{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T20:44:11Z","timestamp":1788986651419,"version":"build-2803163510"},"reference-count":62,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:00:00Z","timestamp":1614384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["NIH-NIGMS CoBRE 2P20GM103620-06"],"award-info":[{"award-number":["NIH-NIGMS CoBRE 2P20GM103620-06"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["NIH-NIGMS CoBRE P20GM103548"],"award-info":[{"award-number":["NIH-NIGMS CoBRE P20GM103548"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["NIH-NICHD K08 HD078504"],"award-info":[{"award-number":["NIH-NICHD K08 HD078504"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Offspring born to diabetic or obese mothers have a higher lifetime risk of heart disease. Previously, we found that rat offspring exposed to late-gestational diabetes mellitus (LGDM) and maternal high-fat (HF) diet develop mitochondrial dysfunction, impaired cardiomyocyte bioenergetics, and cardiac dysfunction at birth and again during aging. Here, we compared echocardiography, cardiomyocyte bioenergetics, oxidative damage, and mitochondria-mediated cell death among control, pregestational diabetes mellitus (PGDM)-exposed, HF-diet-exposed, and combination-exposed newborn offspring. We hypothesized that PGDM exposure, similar to LGDM, causes mitochondrial dysfunction to play a central, pathogenic role in neonatal cardiomyopathy. We found that PGDM-exposed offspring, similar to LGDM-exposed offspring, have cardiac dysfunction at birth, but their isolated cardiomyocytes have seemingly less bioenergetics impairment. This finding was due to confounding by impaired viability related to poorer ATP generation, more lipid peroxidation, and faster apoptosis under metabolic stress. To mechanistically isolate and test the role of mitochondria, we transferred mitochondria from normal rat myocardium to control and exposed neonatal rat cardiomyocytes. As expected, transfer provides a respiratory boost to cardiomyocytes from all groups. They also reduce apoptosis in PGDM-exposed males, but not in females. Findings highlight sex-specific differences in mitochondria-mediated mechanisms of developmentally programmed heart disease and underscore potential caveats of therapeutic mitochondrial transfer.<\/jats:p>","DOI":"10.3390\/ijms22052382","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T20:55:44Z","timestamp":1614459344000},"page":"2382","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational Diabetes"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8741-2240","authenticated-orcid":false,"given":"Eli J.","family":"Louwagie","sequence":"first","affiliation":[{"name":"Sanford School of Medicine, University of South Dakota, Sioux Falls, SD 57105, USA"},{"name":"Environmental Influences on Health and Disease Group, Sanford Research, Sioux Falls, SD 57104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9015-3929","authenticated-orcid":false,"given":"Tricia D.","family":"Larsen","sequence":"additional","affiliation":[{"name":"Environmental Influences on Health and Disease Group, Sanford Research, Sioux Falls, SD 57104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela L.","family":"Wachal","sequence":"additional","affiliation":[{"name":"Environmental Influences on Health and Disease Group, Sanford Research, Sioux Falls, SD 57104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler C.T.","family":"Gandy","sequence":"additional","affiliation":[{"name":"Environmental Influences on Health and Disease Group, Sanford Research, Sioux Falls, SD 57104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5966-669X","authenticated-orcid":false,"given":"Michelle L.","family":"Baack","sequence":"additional","affiliation":[{"name":"Sanford School of Medicine, University of South Dakota, Sioux Falls, SD 57105, USA"},{"name":"Environmental Influences on Health and Disease Group, Sanford Research, Sioux Falls, SD 57104, USA"},{"name":"Boekelheide Neonatal Intensive Care Unit, Sanford Children\u2019s Hospital, Sioux Falls, SD 57117, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,27]]},"reference":[{"key":"ref_1","unstructured":"Weisman, L.E., Wolfsdorf, J.I., and Kim, M.S. 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