PMID- 32749725 OWN - NLM STAT- MEDLINE DCOM- 20211020 LR - 20211214 IS - 1469-445X (Electronic) IS - 0958-0670 (Linking) VI - 105 IP - 9 DP - 2020 Sep TI - Placenta-targeted treatment in hypoxic dams improves maturation and growth of fetal cardiomyocytes in vitro via the release of placental factors. PG - 1507-1514 LID - 10.1113/EP088799 [doi] AB - NEW FINDINGS: What is the central question of this study? Does treatment of hypoxic dams with a placenta-targeted antioxidant prevent the release of placenta-derived factors that impair maturation or growth of fetal cardiomyocytes in vitro? What is the main finding and its importance? Factors released from hypoxic placentae impaired fetal cardiomyocyte maturation (induced terminal differentiation) and growth (increased cell size) in vitro, which was prevented by maternal treatment with a placenta-targeted antioxidant (nMitoQ). Moreover, there were no sex differences in the effects of placental factors on fetal cardiomyocyte maturation and growth. Overall, our data suggest that treatment targeted against placental oxidative stress could prevent fetal programming of cardiac diseases via the release of placental factors. ABSTRACT: Pregnancy complications associated with placental oxidative stress may impair fetal organ development through the release of placenta-derived factors into the fetal circulation. We assessed the effect of factors secreted from placentae previously exposed to prenatal hypoxia on fetal cardiomyocyte development and developed a treatment strategy that targets placental oxidative stress by encapsulating the antioxidant MitoQ into nanoparticles (nMitoQ). We used a rat model of prenatal hypoxia (gestational day (GD) 15-21), which was treated with saline or nMitoQ on GD15. On GD21, placentae were harvested, placed in culture, and conditioned medium (containing placenta-derived factors) was collected after 24 h. This conditioned medium was then added to cultured cardiomyocytes from control dam fetuses. Conditioned medium from prenatally hypoxic placentae increased the percentage of binucleated cardiomyocytes (marker of terminal differentiation) and the size of mononucleated and binucleated cardiomyocytes (sign of hypertrophy), effects that were prevented by nMitoQ treatment. Our data suggest that factors derived from placentae previously exposed to prenatal hypoxia lead to abnormal fetal cardiomyocyte development, and show that treatment against placental oxidative stress may prevent fetal programming of cardiac disease. CI - (c) 2020 The Authors. Experimental Physiology (c) 2020 The Physiological Society. FAU - Ganguly, Esha AU - Ganguly E AD - Department of Physiology, University of Alberta, Edmonton, Alberta, Canada. AD - Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Alberta, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada. FAU - Spaans, Floor AU - Spaans F AD - Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Alberta, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada. FAU - Morton, Jude S AU - Morton JS AD - Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Alberta, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada. FAU - Kirschenman, Raven AU - Kirschenman R AD - Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Alberta, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada. FAU - Aljunaidy, Mais M AU - Aljunaidy MM AD - Department of Physiology, University of Alberta, Edmonton, Alberta, Canada. AD - Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Alberta, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada. FAU - Phillips, Thomas E J AU - Phillips TEJ AD - Dementia Research Institute, Cardiff University, Cardiff, UK. FAU - Case, C Patrick AU - Case CP AD - Musculoskeletal Research Unit, University of Bristol, Bristol, UK. FAU - Cooke, Christy-Lynn M AU - Cooke CM AD - Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Alberta, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada. FAU - Davidge, Sandra T AU - Davidge ST AUID- ORCID: 0000-0002-5559-4905 AD - Department of Physiology, University of Alberta, Edmonton, Alberta, Canada. AD - Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Alberta, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada. LA - eng GR - FS 154313/CAPMC/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200814 PL - England TA - Exp Physiol JT - Experimental physiology JID - 9002940 RN - 0 (Antioxidants) RN - 0 (Culture Media, Conditioned) RN - 0 (Organophosphorus Compounds) RN - 1339-63-5 (Ubiquinone) RN - 47BYS17IY0 (mitoquinone) SB - IM MH - Animals MH - Antioxidants/*pharmacology MH - Cells, Cultured MH - Culture Media, Conditioned MH - Female MH - Fetal Development/*drug effects MH - Hypoxia/*drug therapy MH - Male MH - Myocytes, Cardiac/*physiology MH - Organophosphorus Compounds/pharmacology MH - Oxidative Stress MH - Placenta/*physiology MH - Pregnancy MH - Rats MH - Rats, Sprague-Dawley MH - Ubiquinone/analogs & derivatives/pharmacology OTO - NOTNLM OT - fetal cardiomyocyte OT - nMitoQ OT - placental factors EDAT- 2020/08/05 06:00 MHDA- 2021/10/21 06:00 CRDT- 2020/08/05 06:00 PHST- 2020/06/01 00:00 [received] PHST- 2020/07/31 00:00 [accepted] PHST- 2020/08/05 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2020/08/05 06:00 [entrez] AID - 10.1113/EP088799 [doi] PST - ppublish SO - Exp Physiol. 2020 Sep;105(9):1507-1514. doi: 10.1113/EP088799. Epub 2020 Aug 14.