{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:44:31Z","timestamp":1790239471554,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T00:00:00Z","timestamp":1615507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Physiological oxygen tension rises dramatically in the placenta between 8 and 14 weeks of gestation. Abnormalities in this period can lead to gestational diseases, whose underlying mechanisms remain unclear. We explored the changes at mRNA level by comparing the transcriptomes of human placentas at 8\u201310 gestational weeks and 12\u201314 gestational weeks. A total of 20 samples were collected and divided equally into four groups based on sex and age. Cytotrophoblasts were isolated and sequenced using RNAseq. Key genes were identified using two different methods: DESeq2 and weighted gene co-expression network analysis (WGCNA). We also constructed a local database of known targets of hypoxia-inducible factor (HIF) subunits, alpha and beta, to investigate expression patterns likely linked with changes in oxygen. Patterns of gene enrichment in and among the four groups were analyzed based on annotations of gene ontology (GO) and KEGG pathways. We characterized the similarities and differences between the enrichment patterns revealed by the two methods and the two conditions (age and sex), as well as those associated with HIF targets. Our results provide a broad perspective of the processes that are active in cytotrophoblasts during the rise in physiological oxygen, which should benefit efforts to discover possible drug-targeted genes or pathways in the human placenta.<\/jats:p>","DOI":"10.3390\/ijms22062901","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T11:56:55Z","timestamp":1615550215000},"page":"2901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Age and Sex-Related Changes in Human First-Trimester Placenta Transcriptome and Insights into Adaptative Responses to Increased Oxygen"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0072-0847","authenticated-orcid":false,"given":"Fulin","family":"Liu","sequence":"first","affiliation":[{"name":"Pathophysiology &amp; Pharmacotoxicology of the Human Placenta, Pre &amp; Postnatal Microbiota, Universit\u00e9 de Paris, INSERM, 3PHM, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Simasotchi","sequence":"additional","affiliation":[{"name":"Pathophysiology &amp; Pharmacotoxicology of the Human Placenta, Pre &amp; Postnatal Microbiota, Universit\u00e9 de Paris, INSERM, 3PHM, F-75006 Paris, France"},{"name":"Fondation PremUp, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Vibert","sequence":"additional","affiliation":[{"name":"Pathophysiology &amp; Pharmacotoxicology of the Human Placenta, Pre &amp; Postnatal Microbiota, Universit\u00e9 de Paris, INSERM, 3PHM, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencan","family":"Zhu","sequence":"additional","affiliation":[{"name":"UMR Applied Mathematics &amp; Informatics, AgroParisTech-Universit\u00e9 Paris-Saclay, F-75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Gil","sequence":"additional","affiliation":[{"name":"Pathophysiology &amp; Pharmacotoxicology of the Human Placenta, Pre &amp; Postnatal Microbiota, Universit\u00e9 de Paris, INSERM, 3PHM, F-75006 Paris, France"},{"name":"Fondation PremUp, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6263-4875","authenticated-orcid":false,"given":"S\u00e9verine A.","family":"Degrelle","sequence":"additional","affiliation":[{"name":"Pathophysiology &amp; Pharmacotoxicology of the Human Placenta, Pre &amp; Postnatal Microbiota, Universit\u00e9 de Paris, INSERM, 3PHM, F-75006 Paris, France"},{"name":"Inovarion, F-75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Fournier","sequence":"additional","affiliation":[{"name":"Pathophysiology &amp; Pharmacotoxicology of the Human Placenta, Pre &amp; Postnatal Microbiota, Universit\u00e9 de Paris, INSERM, 3PHM, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1007\/s00018-014-1794-x","article-title":"Signaling pathways in mouse and human trophoblast differentiation: A comparative review","volume":"72","author":"Soncin","year":"2015","journal-title":"Cell. 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