{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:35:18Z","timestamp":1791974118510,"version":"4.4.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Hydrogen sulfide is an endogenous gaseous signalling molecule with recognized roles in vascular regulation, redox homeostasis, and inflammation. In the placenta, H\n                      <jats:sub>2<\/jats:sub>\n                      S is essential for maintaining trophoblast function and promoting healthy vascular remodelling. Impaired H\n                      <jats:sub>2<\/jats:sub>\n                      S signalling has been implicated in placental disorders characterized by oxidative stress, particularly in preeclampsia. One of the principal drivers of oxidative stress in the placenta is H\/R injury, which mimics the intermittent perfusion patterns seen in early placental maldevelopment. Although the protective roles of H\n                      <jats:sub>2<\/jats:sub>\n                      S have been described in several ischemia-reperfusion models, its genome-wide transcriptional effects on trophoblasts under hypoxia\/reoxygenation-induced oxidative stress remain unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      HTR-8\/SVneo trophoblasts were subjected to H\/R injury induced by varying oxygen concentrations to model the fluctuating oxygen environments of early placental development, followed by treatment with an exogenous H\n                      <jats:sub>2<\/jats:sub>\n                      S donor (NaHS). A CSE inhibitor (PAG) treatment was also given. RNA sequencing was performed to characterize global gene expression changes. Differentially expressed genes were analyzed using KEGG and Gene Ontology enrichment, protein\u2013protein interaction network mapping, and transcription factor prediction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      H\/R induced extensive transcriptional remodelling, with robust activation of HIF-1, PI3K\u2013Akt, MAPK, Rap1\/Ras, NF-\u03baB, and focal adhesion pathways. H\/R [2\/10% O\n                      <jats:sub>2<\/jats:sub>\n                      ] triggered pronounced glycolytic, hypoxia-adaptive, anti-apoptotic, and pro-invasive signatures. NaHS modulated these responses in a context-dependent manner: it attenuated early chemokine-driven inflammation, enhanced angiogenic and ECM-remodelling programs, and strengthened metabolic adaptation under a higher hypoxic burden 2\/10% H\/R paradigm. PAG induced a chronic inflammatory angiogenic signature, indicating endogenous H\n                      <jats:sub>2<\/jats:sub>\n                      S restrains basal inflammatory activation. Integrated regulation of proliferation, migration, apoptosis, morphogenesis, and angiogenesis was observed through biological process analysis, with major changes noticed in NaHS-treated 2\/10% H\/R conditions. JUN, PTGS2, MAP3K5, DUSP1, SFN, NCF2, THBS2, and GADD45A emerged as the central interconnected hub-gene module through PPI analysis. Among these, JUN and PTGS2 appeared as potential integrators of trophoblast remodelling, redox stress, and inflammatory signalling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our study provides the first evidence of transcriptomic analysis showing that H\n                      <jats:sub>2<\/jats:sub>\n                      S alters gene networks in trophoblast cells subjected to H\/R-induced oxidative stress. The results highlight coordinated regulation of metabolic, angiogenic, and inflammatory pathways, providing fundamental understanding into how H\n                      <jats:sub>2<\/jats:sub>\n                      S may influence trophoblast adaptation to stress.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2026.1785302","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:27:25Z","timestamp":1781584045000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Hydrogen sulfide modulates gene networks in hypoxia\/reoxygenation-stressed trophoblasts: insights from transcriptome profiling"],"prefix":"10.3389","volume":"6","author":[{"family":"Shivani","sequence":"first","affiliation":[{"name":"Department of Anatomy, All India Institute of Medical Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Katiyar","sequence":"additional","affiliation":[{"name":"Bioinformatics Facility, Centralized Core Research Facility, All India Institute of Medical Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil Kumar","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Anatomy, All India Institute of Medical Sciences","place":["New Delhi, India"]},{"name":"Department of Anatomy, ASMC Kushinagar","place":["Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pallavi","family":"Arora","sequence":"additional","affiliation":[{"name":"Department of Anatomy, All India Institute of Medical Sciences","place":["New Delhi, India"]},{"name":"Department of Anatomy, Shri Mata Vaishno Devi Institute of Medical Excellence","place":["Kakryal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Kumari","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, All India Institute of Medical Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tooba Tahreem","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Anatomy, All India Institute of Medical Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pallavi","family":"Kshetrapal","sequence":"additional","affiliation":[{"name":"Lab of Perinatal Research, BRIC-Translational Health Science and Technology Institute","place":["Faridabad, Haryana, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renu","family":"Dhingra","sequence":"additional","affiliation":[{"name":"Department of Anatomy, All India Institute of Medical Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"D789","DOI":"10.1093\/nar\/gku1205","article-title":"OMIM.org: Online mendelian inheritance in man (OMIM\u00ae), an online catalog of human genes and genetic disorders","volume":"43","author":"Amberger","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1101\/002824","article-title":"HTSeq \u2013 a python framework to work with high-throughput sequencing data","author":"Anders","year":"2014","journal-title":"Bioinformatics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.3390\/ijms19051496","article-title":"Oxidative stress in preeclampsia and placental diseases","volume":"19","author":"Aouache","year":"2018","journal-title":"IJMS"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1384214","DOI":"10.3389\/fmolb.2024.1384214","article-title":"Analyzing molecular signatures in preeclampsia and fetal growth restriction: identifying key genes, pathways, and therapeutic targets for preterm birth","volume":"11","author":"Azmi","year":"2024","journal-title":"Front. 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