Spermidine Prevents Heart Injury in Neonatal Rats Exposed to Intrauterine Hypoxia by Inhibiting Oxidative Stress and Mitochondrial Fragmentation

Intrauterine hypoxia (IUH) is a common intrauterine dysplasia that can cause programming of the offspring cardiovascular system. In this study, we hypothesized that placental treatment with spermidine (SPD) can prevent heart injury in neonatal offspring exposed to IUH. Pregnant rats were exposed to...

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Bibliographic Details
Published in:Oxidative medicine and cellular longevity 2019-01, Vol.2019 (2019), p.1-14
Main Authors: Zhao, Yajun, Nikolaevna, Sazonova Elena, Wang, Lina, Lin, Yan, Liu, Yan, Yu, Xue, Li, Lingxu, Zhang, Hao, Chai, Nannan, Yan, Jiamin
Format: Article
Language:English
Subjects:
Animals
Cardiology
Dysplasia
Enzyme inhibitors
Female
Gene expression
Heart
Humidity
Hypoxia
Hypoxia - drug therapy
Male
Metabolism
Mitochondria
Mitochondria - drug effects
Mitochondrial DNA
Neurosciences
Oxidative stress
Oxidative Stress - drug effects
Physiology
Polyamines
Pregnancy
Rats
Rats, Wistar
Rodents
Sleep
Spermidine - pharmacology
Spermidine - therapeutic use
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Summary:Intrauterine hypoxia (IUH) is a common intrauterine dysplasia that can cause programming of the offspring cardiovascular system. In this study, we hypothesized that placental treatment with spermidine (SPD) can prevent heart injury in neonatal offspring exposed to IUH. Pregnant rats were exposed to 21% O2 or 10% O2 (hypoxia) for 7 days prior to term or were exposed to hypoxia and intraperitoneally administered SPD or SPD+difluromethylornithine (DFMO) on gestational days 15-21. Seven-day-old offspring were then sacrificed to assess several parameters. Our results demonstrated that IUH led to decreased myocardial ornithine decarboxylase (ODC) and increased spermidine/spermine N1-acetyltransferase (SSAT) expression in the offspring. IUH also resulted in decreased offspring body weight, heart weight, cardiomyocyte proliferation, and antioxidant capacity and increased cardiomyocyte apoptosis and fibrosis. Furthermore, IUH caused mitochondrial structure abnormality, dysfunction, and decreased biogenesis and led to a fission/fusion imbalance in offspring hearts. In vitro, hypoxia induced mitochondrial ROS accumulation, decreased membrane potential, and increased fragmentation. Notably, all hypoxia-induced changes analyzed in this study were prevented by SPD. Thus, in utero SPD treatment is a potential strategy for preventing IUH-induced neonatal cardiac injury.
ISSN:1942-0900
1942-0994
DOI:10.1155/2019/5406468