Gynecologic and Obstetric Investigation 2009; 68: 9-18. <http://content.karger.com/ProdukteDB/produkte.asp?typ=pdf&doi=209396> © 2009 S. Karger AG, Basel

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% 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 _ -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. Show more