Nutrient sensor signaling pathways and cellular stress in fetal growth restriction.
Nutrient sensor signaling pathways and cellular stress in fetal growth restriction.
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DOI：
10.1530/jme-18-0059
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发表时间：
2019-02-01
影响因子：
3.5
通讯作者：
Alejandro EU
中科院分区：
文献类型：
--
作者：
Hart B;Morgan E;Alejandro EU
胎儿生长受限是最常见的产科并发症之一，会导致严重的围产期发病和死亡。人类单胎胎儿生长受限最常见的病因是胎盘功能不全，其继发于子宫 - 胎盘灌注减少、胎盘形成异常、滋养细胞侵袭和螺旋动脉重塑受损，进而导致营养物质和氧气转运改变。参与胎盘发育以及葡萄糖和氨基酸转运的两种营养感知蛋白是雷帕霉素靶蛋白（mTOR）和O - 连接N - 乙酰葡糖胺转移酶（OGT），它们均受氧气可利用度的调节。这些通路中任何一条受损都与胎儿生长受限相关，同时胎盘会出现缺氧、氧化应激、内质网（ER）应激、代谢功能障碍和营养缺乏等形式的细胞应激。最近有证据表明营养传感器对胎儿应激反应可能存在影响，且这种影响存在性别差异，这表明胎儿生长受限可能存在遗传性别易感性因素。在这篇小型综述中，我们聚焦于mTOR和OGT在人类胎儿生长受限中胎盘发育、营养调节及细胞应激反应方面的已知作用，并辅以来自啮齿动物模型的证据。
Fetal growth restriction is one of the most common obstetrical complications resulting in significant perinatal morbidity and mortality. The most frequent etiology of human singleton fetal growth restriction is placental insufficiency, which occurs secondary to reduced utero-placental perfusion, abnormal placentation, impaired trophoblast invasion and spiral artery remodeling, resulting in altered nutrient and oxygen transport. Two nutrient-sensing proteins involved in placental development and glucose and amino acid transport are mechanistic target of rapamycin (mTOR) and O-linked N-acetylglucosamine transferase (OGT), which are both regulated by availability of oxygen. Impairment in either of these pathways is associated with fetal growth restriction and accompanied by cellular stress in the forms of hypoxia, oxidative and endoplasmic reticulum (ER) stress, metabolic dysfunction and nutrient starvation in the placenta. Recent evidence has emerged regarding the potential impact of nutrient sensors on fetal stress response, which occurs in a sexual dysmorphic manner, indicating a potential element of genetic gender susceptibility to fetal growth restriction. In this mini review, we focus on the known role of mTOR and OGT in placental development, nutrient regulation and response to cellular stress in human fetal growth restriction with supporting evidence from rodent models.