Identification of autophagic vacuoles and regulators of autophagy in villous trophoblast from normal term pregnancies and in fetal growth restriction
Identification of autophagic vacuoles and regulators of autophagy in villous trophoblast from normal term pregnancies and in fetal growth restriction
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DOI：
10.3109/14767058.2012.733764
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发表时间：
2013-03-01
影响因子：
1.8
通讯作者：
Heazell, Alexander E. P.
中科院分区：
文献类型：
--
作者：
Curtis, Sophie;Jones, Carolyn J. P.;Heazell, Alexander E. P.
胎儿生长受限(FGR)是一种严重的妊娠并发症，与围产儿死亡率和发病率增加有关。虽然大多数FGR病例是由胎盘功能障碍引起的，但其病理生理机制尚不完全清楚。自噬是细胞退化的一种生理形式，营养和氧气限制加剧了细胞退化，这两种因素都被认为在FGR的病因中发挥了作用。我们假设自噬存在于正常的人胎盘中，并在FGR中被夸大。在电子显微镜下观察正常胎盘和FGR胎盘的自噬情况，并通过Western blotting检测LC3B和LAMP-2的表达。免疫组织化学方法检测自噬调节因子的定位。用BeWo细胞培养法研究营养和/或缺氧是否能诱导滋养层细胞自噬。自噬主要定位于合体滋养层，自噬小体在FGR中更为常见。调节因子LAMP-2、LC3B、Beclin-1、ATG5、ATG9和ATG16L1均存在于绒毛滋养细胞。LAMP-2免疫组织化学染色在FGR中呈点状分布。在BeWo细胞中，在低氧压和/或血清耗尽的条件下培养会导致自噬小体的出现，这与LAMP-2构型的变化有关。我们得出结论，人类足月胎盘的自噬可能与FGR的胎盘功能障碍有关。
Fetal growth restriction (FGR) is a serious pregnancy complication associated with increased perinatal mortality and morbidity. Although the majority of cases with FGR result from placental dysfunction, the pathophysiology is incompletely understood. Autophagy is a physiological form of cell degradation exacerbated by nutrient and oxygen restriction, which are both thought to play a role in the aetiology of FGR. We hypothesized that autophagy is present in the normal human placenta and is exaggerated in FGR. Autophagy was assessed in electron micrographs from normal and FGR placentas and by Western blotting for LC3B and LAMP-2. The localization of regulators of autophagy was examined by immunohistochemistry. Culture of BeWo cells was used to investigate whether nutrient and/or oxygen deprivation can induce autophagy in trophoblast. Autophagy predominantly localized to the syncytiotrophoblast layer and autophagosomes were more frequent in FGR. The regulators LAMP-2, LC3B, Beclin-1, ATG 5, ATG9 and ATG16L1 were all present in villous trophoblast. LAMP-2 immunostaining was more punctate in FGR. In BeWo cells, culture in reduced oxygen tension and/or serum depleted conditions led to the appearance of autophagosomes which was associated with changes in LAMP-2 configuration. We conclude that autophagy in human term placenta may be involved in the placental dysfunction present in FGR.