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- W2582204867 abstract "Are hypoxia-inducible factors (HIF) responsible for the potentiation of inhibin alpha subunit (INHA) gene expression in primary cultures of human term cytotrophoblasts under low-oxygen tension?Both HIF1A and endothelial PAS domain protein 1 (EPAS1) are involved in the potentiation of INHA gene upregulation in cytotrophoblasts cultured under hypoxia.During the in vitro differentiation of cytotrophoblasts into syncytiotrophoblasts under 21% O2, INHA expression increases. This expression is further increased when cells are cultured under low-oxygen tension (e.g. 2.5% O2). Moreover, in pregnancy-related diseases, such as pre-eclampsia or intrauterine growth restriction (IUGR), in which hypoxia is suspected to be responsible for the abnormal placental development, maternal serum concentration of inhibin A is elevated.Cytotrophoblasts were isolated and purified from human term placentas (n = 6). Cells were cultured under 21% O2, and allowed to differentiate for 48 h. A first group of cells was treated for 16 h under 21% O2 with dimethyloxalylglycine (DMOG) or deferoxamine (DFX), molecules that mimic hypoxia by inhibiting HIF1 proteasomal degradation. Involvement of HIF1A and EPAS1 (also known as HIF2A), two HIF isoforms expressed in trophoblasts, was shown by treating another group of cells cultured under 2.5% O2 with specific inhibitors of HIF1A and EPAS1 for 16 h. INHA mRNA expression was assessed by real-time PCR and secreted inhibin A was quantified by ELISA. The role of HIF1A and EPAS1 in INHA transcriptional regulation was further confirmed by cotransfecting primary cytotrophoblasts with a luciferase reporter plasmid containing a 3.9 kb INHA promoter and plasmids allowing overexpression of HIF1A and EPAS1.Placentas were obtained after vaginal or elective cesarean delivery from uncomplicated pregnancies at term (n≥ 4). The methods used were hormone measurements in the cell supernatants by enzyme-linked immunosorbent assay, real-time quantitative PCR, western blotting, immunofluorescence microscopy and transient transfection.HIF1 protein stabilization with DMOG and DFX increased 21% O2-induced INHA mRNA and protein upregulation (P < 0.05 versus control), while hypoxia-induced INHA upregulation was repressed by HIF1A and EPAS1 inhibitors (P < 0.05 versus control). In transfection experiments of primary term cytotrophoblasts, cloned INHA promoter transcriptional activity was increased by 2.5% O2 compared to 21% O2 (P < 0.05). Overexpression of both HIF1A and EPAS1 under 21% O2 increased cloned INHA transcriptional activity (P < 0.001 versus control).Not applicable.HIF1A and EPAS1 may regulate INHA expression by binding to an hypoxia-responsive element within the promoter, but we were unable to identify such an element. Inhibition of HIF1A and EPAS1 did not completely suppress upregulation of INHA expression suggesting that other transcription factors, not identified or studied here, are involved.Our data suggest that the effect of HIF1 proteins on INHA gene promoter activity may be indirect. By demonstrating the role of HIF1A and especially EPAS1 in INHA gene upregulation under hypoxia, the results suggest that HIF1 proteins may become new therapeutic targets in the treatment of pregnancy-related diseases such as pre-eclampsia or IUGR.This work was fully supported by 'Fetus for Life' charity. C. Depoix was supported by a fellowship 'Fonds de Recherche Clinique' from 'Fondation Saint-Luc', Belgium. The authors declare that there is no conflict of interest regarding the publication of this paper." @default.
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- W2582204867 date "2017-01-23" @default.
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- W2582204867 title "HIF1A and EPAS1 potentiate hypoxia-induced upregulation of inhibin alpha chain expression in human term cytotrophoblasts in vitro" @default.
- W2582204867 cites W1483762900 @default.
- W2582204867 cites W1520294062 @default.
- W2582204867 cites W171819190 @default.
- W2582204867 cites W1778217829 @default.
- W2582204867 cites W1826787066 @default.
- W2582204867 cites W1849560193 @default.
- W2582204867 cites W1919217119 @default.
- W2582204867 cites W1923069688 @default.
- W2582204867 cites W1946637896 @default.
- W2582204867 cites W1965430573 @default.
- W2582204867 cites W1967832920 @default.
- W2582204867 cites W1968972540 @default.
- W2582204867 cites W1969037707 @default.
- W2582204867 cites W1971584511 @default.
- W2582204867 cites W1975545468 @default.
- W2582204867 cites W1986744382 @default.
- W2582204867 cites W1999913538 @default.
- W2582204867 cites W2000976163 @default.
- W2582204867 cites W2003632029 @default.
- W2582204867 cites W2009163575 @default.
- W2582204867 cites W2010356452 @default.
- W2582204867 cites W2010386340 @default.
- W2582204867 cites W2013764309 @default.
- W2582204867 cites W2017771409 @default.
- W2582204867 cites W2019759067 @default.
- W2582204867 cites W2020968632 @default.
- W2582204867 cites W2023447334 @default.
- W2582204867 cites W2030918859 @default.
- W2582204867 cites W2032148842 @default.
- W2582204867 cites W2032517238 @default.
- W2582204867 cites W2034626250 @default.
- W2582204867 cites W2034966324 @default.
- W2582204867 cites W2036469757 @default.
- W2582204867 cites W2037880480 @default.
- W2582204867 cites W2042216712 @default.
- W2582204867 cites W2045890236 @default.
- W2582204867 cites W2062787442 @default.
- W2582204867 cites W2064224644 @default.
- W2582204867 cites W2069993321 @default.
- W2582204867 cites W2074824347 @default.
- W2582204867 cites W2079121632 @default.
- W2582204867 cites W2085538044 @default.
- W2582204867 cites W2085609942 @default.
- W2582204867 cites W2088401580 @default.
- W2582204867 cites W2089026277 @default.
- W2582204867 cites W2093014461 @default.
- W2582204867 cites W2097321304 @default.
- W2582204867 cites W2102493308 @default.
- W2582204867 cites W2107277218 @default.
- W2582204867 cites W2107410714 @default.
- W2582204867 cites W2107577013 @default.
- W2582204867 cites W2107754056 @default.
- W2582204867 cites W2111843622 @default.
- W2582204867 cites W2116384502 @default.
- W2582204867 cites W2125887885 @default.
- W2582204867 cites W2127928842 @default.
- W2582204867 cites W2138670825 @default.
- W2582204867 cites W2142786915 @default.
- W2582204867 cites W2144625075 @default.
- W2582204867 cites W2146169796 @default.
- W2582204867 cites W2150949422 @default.
- W2582204867 cites W2154652221 @default.
- W2582204867 cites W2167104992 @default.
- W2582204867 cites W2167786713 @default.
- W2582204867 cites W2167845320 @default.
- W2582204867 cites W2169558257 @default.
- W2582204867 cites W2332017164 @default.
- W2582204867 cites W2418749033 @default.
- W2582204867 doi "https://doi.org/10.1093/molehr/gax002" @default.
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