The inhibition of placental mTOR signaling leads to fetal growth restriction with abnormal glucose metabolism in different anatomical regions of placentas
Qian Xu , Jingjing Wang , Yajing Li , Hui Lei , Ni Jin , Jie Lu , Chenxi Qian , Jianhua Zhang , Jie Dong , Xiaohong Wang
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引用次数: 0
Abstract
Introduction
Fetal growth restriction (FGR) is a common pregnancy complication with significant impact on obstetric and birth outcomes. Increasing evidence shows that the inhibition of placental mechanistic target of rapamycin (mTOR) signaling is closely related to FGR. However, the pathogenesis of FGR is not fully consistent presently, which is subject to the methodological divergence.
Methods
Rapamycin was used to construct the FGR mouse model. Hematoxylin & eosin (HE) and periodic acid-schiff (PAS) staining were used to analyze the morphology of mouse placenta. Western blot was used to analyze the expression levels of glucose transporters and key enzymes associated with glycogen metabolism in human/mouse placental tissues in different anatomic layers. HTR-8 cells were treated with dimethyl sulfoxide (DMSO) or rapamycin (2 mM) for 24 h. Cell viability was detected by CCK8 kit. In addition, glycogen concentration in placental tissue or cell samples was detected by Glycogen Assay Kit.
Results
Firstly, we observed a significant reduction of glucose content in different anatomical regions of human small-for-gestational-age (SGA) placenta, also glucose metabolism was undermined to some extent. Then, we found that FGR placentas showed abnormal morphological changes, the glycogen levels in FGR placentas were significantly reduced by quantitative detection. Meanwhile, the expression levels of glucose transporters, Gys1 and p-Gsk3β in FGR placentas were reduced compared to controls. The HTR-8 cells treated with rapamycin revealed decreasing mTOR activity and glycogen levels. In addition, glucose transporter, GYS1, p-GSK3β expressions were all significantly reduced and t-GSK3β level was significantly elevated.
Discussion
Overall, our data indicate that inhibition of placental mTOR signaling may contribute to the occurrence of FGR by altering glucose metabolism.
期刊介绍：
Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.
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