School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Anhui Medical University, Hefei, 230601, China.
Arch Toxicol. 2023 Nov;97(11):2929-2941. doi: 10.1007/s00204-023-03584-3. Epub 2023 Aug 21.
Maternal lipopolysaccharide (LPS) exposure during pregnancy has been related to IUGR. Here, we explored whether paternal LPS exposure before mating impaired fetal development. All male mice except controls were intraperitoneally injected with LPS every other day for a total of five injections. The next day after the last LPS, male mice were mated with untreated female mice. Interestingly, fetal weight and crown-rump length were reduced, while the incidence of IUGR was increased in paternal LPS exposure group. Additionally, paternal LPS exposure leaded to poor placental development through causing cell proliferation inhibition and apoptosis. Additional experiment demonstrated that the inactivation of placental PI3K/AKT pathway might be involved in paternal LPS-induced cell proliferation inhibition and apoptosis of trophoblast cells. Furthermore, the mRNA and protein levels of mesoderm specific transcript (MEST), a maternally imprinted gene with paternal expression, were significantly decreased in mouse placentas from paternal LPS exposure. Further analysis showed that paternal LPS exposure caused the inactivation of placental PI3K/AKT pathway and then cell proliferation inhibition and apoptosis might be via down-regulating placental MEST. Overall, our results provide evidence that paternal LPS exposure causes poor placental development and subsequently IUGR may be via down-regulating MEST/PI3K/AKT pathway, and then inducing cell proliferation inhibition and apoptosis in placentas.
母体脂多糖（LPS）暴露与宫内发育迟缓（IUGR）有关。在这里，我们探讨了父体 LPS 暴露是否会在交配前损害胎儿发育。除对照组外，所有雄性小鼠每隔一天腹膜内注射 LPS 共 5 次。最后一次 LPS 注射后的第二天，雄性小鼠与未经处理的雌性小鼠交配。有趣的是，父体 LPS 暴露组的胎儿体重和头臀长降低，而 IUGR 的发生率增加。此外，父体 LPS 暴露通过抑制细胞增殖和诱导细胞凋亡导致胎盘发育不良。进一步的实验表明，胎盘 PI3K/AKT 通路的失活可能参与了父体 LPS 诱导的滋养细胞增殖抑制和凋亡。此外，胎盘中母体印迹基因父系表达的中胚层特异性转录物（MEST）的 mRNA 和蛋白水平在父体 LPS 暴露的小鼠胎盘组织中明显降低。进一步分析表明，父体 LPS 暴露导致胎盘 PI3K/AKT 通路失活，从而通过下调胎盘 MEST 引起细胞增殖抑制和凋亡。总体而言，我们的研究结果提供了证据，表明父体 LPS 暴露导致胎盘发育不良，进而 IUGR 可能通过下调 MEST/PI3K/AKT 通路，然后诱导胎盘细胞增殖抑制和凋亡。
