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While the molecular mechanisms leading to increased ICM cell numbers and pluripotency gene expression under hypoxia have been deciphered, it remains unknown which regulatory pathways caused the underweight fetal body and overweight placenta after maternal exposure to hyperbaric oxygen (HBO).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The blastocysts from the HBO\u2010exposed pregnant mice revealed significantly increased signals of reactive oxygen species (ROS) and nuclear Nrf2 staining, decreased Nf2 and Oct4 expression, increased nuclear Tp53bp1 and active caspase\u20103 staining, and ectopic nuclear signals of Cdx2, Yap, and the Notch1 intracellular domain (N1ICD) in the ICM. In the ICM of the HBO\u2010exposed blastocysts, both <jats:italic>Nf2<\/jats:italic> cDNA microinjection and <jats:italic>Nrf2<\/jats:italic> shRNA microinjection significantly decreased the ectopic nuclear expression of Cdx2, Tp53bp1, and Yap whereas increased Oct4 expression, while <jats:italic>Nrf2<\/jats:italic> shRNA microinjection also significantly decreased <jats:italic>Notch1<\/jats:italic> mRNA levels and nuclear expression of N1ICD and active caspase\u20103.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We show for the first time that maternal exposure to HBO at the preimplantation stage induces apoptosis and impairs ICM cell specification via upregulating <jats:italic>Nrf2<\/jats:italic>\u2010<jats:italic>Notch1\u2010Cdx2<\/jats:italic> expression and downregulating <jats:italic>Nf2<\/jats:italic>\u2010<jats:italic>Oct4<\/jats:italic> expression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.671","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T09:28:56Z","timestamp":1697621336000},"page":"467-489","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Maternal exposure to hyperbaric oxygen at the preimplantation stages increases apoptosis and ectopic Cdx2 expression and decreases Oct4 expression in mouse blastocysts via <scp><i>Nrf2<\/i>\u2010<i>Notch1<\/i><\/scp> upregulation and <i>Nf2<\/i> downregulation"],"prefix":"10.1002","volume":"253","author":[{"given":"Yu\u2010Ming","family":"Li","sequence":"first","affiliation":[{"name":"Department of Integrative Immunobiology Duke University School of Medicine  Durham North Carolina USA"},{"name":"Department of Internal Medicine Taichung Veterans General Hospital  Taichung City Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu 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