{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:32:04Z","timestamp":1785461524610,"version":"3.56.0"},"reference-count":83,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T00:00:00Z","timestamp":1706140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Quebec-Wales joint call for projects program (Welsh Government and the Government of Qu\u00e9bec","award":["MRIF-FSR-PCO 02.805-6690854"],"award-info":[{"award-number":["MRIF-FSR-PCO 02.805-6690854"]}]},{"name":"Quebec-Wales joint call for projects program (Welsh Government and the Government of Qu\u00e9bec","award":["RGPIN\/6516-2014"],"award-info":[{"award-number":["RGPIN\/6516-2014"]}]},{"name":"Quebec-Wales joint call for projects program (Welsh Government and the Government of Qu\u00e9bec","award":["2018-RS4-203214"],"award-info":[{"award-number":["2018-RS4-203214"]}]},{"name":"Natural Sciences and Engineering Research Council","award":["MRIF-FSR-PCO 02.805-6690854"],"award-info":[{"award-number":["MRIF-FSR-PCO 02.805-6690854"]}]},{"name":"Natural Sciences and Engineering Research Council","award":["RGPIN\/6516-2014"],"award-info":[{"award-number":["RGPIN\/6516-2014"]}]},{"name":"Natural Sciences and Engineering Research Council","award":["2018-RS4-203214"],"award-info":[{"award-number":["2018-RS4-203214"]}]},{"name":"Fonds Qu\u00e9b\u00e9cois de la Recherche sur la Nature et les Technologies-R\u00e9seau Qu\u00e9b\u00e9cois en Reproduction FQRNT RQR","award":["MRIF-FSR-PCO 02.805-6690854"],"award-info":[{"award-number":["MRIF-FSR-PCO 02.805-6690854"]}]},{"name":"Fonds Qu\u00e9b\u00e9cois de la Recherche sur la Nature et les Technologies-R\u00e9seau Qu\u00e9b\u00e9cois en Reproduction FQRNT RQR","award":["RGPIN\/6516-2014"],"award-info":[{"award-number":["RGPIN\/6516-2014"]}]},{"name":"Fonds Qu\u00e9b\u00e9cois de la Recherche sur la Nature et les Technologies-R\u00e9seau Qu\u00e9b\u00e9cois en Reproduction FQRNT RQR","award":["2018-RS4-203214"],"award-info":[{"award-number":["2018-RS4-203214"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Interleukin-6 (IL-6) superfamily cytokines play critical roles during human pregnancy by promoting trophoblast differentiation, invasion, and endocrine function, and maintaining embryo immunotolerance and protection. In contrast, the unbalanced activity of pro-inflammatory factors such as interferon gamma (IFN\u03b3) and granulocyte\u2013macrophage colony-stimulating factor (GM-CSF) at the maternal\u2013fetal interface have detrimental effects on trophoblast function and differentiation. This study demonstrates how the IL-6 cytokine family member oncostatin M (OSM) and STAT3 activation regulate trophoblast fusion and endocrine function in response to pro-inflammatory stress induced by IFN\u03b3 and GM-CSF. Using human cytotrophoblast-like BeWo (CT\/BW) cells, differentiated in villous syncytiotrophoblast (VST\/BW) cells, we show that beta-human chorionic gonadotrophin (\u03b2hCG) production and cell fusion process are affected in response to IFN\u03b3 or GM-CSF. However, those effects are abrogated with OSM by modulating the activation of IFN\u03b3-STAT1 and GM-CSF-STAT5 signaling pathways. OSM stimulation enhances the expression of STAT3, the phosphorylation of STAT3 and SMAD2, and the induction of negative regulators of inflammation (e.g., IL-10 and TGF\u03b21) and cytokine signaling (e.g., SOCS1 and SOCS3). Using STAT3-deficient VST\/BW cells, we show that STAT3 expression is required for OSM to regulate the effects of IFN\u03b3 in \u03b2hCG and E-cadherin expression. In contrast, OSM retains its modulatory effect on GM-CSF-STAT5 pathway activation even in STAT3-deficient VST\/BW cells, suggesting that OSM uses STAT3-dependent and -independent mechanisms to modulate the activation of pro-inflammatory pathways IFN\u03b3-STAT1 and GM-CSF-STAT5. Moreover, STAT3 deficiency in VST\/BW cells leads to the production of both a large amount of \u03b2hCG and an enhanced expression of activated STAT5 induced by GM-CSF, independently of OSM, suggesting a key role for STAT3 in \u03b2hCG production and trophoblast differentiation through STAT5 modulation. In conclusion, our study describes for the first time the critical role played by OSM and STAT3 signaling pathways to preserve and regulate trophoblast biological functions during inflammatory stress.