Association of dysfunctional synapse defective 1 (SYDE1) with restricted fetal growth - SYDE1 regulates placental cell migration and invasion
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- 作者：Hsiao-Fan Lo ; Ching-Yen Tsai ; Chie-Pein Chen ; Liang-Jie Wang ; Yun-Shien Lee ; Chia-Yu Chen ; Chung-Tiang Liang ; Mei-Leng Cheong and Hungwen Chen
- 刊名：The Journal of Pathology
- 出版年：2017
- 出版时间：February 2017
- 年：2017
- 卷：241
- 期：3
- 页码：324-336
- 全文大小：6004K
- ISSN：1096-9896
文摘
The transcription factor glial cells missing 1 (GCM1) regulates trophoblast differentiation and function during placentation. Decreased GCM1 expression is associated with pre-eclampsia, suggesting that abnormal expression of GCM1 target genes may contribute to the pathogenesis of pregnancy complications. Here we identified a novel GCM1 target gene, synapse defective 1 (<i>SYDE1i>), which encodes a RhoGAP that is highly expressed in human placenta, and demonstrated that SYDE1 promotes cytoskeletal remodelling and cell migration and invasion. Importantly, genetic ablation of murine <i>Syde1i> results in small fetuses and placentas with aberrant phenotypes in the placental–yolk sac barrier, maternal–trophoblast interface, and placental vascularization. Microarray analysis revealed altered expression of renin-1, angiotensin I converting enzyme 2, angiotensin II type 1a receptor, and membrane metalloendopeptidase of the renin–angiotensin system in <i>Syde1i>-knockout placenta, which may compensate for the vascular defects to maintain normal blood pressure. As pregnancy proceeds, growth restriction of the <i>Syde1−/−i> fetuses and placentas continues, with elevated expression of the Syde1 homologue Syde2 in placenta. Syde2 may compensate for the loss of Syde1 function because SYDE2, but not the GAP-dead SYDE2 mutant, reverses migration and invasion activities of <i>SYDE1i>-knockdown JAR trophoblast cells. Clinically, we further detected decreased SYDE1 expression in preterm and term IUGR placentas compared with gestational age-matched controls. Our study suggests a novel mechanism for GCM1 and SYDE1 in regulation of trophoblast cell migration and invasion during placental development and that decreased SYDE1 expression is associated with IUGR. Copyright