China News Service, Hangzhou, May 19 (Tong Xiaoyu Ke Yineng) On May 19, the reporter learned from Zhejiang University (hereinafter referred to as "Zhejiang University") that the research group of Huang Hefeng, honorary president of the Obstetrics and Gynecology Hospital affiliated to Zhejiang University School of Medicine In cooperation with Xu Guoliang's team at the Center for Excellence in Molecular and Cell Science of the Chinese Academy of Sciences, a new mechanism for the intergenerational transmission of diabetes has been found.
On May 18, the results were published online in the top international journal "Nature".
This achievement provides the latest scientific perspective for human understanding and prevention and control of adult chronic diseases such as diabetes.
For some chronic diseases, symptomatic treatment is commonly used in the past.
Such as the treatment of diabetes, usually through insulin to control the increase in blood sugar, alleviate various complications caused by diabetes.
How to prevent the occurrence of diabetes has always puzzled the scientific and medical circles. How to find the origin of the disease from the early stage of life and carry out early intervention has become a global research hotspot.
As an obstetrician and gynecologist, Huang Hefeng often thinks about this question: what kind of influence will mothers have on offspring?
To this end, she led a team to carry out research on offspring adult diseases caused by adverse maternal environmental factors.
Combining clinical epidemiological investigations and research results of animal models, Huang Hefeng believes that adult chronic diseases such as diabetes and hypertension have developmental origins, so he took the lead in putting forward the theory of "gametogenic adult diseases" internationally.
However, this theory has not been effectively proved.
In order to confirm this hypothesis, Huang Hefeng's team began to focus on the following scientific questions: Does the adverse maternal environment before pregnancy affect the health of the offspring?
Taking the high incidence of diabetes in women of childbearing age as an example, does maternal hyperglycemia increase the risk of chronic disease in offspring through oocytes?
To this end, the research team established a female mouse model of diabetes.
To rule out the persistent effects of hyperglycemia on embryonic and fetal development, the researchers removed the affected oocytes for in vitro fertilization and embryo transfer, which were bred and nursed by healthy female mice.
At the same time, they performed metabolic tests on the offspring, and the results showed that the offspring mice showed impaired glucose tolerance.
These results suggest that oocytes are affected by an adverse environment of hyperglycemia, increasing the susceptibility of offspring to adult chronic diseases.
In response to this discovery, the research team began to think: What is the "culprit" that increases the susceptibility of offspring to diabetes?
After carrying out a series of complex experiments, the Zhejiang University team found a key key - the DNA demethylase TET3.
To this end, the Zhejiang University team has carried out in-depth cooperation with Xu Guoliang's research group.
The two teams collaborated to demonstrate that the high glucose environment in diabetic female mice resulted in insufficient doses of TET3 protein, which has the function of reprogramming DNA methylation profiles, in oocytes, which in turn allowed TET3 to enter the male pronucleus after fertilization to promote reprogramming. Insufficient potential, resulting in "under-demethylation" or "hypermethylation".
This is like the original ten farmers cultivating land, but now there are fewer people, and many fields are not fully cultivated, which affects future harvests, that is, the health of offspring is affected.
So what mechanism does TET3 use to increase the susceptibility of offspring to diabetes?
Studies have shown that hypermethylation and low expression of genes such as Gck in offspring islets lead to insufficient insulin secretion and decreased blood sugar lowering ability, which increases the susceptibility to diabetes with age.
It is reported that this research has also been confirmed clinically.
Huang Hefeng said that the innovation of the research results is that, taking pre-pregnancy diabetes as an entry point, the phenomenon that the environment acts on oocytes to induce adult diseases in offspring has been verified, and it is found that oocyte TET3 deficiency mediates the chronicity of offspring. The specific regulatory mechanism of disease occurrence.
"This result provides a transformative idea for the prevention and control of chronic diseases at the source, and provides a new perspective and strategy for improving the health of China's population." Huang Hefeng said.
It is reported that the units participating in this research include Zhejiang University, Fudan University, Chinese Academy of Sciences, Shanghai Jiaotong University, University of Chinese Academy of Sciences and the University of Ulster in the United Kingdom. Zhejiang University is the first unit of the paper.
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