Syncytin-1 and Glial Cells Missing a: Hypoxia-Induced Deregulated Gene Expression along with Disordered Cell Fusion in Primary Term Human Trophoblasts

Abstract

Background/Aims: Pre-eclampsia, a major cause of perinatal morbidity, is characterized by alterations in placental oxygen availability and trophoblast differentiation. We investigated how different levels of hypoxia alter the expression of syncytin-1, glial cells missing a (GCMa) and syncytin-1 receptor ASCT2 and affect syncytialization in primary term human trophoblasts. Methods: Cells were incubated at 1, 3, 6 and 21% O₂ for 24, 48 and 72 h with or without cyclic adenosine monophosphate (cAMP). Gene expression was analyzed by real-time PCR. Syncytialization was assessed using β-human chorionic gonadotropin measurement and desmoplakin immunostaining. Results: Following incubation with cAMP at 21% O₂, peak gene expression of syncytin-1 and GCMa was found after 24 h along with syncytium formation at 72 h. Conversely, incubation at 1% O₂ led to a time-dependent reduction of GCMa and syncytin-1 at the transcriptional level. Cell fusion occurred at 21 and 6% O₂ and was suppressed at 1% O₂. ASCT2 mRNA levels were preserved at normoxia and downregulated at 1% O₂ after 48 h. Conclusion: Our data support the premise that the expression of GCMa and syncytin-1 precedes syncytialization of trophoblasts, e.g. at 6% O₂, which is assumed to resemble physiological conditions. Severe hypoxia is associated with reduced GCMa and syncytin-1 transcripts and altered fusion of primary trophoblasts.