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When disturbed, it leads to congenital cardiac anomalies that affect approximately 1% of live births. Genetic variants in several loci lead to anomalies, with the transcription factor <jats:italic>NKX2-5<\/jats:italic> being one of the largest. However, there are also non-genetic factors that influence cardiac malformations. We examined the hypothesis that hyperoxia may be beneficial and can rescue genetic cardiac anomalies induced by an <jats:italic>Nkx2-5<\/jats:italic> mutation. Intermittent mild hyperoxia (40% PO<jats:sub>2<\/jats:sub>) was applied for 10\u00a0h per day to normal wild-type female mice mated with heterozygous <jats:italic>Nkx2-5<\/jats:italic> mutant males from gestational day 8.5 to birth. Hyperoxia therapy reduced excessive trabeculation in <jats:italic>Nkx2-5<\/jats:italic> mutant mice compared to normoxic conditions (ratio of trabecular layer relative to compact layer area, normoxia 1.84\u2009\u00b1\u20090.07 vs. hyperoxia 1.51\u2009\u00b1\u20090.04) and frequency of muscular ventricular septal defects per heart (1.53\u2009\u00b1\u20090.32 vs. 0.68\u2009\u00b1\u20090.15); however, the incidence of membranous ventricular septal defects in <jats:italic>Nkx2-5<\/jats:italic> mutant hearts was not changed. <jats:italic>Nkx2-5<\/jats:italic> mutant embryonic hearts showed defective coronary vessel organization, which was improved by intermittent mild hyperoxia. The results of our study showed that mild gestational hyperoxia therapy rescued genetic cardiac malformation induced by <jats:italic>Nkx2-5<\/jats:italic> mutation in part.<\/jats:p>","DOI":"10.1038\/s41598-021-85569-9","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T11:04:44Z","timestamp":1616497484000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part"],"prefix":"10.1038","volume":"11","author":[{"given":"Cassandra F.","family":"Doll","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia J.","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa S.","family":"Hashimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tabor J.","family":"Grindrod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fariz F.","family":"Alkassis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence X.","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Una","family":"Milovanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana I.","family":"Sandino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideko","family":"Kasahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"85569_CR1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.ahj.2003.05.003","volume":"147","author":"JI Hoffman","year":"2004","unstructured":"Hoffman, J. 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