Single-cell transcriptomic profiling to evaluate the effects of Di(2-ethylhexyl)phthalate exposure on early meiosis of female mouse germ cells.
Single-cell transcriptomic profiling to evaluate the effects of Di(2-ethylhexyl)phthalate exposure on early meiosis of female mouse germ cells.
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DOI：
10.1016/j.chemosphere.2022.135698
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发表时间：
2022-07
期刊：
影响因子：
8.8
通讯作者：
Yu Tian;Ye Zhang;Pei Dong;Yong-hong Sun;Ai-Hong Zhao;W. Shen;Xi-Feng Zhang
中科院分区：
文献类型：
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作者：
Yu Tian;Ye Zhang;Pei Dong;Yong-hong Sun;Ai-Hong Zhao;W. Shen;Xi-Feng Zhang
邻苯二甲酸二(2-乙基己基)酯(DEHP)具有内分泌干扰物(EDC)的特性，可威胁人类和其他动物的生殖健康。在哺乳动物中，一系列的染色体事件发生在卵母细胞的减数分裂阶段。外来毒素可能会进入人体，导致不孕不育和其他相关疾病。因此，探讨DEHP暴露对生殖细胞减数分裂分子机制的影响具有重要意义。我们使用单细胞RNA测序技术(scRNA-seq)分析了孕鼠暴露DEHP后12.5天(E12.5天)和14.5天(E14.5天)胎鼠的卵巢。DEHP暴露进一步激活了生殖细胞中与DNA修复相关的通路，增加了与DNA损伤相关的基因表达，改变了生殖细胞的发育轨迹。DEHP可影响颗粒前(PG)细胞的增殖。此外，DEHP暴露改变了PG细胞和生殖细胞之间的信号转导。我们发现DEHP通过引起卵母细胞DNA损伤和破坏PG细胞和生殖细胞之间的信号转导来影响减数分裂。这些结果为DEHP介导的女性生殖健康问题的防治提供了有力的理论依据。
Di(2-ethylhexyl)phthalate (DEHP) has proven characteristics of an endocrine-disrupting compound (EDC), which can threaten the reproductive health of humans and other animals. In mammals, a series of chromosomal events occur during the meiotic stage of oocytes. External toxins may enter the body and cause infertility and other related diseases. Therefore, it is crucial to explore the influence of DEHP exposure on the molecular mechanism of germ cell meiosis. We used single-cell RNA sequencing (scRNA-seq) to analyse the ovaries of foetal mice at embryonic day 12.5 (E12.5) and E14.5 after maternal DEHP exposure. DEHP exposure further activated the pathways related to DNA repair in germ cells, increased the expression of genes related to DNA damage and changed the developmental trajectory of germ cells. DEHP exposure may affect the proliferation of pregranulosa (PG) cells. Moreover, DEHP exposure altered the signal transduction between PG cells and germ cells. We showed that DEHP affects meiosis by causing DNA damage in oocytes and disrupting the signal transduction between PG cells and germ cells. These results provide a strong theoretical basis for the prevention and treatment of DEHP-mediated female reproductive health problems.