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The risk of ETI to foetuses remain unknown. Thus the effect of maternally administered ETI on foetal genetic and structural development was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Pregnant Sprague Dawley rats were orally treated with ETI (6.7\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup> elexacaftor\u2009+\u20093.5\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup> tezacaftor\u2009+\u200925\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup> ivacaftor) for 7\u00a0days from E12 to E19. Tissue samples collected at E19 were analysed using histology and RNA sequencing. Histological changes and differentially expressed genes (DEG) were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>No overt structural abnormalities were found in foetal pancreas, liver, lung and small intestine after 7\u2010day ETI exposure. Very few non\u2010functionally associated DEG in foetal liver, lung and small intestine were identified using RNA\u2010seq. 29 DEG were identified in thymus (27 up\u2010regulated and two down\u2010regulated) and most were functionally linked to each other. Gene ontology enrichment analysis revealed that multiple muscle\u2010related terms were significantly enriched. Many more DEG were identified in cortex (44 up\u2010regulated and four down\u2010regulated) and a group of these were involved in central nervous system and brain development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implication<\/jats:title><jats:p>Sub\u2010chronic ETI treatment in late pregnancy does not appear to pose a significant risk to the genetic and structural development of many foetal tissues. However, significant gene changes in foetal thymic myoid cells and cortical neuronal development requires future follow\u2010up studies to assess the risk to these organs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16417","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T12:00:26Z","timestamp":1716292826000},"page":"2413-2428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Extent of foetal exposure to maternal elexacaftor\/tezacaftor\/ivacaftor during pregnancy"],"prefix":"10.1111","volume":"181","author":[{"given":"Danni","family":"Li","sequence":"first","affiliation":[{"name":"Department of Biochemistry &amp; Pharmacology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences The University of Melbourne  Parkville VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Donnelley","sequence":"additional","affiliation":[{"name":"Robinson Research Institute University of Adelaide  Adelaide South Australia Australia"},{"name":"Adelaide Medical School University of Adelaide  Adelaide South Australia Australia"},{"name":"Department of Respiratory and Sleep Medicine Women's and Children's Hospital  North Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Parsons","sequence":"additional","affiliation":[{"name":"Robinson Research Institute University of Adelaide  Adelaide South Australia Australia"},{"name":"Adelaide Medical School University of Adelaide  Adelaide South Australia Australia"},{"name":"Department of Respiratory and Sleep Medicine Women's and Children's Hospital  North Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Habgood","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Pharmacology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences The University of Melbourne  Parkville VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6044-4824","authenticated-orcid":false,"given":"Elena K.","family":"Schneider\u2010Futschik","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Pharmacology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences The University of Melbourne  Parkville VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00092"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16178"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093133"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2004.01.004"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(19)30337-6"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004280050178"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14081674"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2021.12.004"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_14_11_1","unstructured":"European Medicines Agency. 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