Department of Animal Science, Department of Obstetrics, Gynecology and Reproductive Biology, Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, MI 48824, United States.
California National Primate Research Center and Department of Obstetrics and Gynecology, University of California, Davis, CA 95616, United States.
Reprod Toxicol. 2018 Apr;77:154-165. doi: 10.1016/j.reprotox.2018.02.012. Epub 2018 Mar 2.
Trophoblast stem cells (TSCs) are crucial for embryo implantation and placentation. Environmental toxicants that compromise TSC function could impact fetal viability, pregnancy, and progeny health. Understanding the effects of low, chronic EDC exposures on TSCs and pregnancy is a priority in developmental toxicology. Differences in early implantation between primates and other mammals make a nonhuman primate model ideal. We examined effects of chronic low-level exposure to atrazine, tributyltin, bisphenol A, bis(2-ethylhexyl) phthalate, and perfluorooctanoic acid on rhesus monkey TSCs in vitro by RNA sequencing. Pathway analysis of affected genes revealed negative effects on cytokine signaling related to anti-viral response, most strongly for atrazine and tributyltin, but shared with the other three EDCs. Other affected processes included metabolism, DNA repair, and cell migration. Low-level chronic exposure of primate TSCs to EDCs may thus compromise trophoblast development in vivo, inhibit responses to infection, and negatively affect embryo implantation and pregnancy.
滋养层干细胞（TSC）对于胚胎着床和胎盘形成至关重要。影响 TSC 功能的环境毒素可能会影响胎儿的存活、妊娠和后代的健康。了解低水平、慢性环境内分泌干扰物对 TSC 和妊娠的影响是发育毒理学的优先事项。灵长类动物和其他哺乳动物在早期着床方面的差异使得非人类灵长类动物模型成为理想选择。我们通过 RNA 测序研究了慢性低水平暴露于莠去津、三丁基锡、双酚 A、邻苯二甲酸二（2-乙基己基）酯和全氟辛酸对食蟹猴 TSC 的影响。受影响基因的途径分析显示，它们对与抗病毒反应相关的细胞因子信号通路产生负面影响，其中莠去津和三丁基锡的影响最为强烈，但与其他三种环境内分泌干扰物也存在共同影响。其他受影响的过程包括代谢、DNA 修复和细胞迁移。因此，低水平慢性暴露于 EDCS 可能会损害体内滋养层的发育，抑制对感染的反应，并对胚胎着床和妊娠产生负面影响。
