The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
J Pineal Res. 2016 Oct;61(3):340-52. doi: 10.1111/jpi.12351. Epub 2016 Jul 1.
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.
糖尿病妊娠的发病率不断上升，它会对胚胎发生产生不利影响，并增加成年后代血管代谢紊乱的风险。然而，目前尚不清楚母体糖尿病是否会增加后代成年后患心脏损伤的易感性。在这项研究中，我们观察到，在基线时，糖尿病小鼠的成年后代与非糖尿病小鼠的成年后代的心脏功能和结构没有差异。然而，与对照组相比，糖尿病母亲的后代在心肌缺血/再灌注（MIR）后，梗死面积增大，心功能障碍和心肌细胞凋亡增加，与线粒体和内质网（ER）应激介导的凋亡途径和氧化应激的过度激活有关。分子分析表明，糖尿病母亲后代心肌缺血耐受受损主要归因于心脏胰岛素受体底物（IRS）-1/Akt 信号通路的减弱。此外，还确定了母体褪黑素给药对后代对 MIR 反应的影响，结果表明，糖尿病孕鼠在怀孕期间给予褪黑素治疗可通过恢复心脏 IRS-1/Akt 信号通路显著改善其后代对 MIR 损伤的耐受。综上所述，这些数据表明，母体糖尿病使后代成年后患 MIR 损伤的风险增加，而糖尿病妊娠期间母体褪黑素的补充可能有助于改善后代的心肌缺血耐受。
