Women with pre‐gestational diabetes have a higher risk of producing children with congenital heart defects (CHDs), caused predominantly by hyperglycemia‐induced oxidative stress. In this study, we evaluated if exercise during pregnancy could mitigate oxidative stress and reduce the incidence of CHDs in the offspring of diabetic mice. Female mice were treated with streptozotocin to induce pre‐gestational diabetes, then mated with healthy males to produce offspring. They were also given access to running wheels 1 week before mating and allowed to exercise voluntarily until E18.5. Heart morphology, gene expression, and oxidative stress were assessed in foetal hearts. Maternal voluntary exercise results in a significantly lower incidence of CHDs from 59.5% to 25%. Additionally, diabetes‐induced defects in coronary artery and capillary morphogenesis were also lower with exercise. Myocardial cell proliferation and epithelial‐mesenchymal transition at E12.5 was significantly lower with pre‐gestational diabetes which was mitigated with maternal exercise. Cardiac gene expression of Notch1 , Snail1 , Gata4 and Cyclin D1 was significantly higher in the embryos of diabetic mice that exercised compared to the non‐exercised group. Furthermore, maternal exercise produced lower reactive oxygen species (ROS) and oxidative stress in the foetal heart. In conclusion, maternal exercise mitigates ROS and oxidative damage in the foetal heart, and results in a lower incidence of CHDs in the offspring of pre‐gestational diabetes. Exercise may be an effective intervention to compliment clinical management and further minimize CHD risk in mothers with diabetes.

BackgroundThe small GTPase Rac1 regulates diverse cellular functions, including both apicobasal and planar cell polarity pathways; however, its role in cardiac outflow tract (OFT) development remains unknown. In the present study, we aimed to examine the role of Rac1 in the anterior second heart field (SHF) splanchnic mesoderm and subsequent OFT development during heart morphogenesis.Methods and ResultsUsing the Cre/loxP system, mice with an anterior SHF‐specific deletion of Rac1 (Rac1 SHF) were generated. Embryos were collected at various developmental time points for immunostaining and histological analysis. Intrauterine echocardiography was also performed to assess aortic valve blood flow in embryos at embryonic day 18.5. The Rac1 SHF splanchnic mesoderm exhibited disruptions in SHF progenitor cellular organization and proliferation. Consequently, this led to a spectrum of OFT defects along with aortic valve defects in Rac1 SHF embryos. Mechanistically, it was found that the ability of the Rac1 SHF OFT myocardial cells to migrate into the proximal OFT cushion was severely reduced. In addition, expression of the neural crest chemoattractant semaphorin 3c was decreased. Lineage tracing showed that anterior SHF contribution to the OFT myocardium and aortic valves was deficient in Rac1 SHF hearts. Furthermore, functional analysis with intrauterine echocardiography at embryonic day 18.5 showed aortic valve regurgitation in Rac1 SHF hearts, which was not seen in control hearts.ConclusionsDisruptions of Rac1 signaling in the anterior SHF results in aberrant progenitor cellular organization and defects in OFT development. Our data show Rac1 signaling to be a critical regulator of cardiac OFT formation during embryonic heart development.

Background: Left ventricular noncompaction (LVNC) is a cardiomyopathy that can lead to arrhythmias, embolic events and heart failure. Despite our current knowledge of cardiac development, the mechanisms underlying noncompaction of the ventricular myocardium are still poorly understood. The small GTPase Rac1 acts as a crucial regulator of numerous developmental events. The present study aimed to investigate the cardiomyocyte specific role of Rac1 in embryonic heart development. Methods and Results: The Nkx2.5-Cre transgenic mice were crossed with Rac1f/f mice to generate mice with a cardiomyocyte specific deletion of Rac1 (Rac1Nkx2.5) during heart development. Embryonic Rac1Nkx2.5 hearts at E12.5–E18.5 were collected for histological analysis. Overall, Rac1Nkx2.5 hearts displayed a bifid apex, along with hypertrabeculation and a thin compact myocardium. Rac1Nkx2.5 hearts also exhibited ventricular septal defects (VSDs) and double outlet right ventricle (DORV) or overriding aorta. Cardiomyocytes had a rounded morphology and were highly disorganized, and the myocardial expression of Scrib, a planar cell polarity protein, was reduced in Rac1Nkx2.5 hearts. In addition, cell proliferation rate was significantly decreased in the Rac1Nkx2.5 ventricular myocardium at E9.5. Conclusions: Rac1 deficiency in the myocardium impairs cardiomyocyte elongation and organization, and proliferative growth of the heart. A spectrum of CHDs arises in Rac1Nkx2.5 hearts, implicating Rac1 signaling in the ventricular myocardium as a crucial regulator of OFT alignment, along with compact myocardium growth and development.

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Introduction: This study investigated the influence of clinical and psychosocial factors on medical students’ quality of life (QOL). Methods: A total of 408 medical students participated in this study. We collected data on participants’ sociodemographic details, symptoms of depression and Internet addiction, self-esteem, social support, and QOL. QOL was assessed using the World Health Organization Quality of Life-Abbreviated form (WHOQOL-BREF), which has four domains (physical health, psychological health, social relationships, and environment). A stepwise multiple linear regression model was constructed to identify factors’ independent impact on QOL. Results: Higher levels of depression and Internet addiction were associated with lower scores in all domains of QOL, whereas higher levels of self-esteem and social support were associated with higher scores. Being in third year versus first-year was associated with higher scores in the physical health and environment domains. Living alone or in dormitories, low or middle socioeconomic status, and insufficient or moderate pocket money were associated with lower scores in the environment domain. Additionally, female students displayed significantly lower scores for physical health, psychological health, and environment than male students, but not for social relationships. There were significant differences in certain domains of QOL due to sociodemographic factors. Discussion: This study demonstrates the clinical and psychosocial factors influencing medical students’ QOL. Educational strategies focusing on strengthening self-esteem and social support as well as preventing depression and Internet addiction may contribute to improving medical students’ QOL.