<\/jats:p>","DOI":"10.3390\/cells13030229","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T06:54:12Z","timestamp":1706165652000},"page":"229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Oncostatin M and STAT3 Signaling Pathways Support Human Trophoblast Differentiation by Inhibiting Inflammatory Stress in Response to IFN\u03b3 and GM-CSF"],"prefix":"10.3390","volume":"13","author":[{"given":"Marion","family":"Ravelojaona","sequence":"first","affiliation":[{"name":"Groupe de Recherche en Signalisation Cellulaire (GRSC), D\u00e9partement de Biologie M\u00e9dicale, Universit\u00e9 du Qu\u00e9bec \u00e0 Trois-Rivi\u00e8res, 3351 Boul. des Forges, Trois-Rivi\u00e8res, QC G8Z 4M3, Canada"},{"name":"Centre de Recherche Interuniversitaire en Reproduction et D\u00e9veloppement-R\u00e9seau Qu\u00e9b\u00e9cois en Reproduction (CIRD-RQR), Universit\u00e9 de Montr\u00e9al, St-Hyacinthe, QC J2S 2M2, Canada"},{"name":"Regroupement Intersectoriel de Recherche en Sant\u00e9 de l\u2019Universit\u00e9 du Qu\u00e9bec (RISUQ), Universit\u00e9 du Qu\u00e9bec, Qu\u00e9bec, QC G1K 9H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Girouard","sequence":"additional","affiliation":[{"name":"Groupe de Recherche en Signalisation Cellulaire (GRSC), D\u00e9partement de Biologie M\u00e9dicale, Universit\u00e9 du Qu\u00e9bec \u00e0 Trois-Rivi\u00e8res, 3351 Boul. des Forges, Trois-Rivi\u00e8res, QC G8Z 4M3, Canada"},{"name":"Centre de Recherche Interuniversitaire en Reproduction et D\u00e9veloppement-R\u00e9seau Qu\u00e9b\u00e9cois en Reproduction (CIRD-RQR), Universit\u00e9 de Montr\u00e9al, St-Hyacinthe, QC J2S 2M2, Canada"},{"name":"Regroupement Intersectoriel de Recherche en Sant\u00e9 de l\u2019Universit\u00e9 du Qu\u00e9bec (RISUQ), Universit\u00e9 du Qu\u00e9bec, Qu\u00e9bec, QC G1K 9H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle Stella","family":"Kana Tsapi","sequence":"additional","affiliation":[{"name":"Groupe de Recherche en Signalisation Cellulaire (GRSC), D\u00e9partement de Biologie M\u00e9dicale, Universit\u00e9 du Qu\u00e9bec \u00e0 Trois-Rivi\u00e8res, 3351 Boul. des Forges, Trois-Rivi\u00e8res, QC G8Z 4M3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Chambers","sequence":"additional","affiliation":[{"name":"Medical School, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0543-6244","authenticated-orcid":false,"given":"Cathy","family":"Vaillancourt","sequence":"additional","affiliation":[{"name":"Centre de Recherche Interuniversitaire en Reproduction et D\u00e9veloppement-R\u00e9seau Qu\u00e9b\u00e9cois en Reproduction (CIRD-RQR), Universit\u00e9 de Montr\u00e9al, St-Hyacinthe, QC J2S 2M2, Canada"},{"name":"Regroupement Intersectoriel de Recherche en Sant\u00e9 de l\u2019Universit\u00e9 du Qu\u00e9bec (RISUQ), Universit\u00e9 du Qu\u00e9bec, Qu\u00e9bec, QC G1K 9H7, Canada"},{"name":"Centre Armand Frappier Sant\u00e9 Biotechnologie, Institut National de la Recherche Scientifique (INRS), Laval, QC H7V 1B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Van Themsche","sequence":"additional","affiliation":[{"name":"Groupe de Recherche en Signalisation Cellulaire (GRSC), D\u00e9partement de Biologie M\u00e9dicale, Universit\u00e9 du Qu\u00e9bec \u00e0 Trois-Rivi\u00e8res, 3351 Boul. des Forges, Trois-Rivi\u00e8res, QC G8Z 4M3, Canada"},{"name":"Centre de Recherche Interuniversitaire en Reproduction et D\u00e9veloppement-R\u00e9seau 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Reproduction et D\u00e9veloppement-R\u00e9seau Qu\u00e9b\u00e9cois en Reproduction (CIRD-RQR), Universit\u00e9 de Montr\u00e9al, St-Hyacinthe, QC J2S 2M2, Canada"},{"name":"Regroupement Intersectoriel de Recherche en Sant\u00e9 de l\u2019Universit\u00e9 du Qu\u00e9bec (RISUQ), Universit\u00e9 du Qu\u00e9bec, Qu\u00e9bec, QC G1K 9H7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1146\/annurev-cellbio-100814-125620","article-title":"Placenta: The forgotten organ","volume":"31","author":"Maltepe","year":"2015","journal-title":"Annu. 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