The impaired myocardial ischemic tolerance in adult offspring of diabetic pregnancy is restored by maternal melatonin treatment.
Diabetic pregnancy, with ever increasing prevalence, adversely affects embryogenesis and increases vasculometabolic disorder risks in adult offspring. However, it remains poorly understood whether maternal diabetes increases the offspring's susceptibility to heart injuries in adulthood. In this study, we observed that cardiac function and structure were comparable between adult offspring born to diabetic mice and their counterparts born to nondiabetic mice at baseline. However, in response to myocardial ischemia/reperfusion (MIR), diabetic mother offspring exhibited augmented infarct size, cardiac dysfunction, and myocardial apoptosis compared with control, in association with exaggerated activation of mitochondria- and endoplasmic reticulum (ER) stress-mediated apoptosis pathways and oxidative stress. Molecular analysis showed that the impaired myocardial ischemic tolerance in diabetic mother offspring was mainly attributable to blunted cardiac insulin receptor substrate (IRS)-1/Akt signaling. Furthermore, the effect of maternal melatonin administration on offspring's response to MIR was determined, and the results indicated that melatonin treatment in diabetic dams during pregnancy significantly improved the tolerance to MIR injury in their offspring, via restoring cardiac IRS-1/Akt signaling. Taken together, these data suggest that maternal diabetes predisposes offspring to augmented MIR injury in adulthood, and maternal melatonin supplementation during diabetic pregnancy may hold promise for improving myocardial ischemic tolerance in the offspring.
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Ling
L
Gao
Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Yi-Chao
YC
Zhao
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Yan
Y
Liang
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Xian-Hua
XH
Lin
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Ya-Jing
YJ
Tan
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Dan-Dan
DD
Wu
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Xin-Zhu
XZ
Li
Department of Cardiology, The First Affiliated Hospital, School of Medicine, Wenzhou Medical University, Wenzhou, China.
Bo-Zhi
BZ
Ye
Department of Cardiology, The First Affiliated Hospital, School of Medicine, Wenzhou Medical University, Wenzhou, China.
Fan-Qi
FQ
Kong
The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.|Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China.
Jian-Zhong
JZ
Sheng
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. huanghefg@hotmail.com.|The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China. huanghefg@hotmail.com.|Institute of Embryo-Fetal Original Adult Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. huanghefg@hotmail.com.
He-Feng
HF
Huang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D019587:Dietary Supplements; D005260:Female; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000188:drug therapy* / Q000378:metabolism; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000517:prevention & control*
D008550:Melatonin
apoptosis; heart; insulin signaling; melatonin; oxidative stress; pregestational diabetes