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

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% O(2) 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 beta-human chorionic gonadotropin measurement and desmoplakin immunostaining. RESULTS: Following incubation with cAMP at 21% O(2), peak gene expression of syncytin-1 and GCMa was found after 24 h along with syncytium formation at 72 h. Conversely, incubation at 1% O(2) led to a time-dependent reduction of GCMa and syncytin-1 at the transcriptional level. Cell fusion occurred at 21 and 6% O(2) and was suppressed at 1% O(2). ASCT2 mRNA levels were preserved at normoxia and downregulated at 1% O(2) 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% O(2), which is assumed to resemble physiological conditions. Severe hypoxia is associated with reduced GCMa and syncytin-1 transcripts and altered fusion of primary trophoblasts.