Syncytin-1 and glial cells missing a: hypoxia-induced deregulated gene expression along with disordered cell fusion in primary term human trophoblasts.
OBJECTIVE
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.


CONCLUSIONS
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.
Wich
C
C
Children's and Adolescents' Hospital, University of Erlangen-Nuremberg, Erlangen, Germany.
Kausler
S
S
Dotsch
J
J
Rascher
W
W
Knerr
I
I