The role of syncytins in human reproduction and reproductive organ cancers

Abstract

Human life begins with sperm and oocyte fusion. After fertilization, various fusion events occur during human embryogenesis and morphogenesis. For example, the fusion of trophoblastic cells constitutes a key process for normal placental development. Fusion in the placenta is facilitated by syncytin 1 and syncytin 2. These syncytins arose from retroviral sequences that entered the primate genome 25 million and more than 40 million years ago respectively. About 8% of the human genome consists of similar human endogenous retroviral (HERVs) sequences. Many are inactive because of mutations or deletions. However, the role of the few that remain transcriptionally active has not been fully elucidated. Syncytin proteins maintain cell-cell fusogenic activity based on env gene-mediated viral cell entry. In this review, we summarize how syncytins and their receptors are involved in fusion events during human reproduction. The significance of syncytins in tumorigenesis is also discussed.Reproduction (2016) 152 R167-R178

Epigenetic Control of Human Endogenous Retrovirus Expression: Focus on Regulation of Long-Terminal Repeats (LTRs)

“…Moreover, problems during gestational diabetes are linked to aberrant expression of syncytin-2 and its receptor, MFSD2 [64]. The role of syncytins in the placenta is discussed in detail in a recent review [65]; here, we are concerned with the epigenetic regulation of syncytin expression.…”

“…High levels of syncytin-2 are detected in the testes, which is another tissue that displays global hypomethylation and this is thought to favour HERV expression [65]. Syncytin-1 is also thought to be involved in fertilisation, possibly contributing to the fusion of gametes.…”

“…Syncytin-1 is also thought to be involved in fertilisation, possibly contributing to the fusion of gametes. Sperm express syncytin-1 on the cell surface whereas oocytes do not; instead, oocytes express the syncytin-1 receptor SLC1A5 [65]. Finally, HERV-K particles have also been detected in human placenta [72] but the functional significance of this, if any, remains unclear.…”

Decreased miR- 31 Suppress Cell Migration and Proliferation By Targeting Syncytin-1 in Pancreatic Carcinoma

“…Studies have indicated that syncytin-1 and estrogen stimulation induction is closely related, and which is in the cytotrophoblast fusion into the process of syncytium trophoblast key action [15]. It has been con rmed that the expression level of syncytin-1 is related to clinical manifestations in organ cancer patients [16], acute myeloid leukemia [17], breast cancer [18], endometrial carcinomas [19], ovarian cancer and colorectal cancer [20,21].…”

Human Placenta Expresses α2-Adrenergic Receptors and May Be Implicated in Pathogenesis of Preeclampsia and Fetal Growth Restriction

“…16,17 Chief among them are syncytin-1 and syncytin-2, which are considered hallmarks of terminal differentiation of placental trophoblast linage. 18 The synthesis and expression of syncytins depends on the cAMP/protein kinase A pathway as demonstrated through experiments that involve pharmacologic stimulation of cytotrophoblast-like (BeWo) cells with the adenylate cyclase activator and intracellular cAMP-elevating agent forskolin. 16,19 From the above experimental data it is tempting to speculate that aberrant expression and activation of a 2 ARs could disrupt placental development, leading to pathologic processes.…”