title: Syncytin-1 modulates placental trophoblast cell proliferation by promoting G1/S transition.
abstract: Placental syncytiotrophoblasts formed by the fusion of cytotrophoblasts constitute the interface between maternal and fetal circulations. The syncytium, composed of a continuous layer of syncytiotrophoblasts, assumes the fetal-maternal nutrient exchange, placental barrier, and endocrine functions important for the maintenance of normal pregnancy. Syncytin-1, an endogenous retroviral gene product, mediates the fusion of cytotrophoblasts. While the fusogenic function of syncytin-1 has been well established, little is known regarding its nonfusogenic activities. This study investigates the role of syncytin-1 in trophoblast proliferation. We found that syncytin-1 knockdown significantly inhibited BeWo cell growth and DNA synthesis. Moreover, time course studies on key cell cycle regulators demonstrated an upregulation of p15 and downregulation of CDK4, E2F1, PCNA, and c-Myc, which consequently led to a reduced level of CDK1. These results, together with those from flow cytometry analysis, indicated that syncytin-1 knockdown blocked the G1/S transition phase of the cell cycle. Moreover, syncytin-1 overexpression promoted CHO cell proliferation and led to changes opposite to those observed in syncytin-1 knockdown experiments, confirming the critical role of syncytin-1 for G1/S transition. Thus, syncytin-1, through both nonfusogenic and fusogenic, functions, may co-regulate the input (proliferation) and output (fusion) of the cytotrophoblast "pool". Such co-regulation could be an efficient way to achieve the balance between these two opposing processes, which is required for syncytium homeostasis. Since decreased syncytin-1 expression has been shown to be associated with preeclamptic and hypoxic condition, insufficient replenishing of the cytotrophoblast "pool" may contribute to syncytium deficiency, a critical pathological change frequently found in preeclamptic placentas.
authors: The Second Affiliated Hospital of Xi'an Jiaotong University, School of Medicine, Xi'an, Shaanxi 710004, China.
authors: Qiang
authors: Q
authors: Huang
authors: Jinping
authors: J
authors: Li
authors: Fengchao
authors: F
authors: Wang
authors: Matthew T
authors: MT
authors: Oliver
authors: Tracy
authors: T
authors: Tipton
authors: Ya
authors: Y
authors: Gao
authors: Shi-Wen
authors: SW
authors: Jiang
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D016466:CHO Cells; D002460:Cell Line; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000378:metabolism; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015686:Gene Products, env / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
chemical_list: D050762:Cyclin-Dependent Kinase Inhibitor p15; D050687:E2F1 Transcription Factor; D015686:Gene Products, env; D011257:Pregnancy Proteins; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; C405335:syncytin; D016203:CDC2 Protein Kinase; D051358:Cyclin-Dependent Kinase 4