Variations in blood levels of the anti-fusogenic endogenous retroviral protein suppressyn are associated with fetal growth outcome in preeclampsia.

Abstract

Suppressyn, a placenta-specific protein characterized by its inhibitory effect on trophoblast cell fusion, is considered to play a direct role in the formation and maintenance of placental villi in humans. Given the potential involvement of aberrant suppressyn expression in the development of placenta-dependent disorders, we focused our analysis on hypertensive disorders of pregnancy, with particular emphasis on preeclampsia (PE). PE is a leading cause of maternal morbidity and mortality worldwide and poses a serious risk to fetal growth and survival. As delivery remains the only definitive treatment and no effective methods for prevention or early diagnosis have been established, there is an urgent need for investigation from novel perspectives. In the present study, we investigated the expression profiles of suppressyn and fusion-associated molecules in human placental villous tissues and maternal blood samples. Our analysis revealed two key findings: (1) suppressyn protein levels are significantly reduced in placentas from pregnancies complicated by PE with fetal growth restriction (FGR), and (2) suppressyn secretion is modulated in an ASCT2 expression-dependent manner, suggesting that the intracellular balance between suppressyn and this transporter may play a critical role in the pathophysiology of PE and in maintaining placental function. Detectable alterations in maternal serum concentrations of secreted suppressyn in pregnancies affected by hypertensive disorders of pregnancy may offer a novel biomarker that monitors placental developmental status in these disease states. These findings may also provide new insights into the molecular underpinnings of PE and a mechanistic link between suppressyn dysregulation and the development of FGR.