PMID- 37686430 OWN - NLM STAT- MEDLINE DCOM- 20230911 LR - 20230911 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 17 DP - 2023 Sep 3 TI - Sex-Specific Effects of Prenatal Hypoxia and a Placental Antioxidant Treatment on Cardiac Mitochondrial Function in the Young Adult Offspring. LID - 10.3390/ijms241713624 [doi] LID - 13624 AB - Prenatal hypoxia is associated with placental oxidative stress, leading to impaired fetal growth and an increased risk of cardiovascular disease in the adult offspring; however, the mechanisms are unknown. Alterations in mitochondrial function may result in impaired cardiac function in offspring. In this study, we hypothesized that cardiac mitochondrial function is impaired in adult offspring exposed to intrauterine hypoxia, which can be prevented by placental treatment with a nanoparticle-encapsulated mitochondrial antioxidant (nMitoQ). Cardiac mitochondrial respiration was assessed in 4-month-old rat offspring exposed to prenatal hypoxia (11% O(2)) from gestational day (GD)15-21 receiving either saline or nMitoQ on GD 15. Prenatal hypoxia did not alter cardiac mitochondrial oxidative phosphorylation capacity in the male offspring. In females, the NADH + succinate pathway capacity decreased by prenatal hypoxia and tended to be increased by nMitoQ. Prenatal hypoxia also decreased the succinate pathway capacity in females. nMitoQ treatment increased respiratory coupling efficiency in prenatal hypoxia-exposed female offspring. In conclusion, prenatal hypoxia impaired cardiac mitochondrial function in adult female offspring only, which was improved with prenatal nMitoQ treatment. Therefore, treatment strategies targeting placental oxidative stress in prenatal hypoxia may reduce the risk of cardiovascular disease in adult offspring by improving cardiac mitochondrial function in a sex-specific manner. FAU - Chatterjee, Paulami AU - Chatterjee P AD - Department of Physiology, University of Alberta, Edmonton, AB T6G 2R3, Canada. AD - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2R3, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada. FAU - Holody, Claudia D AU - Holody CD AUID- ORCID: 0000-0003-1479-3809 AD - Faculty Saint-Jean, University of Alberta, Edmonton, AB T6G 2R3, Canada. AD - Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, Canada. FAU - Kirschenman, Raven AU - Kirschenman R AUID- ORCID: 0000-0001-9310-8384 AD - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2R3, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada. FAU - Graton, Murilo E AU - Graton ME AD - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2R3, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada. FAU - Spaans, Floor AU - Spaans F AUID- ORCID: 0000-0002-8024-4413 AD - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2R3, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada. FAU - Phillips, Tom J AU - Phillips TJ AD - UK Dementia Research Institute, Cardiff University, Cardiff CF10 3AT, UK. FAU - Case, C Patrick AU - Case CP AD - Musculoskeletal Research Unit, University of Bristol, Bristol BS10 5NB, UK. FAU - Bourque, Stephane L AU - Bourque SL AUID- ORCID: 0000-0001-6375-7404 AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada. AD - Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, Canada. AD - Department of Anesthesiology & Pain Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada. FAU - Lemieux, Helene AU - Lemieux H AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada. AD - Faculty Saint-Jean, University of Alberta, Edmonton, AB T6G 2R3, Canada. AD - Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada. FAU - Davidge, Sandra T AU - Davidge ST AUID- ORCID: 0000-0002-5559-4905 AD - Department of Physiology, University of Alberta, Edmonton, AB T6G 2R3, Canada. AD - Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2R3, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, AB T6G 2R3, Canada. LA - eng GR - FS154313/CAPMC/CIHR/Canada PT - Journal Article DEP - 20230903 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antioxidants) RN - 0 (Vitamins) RN - 0 (Succinates) SB - IM MH - Female MH - Male MH - Pregnancy MH - Animals MH - Rats MH - *Antioxidants/pharmacology/therapeutic use MH - *Cardiovascular Diseases MH - Placenta MH - Vitamins MH - Hypoxia/complications/drug therapy MH - Mitochondria MH - Succinates PMC - PMC10487956 OTO - NOTNLM OT - cardiac OT - developmental origins of health and disease (DOHaD) OT - mitochondria OT - nMitoQ treatment OT - offspring OT - oxidative phosphorylation (OXPHOS) OT - prenatal hypoxia COIS- The authors declare no conflict of interest. EDAT- 2023/09/09 11:47 MHDA- 2023/09/11 06:42 PMCR- 2023/09/03 CRDT- 2023/09/09 01:14 PHST- 2023/07/17 00:00 [received] PHST- 2023/08/25 00:00 [revised] PHST- 2023/09/01 00:00 [accepted] PHST- 2023/09/11 06:42 [medline] PHST- 2023/09/09 11:47 [pubmed] PHST- 2023/09/09 01:14 [entrez] PHST- 2023/09/03 00:00 [pmc-release] AID - ijms241713624 [pii] AID - ijms-24-13624 [pii] AID - 10.3390/ijms241713624 [doi] PST - epublish SO - Int J Mol Sci. 2023 Sep 3;24(17):13624. doi: 10.3390/ijms241713624.