Diabetic Uterine Environment Leads to Disorders in Metabolism of Offspring.

Ming-Zhe Dong,Qing-Yuan Sun,Wei Shen,Li Li,Li-Hua Fan,Qian-Nan Li,Zhen-Bo Wang

doi:10.3389/fcell.2021.706879

Abstract

AimsResearch evidence indicates that epigenetic modifications of gametes in obese or diabetic parents may contribute to metabolic disorders in offspring. In the present study, we sought to address the effect of diabetic uterine environment on the offspring metabolism.MethodsType 2 diabetes mouse model was induced by high-fat diet combined with streptozotocin (STZ) administration. We maintained other effect factors constant and changed uterine environment by zygote transfers, and then determined and compared the offspring numbers, symptoms, body weight trajectories, and metabolism indices from different groups.ResultWe found that maternal type 2 diabetes mice had lower fertility and a higher dystocia rate, accompanying the increased risk of offspring malformations and death. Compared to only a pre-gestational exposure to hyperglycemia, exposure to hyperglycemia both pre- and during pregnancy resulted in offspring growth restriction and impaired metabolism in adulthood. But there was no significant difference between a pre-gestational exposure group and a no exposure group. The deleterious effects, no matter bodyweight or glucose tolerance, could be rescued by transferring the embryos from diabetic mothers into normal uterine environment.ConclusionOur data demonstrate that uterine environment of maternal diabetes makes critical impact on the offspring health.

Highlights

Diabetes is one of the largest global health emergencies of twenty-first century (Overland et al, 2014; Karuranga et al, 2019)
We still know little about the effects of maternal diabetes on the growth and metabolism of offspring and how to change this kind of susceptibility to prevent this destructive cycle of metabolic dysfunction through generations
We showed that embryo development was adversely affected by maternal diabetes, no evident imprinting abnormality was observed in oocytes from female offspring derived from a diabetic mother, and methylation in offspring’s oocytes is normal (Ge et al, 2013b)

Summary

Introduction

Diabetes is one of the largest global health emergencies of twenty-first century (Overland et al, 2014; Karuranga et al, 2019). Previous study has demonstrated that epigenetic inheritance via gametes by itself could increase an offspring’s susceptibility to develop to obesity and type 2 diabetes (Huypens et al, 2016). We have found that paternal prediabetes increases the susceptibility to diabetes in offspring through gametic epigenetic alterations (Wei et al, 2014). Other studies show that gestational diabetes may have effects on offspring (Fetita et al, 2006; Sasson et al, 2015). We still know little about the effects of maternal diabetes on the growth and metabolism of offspring and how to change this kind of susceptibility to prevent this destructive cycle of metabolic dysfunction through generations

Methods

Results

Conclusion