Changes in gene expression following long-term in vitro exposure of Macaca mulatta trophoblast stem cells to biologically relevant levels of endocrine disruptors

Trophoblast stem cells (TSCs) are key for embryo implantation and placentation. Environmental toxicants that compromise trophoblast function could compromise fetal viability, pregnancy outcome, and progeny health. Endocrine disrupting chemicals (EDCs) can epigenetically modify cells and alter their developmental properties. Understanding the effects of low, chronic EDC exposures on TSCs and pregnancy is a priority in developmental toxicology. Differences in placentation between primates and other mammals make a nonhuman primate model ideal for this. We examined effects of chronic low-level exposure to five EDCs on rhesus monkey TSCs in vitro. Two of the toxicants, ATR and TBT, exerted the strongest effects, with substantial overlap. Affected genes included some with obvious relevance to placentation and implantation (WNT7A, INHBA, and cytokines and their receptors). Pathway analysis revealed significant reductions in the expression of genes related to cytokine signaling, a feature shared across all five EDCs tested. Low-level chronic exposure of primate TSCs to EDCs may thus compromise trophoblast development in vivo, modify responses to pathogens and other challenges, and negatively affect embryo implantation and pregnancy rate. Effects of chronic exposure to low concentrations of 5 EDCs were tested in rhesus monkey trophoblast stem cells