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双酚 A 通过改变基因表达影响青春期小鼠的卵巢发育。

Bisphenol A affects ovarian development in adolescent mice caused by genes expression change.

机构信息

Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation, Anhui Province Key Laboratory of Environmental Hormone and Reproduction, Fuyang Normal University, Fuyang, China.

Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation, Anhui Province Key Laboratory of Environmental Hormone and Reproduction, Fuyang Normal University, Fuyang, China.

出版信息

Gene. 2020 May 25;740:144535. doi: 10.1016/j.gene.2020.144535. Epub 2020 Mar 7.

Abstract

Many human epidemiology and animal model studies have reported that bisphenol A (BPA) exerts adverse effects on reproduction through different regulatory mechanisms and signaling pathways in adults. In recent years, the exposure risk has increased for the general population, and little is known about how BPA affects ovarian development in adolescent animals and humans. In the present study, we aimed to investigate the effects of BPA exposure on ovarian development and the transcriptome in adolescent mice. Four-week-old ICR female mice were randomly divided into two groups and orally administered BPA (200 ng/kg/day) by gavage for 4 weeks. The BPA and estrogen (E2) levels in sera from the two groups were subsequently determined by using enzyme-linked immunosorbent assays (ELISAs). An immunohistochemical study showed that several obvious ovarian structural and developmental abnormalities were observed in the treatment group with changes in the E2 receptor gene and protein expression levels. A total of 4266 differentially expressed genes (DEGs) were identified, and the possible functions of these DEGs were explored by bioinformatics analyses based on the RNA-Seq data. The two most significant expression profiles were identified by Short Time-series Expression Miner (STEM) software, and the genes in these two profiles were enriched in actin filament-based processes, behaviour and membrane potential regulation according to Gene Ontology (GO) enrichment analysis. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEGs are particularly involved in the endocrine system, the calcium and cAMP signaling pathways.

摘要

许多人类流行病学和动物模型研究报告称,双酚 A(BPA)通过不同的调节机制和信号通路对成年动物的生殖系统产生不良影响。近年来,由于普通人群的暴露风险增加,人们对 BPA 如何影响青少年动物和人类的卵巢发育知之甚少。在本研究中,我们旨在研究 BPA 暴露对青春期小鼠卵巢发育和转录组的影响。将 4 周龄 ICR 雌性小鼠随机分为两组,通过灌胃分别给予 BPA(200ng/kg/天)连续 4 周。随后通过酶联免疫吸附试验(ELISA)测定两组血清中的 BPA 和雌二醇(E2)水平。免疫组织化学研究表明,治疗组观察到几种明显的卵巢结构和发育异常,E2 受体基因和蛋白表达水平发生改变。通过 RNA-Seq 数据的生物信息学分析,共鉴定出 4266 个差异表达基因(DEGs),并探讨了这些 DEGs 的可能功能。通过短时间序列表达挖掘器(STEM)软件鉴定出两个最显著的表达谱,这两个表达谱中的基因根据基因本体论(GO)富集分析,富集在肌动蛋白丝为基础的过程、行为和膜电位调节中。此外,京都基因与基因组百科全书(KEGG)通路分析表明,这些 DEGs 特别参与内分泌系统、钙和 cAMP 信号通路。

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