雄性小鼠超重。在F1女性中，观察到血脂异常。在F2，男性和女性的BPS暴露与体重、脂肪和增值税质量的增加有关。一些血浆参数有所增加，但与性别有关(男性的血糖、甘油三酯和胆固醇，女性的NEFA)。我们观察到参与脂肪生成和脂肪分解的基因在女性中表达下调，但在男性中仅在脂肪生成中下调。在F3，VAT质量下降和脂肪生成基因表达上调仅在女性中发生。结论：围产期BPS暴露诱导了性别依赖性肥胖原多代效应，其中F2代受影响最大。跨代干扰只在女性身上持续存在。(C)2020爱思唯尔有限公司。保留所有权利。
Background: Bisphenol S is an endocrine disruptor exhibiting metabolic disturbances, especially following perinatal exposures. To date, no data are available on the obesogen effects of BPS in a mutligenerational issue.Objectives: We investigated obesogen effects of BPS in a multigenerational study by focusing on body weight, adipose tissue and plasma parameters in male and female mice.Methods: Pregnant C57BL6/J mice were exposed to BPS (1.5 mg/kg bw/day ie a human equivalent dose of 0.12 mg/kg bw/day) by drinking water from gestational day 0 to post natal day 21. All offsprings were fed with a high fat diet during 15 weeks. Body weight was monitored weekly and fat mass was measured before euthanasia. At euthanasia, blood glucose, insuline, triglyceride, cholesterol and no esterified fatty acid plasma levels were determined and gene expressions in visceral adipose tissue were assessed. F1 males and females were mated to obtain the F2 generation. Likewise, the F2 mice were cross-bred to obtain F3. The same analyses were performed.Results: In F1 BPS induced an overweight in male mice associated to lipolysis gene expressions upregulation. In F1 females, dyslipidemia was observed. In F2, BPS exposure was associated to an increase in body weight, fat and VAT masses in males and females. Several plasma parameters were increased but with a sex related pattern (blood glucose, triglycerides and cholesterol in males and NEFA in females). We observed a down-regulation in mRNA expression of gene involved in lipogenesis and in lipolysis for females but only in the lipogenesis for males. In F3, a decrease in VAT mass and an upregulation of lipogenesis gene expression occurred only in females.Conclusions: BPS perinatal exposure induced sex-dependent obesogen multigenerational effects, the F2 generation being the most impacted. Transgenerational disturbances persisted only in females. (C) 2020 Elsevier Ltd. All rights reserved.