title: Involvement of nephrin in human placental trophoblast syncytialization.
abstract: The placenta has numerous functions, such as transporting oxygen and nutrients and building the immune tolerance of the fetus. Cell fusion is an essential process for placental development and maturation. In human placental development, mononucleated cytotrophoblast (CTB) cells can fuse to form a multinucleated syncytiotrophoblast (STB), which is the outermost layer of the placenta. Nephrin is a transmembrane protein that belongs to the Ig superfamily. Previous studies have shown that nephrin contributes to the fusion of myoblasts into myotubes in zebrafish and mice, presenting a functional conservation with its Drosophila ortholog sticks and stones. However, whether nephrin is involved in trophoblast syncytialization remains unclear. In this study, we report that nephrin was localized predominantly in the CTB cells and STB of human placenta villi from first trimester to term pregnancy. Using a spontaneous fusion model of primary CTB cells, the expression of nephrin was found to be increased during trophoblast cell fusion. Moreover, the spontaneous syncytialization and the expression of syncytin 2, connexin 43, and human chorionic gonadotropin beta were significantly inhibited by nephrin-specific siRNAs. The above results demonstrate that nephrin plays an important role in trophoblast syncytialization.
authors.affiliation: Department of Biochemistry and Molecular Biology College of Basic Medical Science, Harbin Medical University, Harbin 150081, People's Republic of China State Key Laboratory of Reproductive Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences Beijing 100039, People's Republic of China Key Laboratory of Longevity and Ageing-related Diseases Ministry of Education, Guangxi Medical University, Nanning 530021, People's Republic of China Department of Biochemistry and Molecular Biology College of Basic Medical Science, Harbin Medical University, Harbin 150081, People's Republic of China State Key Laboratory of Reproductive Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences Beijing 100039, People's Republic of China Key Laboratory of Longevity and Ageing-related Diseases Ministry of Education, Guangxi Medical University, Nanning 530021, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology College of Basic Medical Science, Harbin Medical University, Harbin 150081, People's Republic of China State Key Laboratory of Reproductive Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences Beijing 100039, People's Republic of China Key Laboratory of Longevity and Ageing-related Diseases Ministry of Education, Guangxi Medical University, Nanning 530021, People's Republic of China Department of Biochemistry and Molecular Biology College of Basic Medical Science, Harbin Medical University, Harbin 150081, People's Republic of China State Key Laboratory of Reproductive Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences Beijing 100039, People's Republic of China Key Laboratory of Longevity and Ageing-related Diseases Ministry of Education, Guangxi Medical University, Nanning 530021, People's Republic of China.
authors.forename: Ru
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry and Molecular Biology College of Basic Medical Science, Harbin Medical University, Harbin 150081, People's Republic of China State Key Laboratory of Reproductive Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences Beijing 100039, People's Republic of China Key Laboratory of Longevity and Ageing-related Diseases Ministry of Education, Guangxi Medical University, Nanning 530021, People's Republic of China Department of Biochemistry and Molecular Biology College of Basic Medical Science, Harbin Medical University, Harbin 150081, People's Republic of China State Key Laboratory of Reproductive Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences Beijing 100039, People's Republic of China Key Laboratory of Longevity and Ageing-related Diseases Ministry of Education, Guangxi Medical University, Nanning 530021, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology College of Basic Medical Science, Harbin Medical University, Harbin 150081, People's Republic of China State Key Laboratory of Reproductive Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences Beijing 100039, People's Republic of China Key Laboratory of Longevity and Ageing-related Diseases Ministry of Education, Guangxi Medical University, Nanning 530021, People's Republic of China Department of Biochemistry and Molecular Biology College of Basic Medical Science, Harbin Medical University, Harbin 150081, People's Republic of China State Key Laboratory of Reproductive Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences Beijing 100039, People's Republic of China Key Laboratory of Longevity and Ageing-related Diseases Ministry of Education, Guangxi Medical University, Nanning 530021, People's Republic of China.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology College of Basic Medical Science, Harbin Medical University, Harbin 150081, People's Republic of China State Key Laboratory of Reproductive Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences Beijing 100039, People's Republic of China Key Laboratory of Longevity and Ageing-related Diseases Ministry of Education, Guangxi Medical University, Nanning 530021, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology College of Basic Medical Science, Harbin Medical University, Harbin 150081, People's Republic of China State Key Laboratory of Reproductive Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences Beijing 100039, People's Republic of China Key Laboratory of Longevity and Ageing-related Diseases Ministry of Education, Guangxi Medical University, Nanning 530021, People's Republic of China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology College of Basic Medical Science, Harbin Medical University, Harbin 150081, People's Republic of China State Key Laboratory of Reproductive Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences Beijing 100039, People's Republic of China Key Laboratory of Longevity and Ageing-related Diseases Ministry of Education, Guangxi Medical University, Nanning 530021, People's Republic of China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology College of Basic Medical Science, Harbin Medical University, Harbin 150081, People's Republic of China State Key Laboratory of Reproductive Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences Beijing 100039, People's Republic of China Key Laboratory of Longevity and Ageing-related Diseases Ministry of Education, Guangxi Medical University, Nanning 530021, People's Republic of China yxg301@163.com fujiejun@126.com.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology College of Basic Medical Science, Harbin Medical University, Harbin 150081, People's Republic of China State Key Laboratory of Reproductive Biology Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China University of Chinese Academy of Sciences Beijing 100039, People's Republic of China Key Laboratory of Longevity and Ageing-related Diseases Ministry of Education, Guangxi Medical University, Nanning 530021, People's Republic of China yxg301@163.com fujiejun@126.com.
authors.forename: Jiejun
authors.initials: J
authors.lastname: Fu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002459:Cell Fusion; D002478:Cells, Cultured; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000235:genetics / Q000378:metabolism; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015726:Giant Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010920:Placenta / Q000166:cytology* / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D018031:Connexin 43; C518353:ERVFRD-1 protein, human; C500216:GJA1 protein, human; D008565:Membrane Proteins; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C113267:nephrin