Suppr超能文献

母体暴露于邻苯二甲酸二(2-乙基己基)酯(DEHP)会通过雌性生殖系促进成年期生殖功能障碍在小鼠中的跨代遗传。

Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice.

作者信息

Pocar Paola, Fiandanese Nadia, Berrini Anna, Secchi Camillo, Borromeo Vitaliano

机构信息

Department of Veterinary Medicine, University of Milan, 20133 Milan, Italy.

Department of Veterinary Medicine, University of Milan, 20133 Milan, Italy.

出版信息

Toxicol Appl Pharmacol. 2017 May 1;322:113-121. doi: 10.1016/j.taap.2017.03.008. Epub 2017 Mar 9.

Abstract

Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant.

摘要

内分泌干扰物(EDs)是一类已知的化合物,在胎儿性腺发育期间母体暴露后,可促进成年期疾病在后代中的跨代遗传。本研究旨在确定在小鼠中,孕期和哺乳期以环境剂量暴露于增塑剂邻苯二甲酸二(2-乙基己基)酯(DEHP)是否会对成年雌性后代三代的生殖健康产生跨代影响。从妊娠第0.5天到哺乳期结束,妊娠的F0代母鼠在饮食中分别暴露于0、0.05、5mg/kg/天的DEHP。记录F1、F2和F3代雌性后代生殖功能中成年期疾病的发病率。在成年F1代雌性中,DEHP暴露导致了生殖方面的不良反应,包括:i)卵巢卵泡动态改变,原始卵泡储备减少,生长中的前窦卵泡群体增大,提示卵泡募集加速;ii)卵母细胞质量和胚胎发育能力下降;iii)一组选定的卵巢和植入前胚胎基因的表达谱失调。F2和F3代雌性后代表现出与F1代相同的生殖形态表型改变和基因表达谱,从而显示出雌性谱系中生殖不良反应的跨代传递。这些发现表明,在小鼠中,在性腺性别决定期间暴露于与人类暴露相关剂量的DEHP会显著扰乱成年雌性后代及其后代的生殖指标。跨代传递的证据对动物和人类的生殖健康和生育能力具有重要意义,显著增加了这种有毒物质的潜在生物危害。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验