Inducible knockout of syncytin-a leads to poor placental glucose transport in mice

• Published in: Placenta (Eastbourne) 2022-04, Vol.121, p.155-163
• Main Authors: Wang, Ya-Nan, Ye, Yi-Xin, Guo, Ze-Wen, Xiong, Zhe-Lei, Sun, Qi-Si, Zhou, Da, Jiang, Shi-Wen, Chen, Haibin
• Format: Article
• Language: English
• Subjects: Animals; Connexin 26 - metabolism; Female; Fetal growth restriction; Fetal Growth Retardation - genetics; Fetal Growth Retardation - metabolism; Gene Products, env - genetics; Gene Products, env - metabolism; Glucose - metabolism; Glucose transporter; Glucose Transporter Type 1 - genetics; Glucose Transporter Type 1 - metabolism; Mice; Mice, Knockout; Placenta - metabolism; Pregnancy; Pregnancy Proteins; Syncytin-A; Trophoblast; Trophoblasts - metabolism
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2022.03.016

Cell-cell fusion of cytotrophoblasts into the syncytiotrophoblast layer is a key process in placental development. Syncytin, an endogenous retroviral envelope protein, is expressed in placental trophoblasts and specifically mediates syncytiotrophoblast layer formation. Syncytin deficiency has been observed in fetal growth-restricted placentas. Abnormal fetal growth, especially fetal growth restriction, is associated with the decreased expression of glucose transporters. Here, we aimed to determine the role of syncytin in fetal growth restriction in placental glucose transport capacity. To better explore the function of syncytin in fetal growth-restricted placenta, we generated an inducible knockout mouse model of syncytin-a gene. The expression levels of glucose transporters in BeWo cells were measured before and after HERV-W knockdown. Syncytin-A disruption was associated with significant abnormalities in placental and fetal development in mice. Syncytin-A destruction causes extensive abnormalities in the maternal-fetal exchange structures in the labyrinth, including an extremely reduced number and dramatically irregular distribution of fetal vessels. Moreover, glucose transporter 1, glucose transporters 3, and connexin 26 expression levels decreased after E14.5. Consistently, low glucose transporter 1, glucose transporter 3, and connexin 26 levels were observed in HERV-W-silenced BeWo cells. Syncytin-A is crucial for both syncytiotrophoblast layer development and morphogenesis, suggesting that syncytin-A disruption leads to fetal growth restriction associated with abnormalities in the maternal-fetal exchange barrier and decreased glucose transport. •Placental transporter capacity is crucial for fetal development.•The disruption of syncytin led to poor placental glucose transport capacity.•Low expression of Syncytin was related to FGR.