Distribution and potential roles of syncytin protein in normal and diabetic human placentas

The human placenta is a unique organ which regulates all metabolic activities between mother and fetus throughout pregnancy. To this respect, healthy pregnancy is closely related with normal placenta development. Previous studies have showed that the fusion of trophoblast cells constitutes a key process of placental morphogenesis. It has been showed by recent studies Syncytin proteins, which are belonged to Human Endogenous Retroviruses (HERV) family, play a crucial role during the fusion of trophoblast cells and placental development. However, there is scarce information about whether Syncytin proteins have any role in gestational diabetic placenta pathology. Therefore we hypothesized that the expression of Syncytin proteins and their receptors show abnormal expression in gestational diabetic placentas compared to control placenta. We aimed to determine altered Syncytin proteins and their receptors expression by descriptive experiments. In this study, human placentas from uncomplicated pregnancies, gestational diabetic placentas and human first trimester placenta tissues were prepared for light microscopy, western blot and electron microscopy investigations. The cellular localizations of Syncytin 1, Syncytin 2, SLC1A5 (receptor of Syncytin 1) and MFSD2 (receptor of Syncytin 2) were determined by immunohistochemistry in placental sections. The protein expression level of Syncytin 1, Syncytin 2, SLC1A5 and MFSD2 were investigated by western blot. Moreover, the difference of ultrastructural and three-dimensional features in human normal term placenta, gestational diabetic term placenta and first trimester placenta tissues were identified by transmission (TEM) and scanning (SEM) electron microscopy. According to our results, the immunolocalization of Syncytin 1, Syncytin 2, SLC1A5 and MFSD2 proteins were observed significantly in trophoblast layer and also some stromal cells were positive in placental villi. When expression levels of Syncytin proteins and their receptors were compared between experimental groups, Syncytin 1 expression Syncytin2 and MFSD2 expressions were notably decreased in diabetic placentas compared to control term placenta. In addition that, expression of SLC1A5 increased dramatically in early pregnancy compared to control term placenta. According to our electron microscopy results, in gestational diabetic placenta, tissue integrity of syncytiotrophoblast layer was lost and vacuolisation was increased relatively compared to control term placenta. In our study, we showed for the first time in literature that expressions of Syncytin proteins and their receptors were determined in gestational diabetic placenta. Decreased Syncytin2 and MFSD2 expressions might cause abnormal syncytiotrophoblasts formation and potentially involve in diabetic placental pathology. Abnormal Syncytin 2 and receptor expression in gestational diabetic placentas may contribute to understand the aetiology of diabetic placenta. Keywords: Human placenta, Gestational Diabetes, Syncytin 1, Syncytin 2, SLC1A5, MFSD2.