辅助生殖技术（ART）致胎盘发育和功能异常，是导致新生儿不良妊娠结局及胚胎源性疾病发生风险增加的重要原因。但ART致胎盘异常的机制亟待阐明。本课题组前期系统研究了ART对胎盘发育及印记基因表达的影响，发现ART致妊娠末期小鼠胎盘过度生长、糖原和脂质异常积累，印记基因Phlda2表达水平显著下调。鉴于Phlda2通过负调控Akt信号通路，调控细胞增殖及糖原和脂质合成，我们提出ART致Phlda2表达下调，Akt信号过度激活，致胎盘增生，糖脂异常积累的假说。本课题拟在前期研究基础上，首先，通过分子生物学及脂质组学技术阐明Phlda2表达异常致胎盘发育异常分子通路；其次，通过BSP和CHIP技术揭示ART致Phlda2表达异常的表观遗传机制；最后，通过激活或抑制Akt通路，探索挽救ART胎盘功能的干预策略。项目的完成将进一步揭示ART致胎盘发育异常的新机制，为临床寻找干预策略提供实验及理论依据。

The placental maldevelopment and dysfunction resulted by assisted reproductive technology (ART) is an important cause of adverse pregnancy outcomes and high risk of embryo origins of diseases in later life. However, the related mechanisms that ART resulted abnormal placentation remains to be elucidated. In our previous work, we systematically studied the effects of ART on the placenta development and expression of imprinted genes. We found that ART induced placental overgrowth, placental glycogen and lipids over accumulation, and the expression level of imprinted gene Phlda2 is significantly downregulated. With Phlda2 regulate cell proliferation, glycogenesis and lipidosis through the negative regulation of Akt signal pathway; we proposed the hypothesis that ART down-regulation of Phlda2 expression that lead to excessive activation of the Akt signal, which resulted in placental hypertrophy, excessive accumulation of glycogen and lipids in placenta. In this study, firstly, we will clarify the molecular pathway that abnormal expression of Phlda2 causes placental maldevelopment and dysfunction by using molecular biology and lipidomics technologies. Secondly, to reveal the epigenetic mechanisms that ART induced the aberrant expression of Phlda2 by using BSP and CHIP Technologies. Finally, by activating or inhibiting the Akt pathway, to explore the intervention strategy to save the ART placental function. The completion of this project will reveal new mechanisms of ART induced abnormal placental development and provide theoretical bases for the markers of early warning and intervention strategies.