These results suggest that the NR4A sub-family of nuclear orphan receptors has a role in trophoblastic cell differentiation.
However, a considerable amount of cell death occurred after forskolin or hCG treatment as compared to the control siRNA-transfected cells. Simultaneously silencing all three NR4A sub-family members significantly downregulated forskolin- and hCG-mediated BeWo cell fusion and/or hCG secretion. After silencing any one member of the NR4A sub-family, an increase in the transcript levels of the other sub-family members was observed, indicating a compensatory effect due to their functional redundancy. Silencing Nor-1, Nurr-1 or Nur-77 individually did not show any effect on forskolin-, hCG- and/or GnRH-mediated BeWo cell fusion and/or hCG secretion. A similar significant increase was observed at the respective protein levels after 2 and 48 h of treatment with forskolin, hCG or GnRH. The expression of NR4A sub-family members was also found to be upregulated in BeWo cells after treatment with hCG and GnRH.
The maximum increase was observed after 2 h, with a second peak in the expression levels after 48 h. Their transcript levels were found to be significantly upregulated in BeWo cells treated with forskolin. Here, we investigate the relevance of Nor-1, Nurr-1 and Nur-77 in trophoblastic cell differentiation.
Nur-77, a member of the NR4A sub-family of nuclear orphan receptors, is downregulated in the placentae of pre-eclamptic women.
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