Department of Physiology, Basic Medical College, Nanchang University, Nanchang, Jiangxi, 330006, PR China.
Jiangxi Provincial Key Laboratory of Reproductive Physiology and Pathology, Medical Experimental Teaching Center, Nanchang University, Nanchang, Jiangxi, 330006, PR China.
J Hazard Mater. 2019 Apr 5;367:160-170. doi: 10.1016/j.jhazmat.2018.12.061. Epub 2018 Dec 18.
Acrylamide, a carcinogen and neurotoxic substance, recently has been discovered in various heat-treated carbohydrate-rich foods. The aim of this study was to investigate the effects of acrylamide exposure on placental development. Pregnant mice received acrylamide by gavage at dosages of 0, 10, and 50 mg/kg/day from gestational days (GD) 3 until GD 8 or GD 13. The results showed that acrylamide feeding significantly decreased the numbers of viable embryos and increased the numbers of resorbed embryos on GD 13. Acrylamide exposure reduced the absolute and relative weight of placentas and embryos, and inhibited the development of ectoplacental cone (EPC) and placenta, as shown by the atrophy of EPC and reduced placental area. Acrylamide markedly reduced the numbers of labyrinth vessels. Expression levels of most placental key genes such as Esx1, Hand1, and Hand2 mRNA dramatically decreased in acrylamide-treated placentas. Furthermore, acrylamide treatment inhibited proliferation and induced apoptosis of placentas, as shown by decreased Ki67-positive cells and Bcl-2 protein, and increased the expression of Bax, cleaved-caspase-3, and cleaved-caspase-8 proteins. In conclusion, our results indicated that gestational exposure to acrylamide inhibits placental development through dysregulation of placental key gene expression and labyrinth vessels, suppression of proliferation, and apoptosis induction in mice.
丙烯酰胺是一种致癌物质和神经毒性物质,最近在各种经过热处理的富含碳水化合物的食物中被发现。本研究旨在探讨丙烯酰胺暴露对胎盘发育的影响。怀孕的小鼠从妊娠第 3 天到第 8 天或第 13 天通过灌胃接受 0、10 和 50mg/kg/天的丙烯酰胺。结果表明,丙烯酰胺喂养显著降低了活胚胎的数量,并增加了 GD13 时吸收胚胎的数量。丙烯酰胺暴露降低了胎盘和胚胎的绝对和相对重量,并抑制了胎盘外腔(EPC)和胎盘的发育,表现为 EPC 萎缩和胎盘面积减少。丙烯酰胺明显减少了绒毛血管的数量。在丙烯酰胺处理的胎盘中,大多数胎盘关键基因如 Esx1、Hand1 和 Hand2 的表达水平显著降低。此外,丙烯酰胺处理抑制了胎盘的增殖并诱导其凋亡,表现为 Ki67 阳性细胞和 Bcl-2 蛋白减少,Bax、裂解 caspase-3 和裂解 caspase-8 蛋白表达增加。总之,我们的结果表明,妊娠期间暴露于丙烯酰胺通过调节胎盘关键基因表达和绒毛血管、抑制增殖和诱导凋亡来抑制小鼠的胎盘发育。