Diabetes is a chronic disease. There is currently no cure. It requires long-term adjustment of diet, living habits and drug control to maintain normal blood sugar. Therefore, early prevention of diabetes has become an important public health issue. It is known that having a family history of diabetes, or having gestational diabetes when the mother is pregnant, is a risk factor for developing diabetes.
A recent paper published in “Nature”, more from the perspective of epigenetics, pointed out that pre-pregnancy exposure to high blood sugar environment will make oocyte DNA experienceMethylation modification, thereby increasing the risk of developing chronic diabetes in young children. This study, published by Zhejiang University School of Medicine in China, brings a new perspective on diabetes prevention and control, which is different from gestational diabetes risk factors. This study shows that by controlling the blood sugar environment in the mother’s body before pregnancy, diabetes can be fundamentally prevented in the offspring.
High blood sugar environment increases the risk of diabetes in offspring
In order to understand how pre-pregnancy environmental factors in women change the probability of developing diabetes in offspring, Dr. Huang Hefeng’s research team from Zhejiang Medical College established a female mouse model to exclude the continuous impact of hyperglycemia on embryonic and fetal development. In vitro fertilization, and the embryos are transferred into healthy mice to grow into offspring and observe whether their metabolic characteristics are abnormal.
It was found that the offspring showed symptoms of glucose intolerance (impaired glucose tolerance), that is, a high blood sugar environment increased the offspring’s susceptibility to chronic diabetes. The research team further proposed a more in-depth molecular mechanism to explain the reason for the increased incidence of offspring.
Oocyte methylation modification is the culprit
The reason why the offspring of mice are prone to diabetes is due to the lack of TET3 (TET methylcytosine dioxygenase 3) protein in the oocytes of the mother mouse. TET3 is related to the regulatory mechanism of chronic disease. The team pointed out that the high blood sugar environment in female mice can cause insufficient TET3 concentration, which in turn leads to insufficient demethylation or hypermethylation of fertilized eggs.
As for the association between TET3 deficiency and abnormal insulin secretion, another important gene is involved GCK（glucokinase gene）。GCK Involved in insulin secretion, caused by hypermethylation during zygote replication and division GCK Low gene expression, together with insufficient insulin secretion, increases the susceptibility of offspring to diabetes as they age.
Pre-pregnancy blood sugar control is a new strategy for diabetes prevention and treatment
Not only was this study confirmed in a mouse model, but the clinical manifestations of some pregnant women with diabetes also support this hypothesis. The team obtained samples of immature oocytes from diabetic patients from Hangzhou and Shanghai hospitals in China, and also found that TET3 protein deficiency,GCK The phenomenon of low gene expression.
This study is different from the previous focus on the risk factors of gestational diabetes in pregnant women, and more importantly, it points out that the pre-pregnancy blood sugar environment can bring disease risk through epigenetic modification. Professor Huang Hefeng, the project host, said that the transgenerational genetic phenomenon caused by the reproductive environment provides a new intervention strategy for the prevention and control of chronic diabetes.
References:
1/ Nature, 2022; https://www.nature.com/articles/s41586-022-04756-4
©www.geneonline.news. All rights reserved. Geneonline is copyrighted and may not be reproduced without authorization. For cooperation, please contact: service@geneonlineasia.com
