Department of Gynecology and Obstetrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
Laboratory for Reproductive Immunology, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.
Curr Mol Med. 2019;19(7):494-505. doi: 10.2174/1566524019666190520100422.
An increasing number of studies have described the pathological changes of placenta tissues in gestational diabetes mellitus (GDM), although the underlying mechanisms involved in this process remain uncertain. The aim of the present study was to verify the possible role of microRNA-137 (miR)-137 and FNDC5 in regulating the biological function of trophoblasts in high glucose (HG) conditions during the GDM period.
Expression levels of miR-137 and FNDC5 were measured in placenta specimens, the HG-treated trophoblast cell line HTR-8/SVneo and miR-137- overexpressing HTR-8/SVneo cells using reverse transcription quantitative-PCR or western blotting. The viability of HTR-8/SVneo cells was tested using a Cell Counting kit- 8 (CCK8) assay, with cell migration assessed using scratch and transwell assays.
It was observed that the expression levels of miR-137 were increased and the expression levels of FNDC5 were decreased in the placenta tissues of women with severe GDM and in HG-exposed HTR-8/SVneo cells. In addition, upregulating miR-137 in HTR-8/SVneo cells downregulated the expression levels of FNDC5. The viability and migration of HTR-8/SVneo cells were suppressed by increased miR-137 expression levels, and upregulating FNDC5 in miR-137-overexpressing HTR-8/SVneo cells resulted in the reversal of all these effects.
The data from the present study suggest that miR-137 suppresses the viability and migration of trophoblasts via downregulating FNDC5 in GDM, which may contribute to the pathology of placenta tissues and occurrence of adverse pregnancy outcomes.
越来越多的研究描述了妊娠期糖尿病(GDM)胎盘组织的病理变化,尽管涉及这一过程的潜在机制仍不确定。本研究旨在验证 microRNA-137(miR-137)和 FNDC5 在调节 GDM 期间高葡萄糖(HG)条件下滋养细胞生物学功能中的可能作用。
使用逆转录定量 PCR 或 Western blot 检测胎盘标本、HG 处理的滋养细胞系 HTR-8/SVneo 和 miR-137 过表达的 HTR-8/SVneo 细胞中 miR-137 和 FNDC5 的表达水平。使用 Cell Counting kit-8(CCK8)测定 HTR-8/SVneo 细胞的活力,用划痕和 Transwell 测定法评估细胞迁移。
观察到严重 GDM 妇女的胎盘组织和 HG 暴露的 HTR-8/SVneo 细胞中 miR-137 的表达水平增加,FNDC5 的表达水平降低。此外,在 HTR-8/SVneo 细胞中上调 miR-137 下调了 FNDC5 的表达水平。HTR-8/SVneo 细胞的活力和迁移被上调的 miR-137 表达水平抑制,在 miR-137 过表达的 HTR-8/SVneo 细胞中上调 FNDC5 导致所有这些效应的逆转。
本研究的数据表明,miR-137 通过下调 GDM 中的 FNDC5 抑制滋养细胞的活力和迁移,这可能有助于胎盘组织的病理学和不良妊娠结局的发生。