Differential Changes in Akt and AMPK Phosphorylation Regulating mTOR Activity in the Placentas of Pregnancies Complicated by Fetal Growth Restriction and Gestational Diabetes Mellitus With Large-For-Gestational Age Infants

作者：Tai‐Ho Hung, Chung‐Pu Wu, Szu‐Fu Chen · 发表于：Frontiers in Medicine · 年份：2021 · DOI：10.3389/fmed.2021.788969 · 被引用次数：26 · 研究领域：Pregnancy and preeclampsia studies、Birth, Development, and Health、Genetic Syndromes and Imprinting

Background: Dysregulation of placental mechanistic target of rapamycin (mTOR) activity has been implicated in the pathophysiology of pregnancies complicated by idiopathic fetal growth restriction (FGR) and gestational diabetes mellitus (GDM) with large-for-gestational-age (LGA) infants. However, the underlying mechanisms remain unclear. Methods: We obtained placentas from women with normal pregnancies ( n = 11) and pregnancies complicated by FGR ( n = 12) or GDM with LGA infants ( n = 12) to compare the levels of total and phosphorylated forms of Akt, AMPK, TSC2, and mTOR among the three groups and used primary cytotrophoblast cells isolated from 30 normal term placentas to study the effects of oxygen–glucose deprivation (OGD) and increasing glucose concentrations on the changes of these factors in vitro . Results: Placentas from FGR pregnancies had lower phosphorylated Akt (p-Akt) levels ( P &lt; 0.05), higher p-AMPKα levels ( P &lt; 0.01), and lower mTOR phosphorylation ( P &lt; 0.05) compared to that of normal pregnant women. Conversely, women with GDM and LGA infants had higher p-Akt ( P &lt; 0.001), lower p-AMPKα ( P &lt; 0.05), and higher p-mTOR levels ( P &lt; 0.05) in the placentas than normal pregnant women. Furthermore, primary cytotrophoblast cells subjected to OGD had lower p-Akt and p-mTOR (both P &lt; 0.05) and higher p-AMPKα levels ( P &lt; 0.05) than those cultured under standard conditions, but increasing glucose concentrations...