A major breakthrough has been made in the research of developmental diabetes, and the research results of the team of Academician Huang Hefeng/Academician Xu Guoliang are published in Nature

Comments: Antoine HFM Peters (Professor at the Friedrich-Miscotian Institute for Biomedical Research, Switzerland), Marisa Bartolomei (Academician of the National Academy of Sciences), Yan Wei (Director of the National Center for Reproductive Epigenetics), Guan Minxin ( Director of Institute of Genetics, Zhejiang University)

The DOHaD theory (Developmental Origins of Health and Disease) was first proposed by Professor Barker in the UK in the 198

Diabetes is one of the main chronic diseases affecting human health, with a high incidence and hidden ons.

Recently, the research team of Academician Huang Hefeng, Director of the Key Laboratory of Reproductive Genetics (Zhejiang University) of the Ministry of Education, Honorary Dean of the Obstetrics and Gynecology Hospital Affiliated to Zhejiang University School of Medicine, and Academician Xu Guoliang of the Center for Excellence and Innovation of Molecular and Cell Science, Chinese Academy of Sciences, have conducted research on gamete/embryo-derived The research on diseases has made important new discoveri.

Eggs: Mediating Transgenerational Inheritance of Diabetes

The research team of Academician Huang Hefeng discovered early that high sugar, high fat and other factors exposure during pregnancy or before the father's pregnancy can change DNA methylation and induce metabolic abnormalities in offspri.

Figure 1: Experimental design and main phenotypic results of offspring

Tet3: a key molecule in the inheritance of oocyte-derived diabetes

In order to find the key molecules that mediate the transgenerational effect of oocytes, the researchers took the epigenetic mechanism as a breakthrough, and further studied the DNA demethylase Tet3 (tet methylcytosine) in the oocytes of hyperglycemic mi.

Figure 2: High glucose leads to decreased Tet3 and 5hmc in oocytes/blastocysts and progeny islets, and hypermethylated Gck promoter region

Paternal genes: mediators of offspring transmission of metabolic imprinting from high-glucose eggs

In order to verify the source and inheritability of the changes in the methylation profile of the offspring, the research group took the target gene Gck as an example, and found that the hypermethylation of the Gck promoter originated from the male pronucleus of fertilized eggs, and continued to develop with developme.

Prospects: The same phenotype appears in the eggs of diabetic patients

More interestingly, GV-stage oocytes and blastocysts of diabetic patients also showed a trend of decreased Tet3 expression and hypermethylation of the Gck promoter region, respectively (Figure 3), suggesting the research team's findings in a mouse mod.

Figure 3: Diabetes (in vivo) and high glucose (in vitro) lead to decreased expression of Tet3 in human oocytes

To sum up, this study has achieved a major breakthrough in the study of developmental adult diseas.

The first author unit of this study and the first unit of the main corresponding author are the Key Laboratory of Reproductive Genetics of the Ministry of Education (Zhejiang Universit.

The research team led by Academician Huang Hefeng has been deeply engaged in the theoretical research of "gamete/embryo-derived diseases" for many yea.

Expert Reviews

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As one of the most common metabolic diseases in modern society, the incidence of diabetes remains high, and it has become the most harmful public health problem in the wor.

Based on the above-mentioned high attention and recognition of the research results, Pr.

Yan Wei and Pr.

Marisa Bartolomei, academician of the National Academy of Sciences, wrote a highlight comment on the NATURE article in the journal Biology of Reproduction: "This study establishes the relationship between pre-pregnancy hyperglycemia and oocyt.

The link between adverse epigenome effects and a higher risk of developing metabolic disturbances in offspring also sheds light on an underlying mechani.

This hypothesis has never been tested before, let alone the molecular mechanism of regulati.

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Guan Minxin (Director of Institute of Genetics, Zhejiang University, expert in the field of genetics)

Since the DOHaD theory was promoted in China, a number of research results have confirmed that the high-sugar environment in women during pregnancy can increase the risk of diabetes/obesity/cardiovascular disease in offspri.

Based on the theory of "gamete/embryo-derived disease", Academician Huang Hefeng put forward the scientific hypothesis that female oocytes can be used as a medium to mediate health risks related to offspring caused by high-glucose exposure before pregnan.

Academician Xu Guoliang, the academic leader in the field of epigenetics and developmental biology, has jointly tackled key problems, and the cooperation model with complementary advantages is worth learning from pee.

This is a landmark and original research, which is not only the extension and deepening of Academician Huang Hefeng's research in the field of "gamete/embryo-derived diseases", but also for the study of metabolic diseases caused by the environment or diet and the generation of other acquired trai.

Intra- and trans-generational inheritance opens up new research directio.

The study used in vitro fertilization to obtain embryos from oocytes exposed to a high-glucose environment, and further obtained offspring by transferring the embryos to surrogate female mi.

Ingeniously avoiding the interference factor of intrauterine high glucose exposure during pregnancy that cannot be ruled out in previous studies, and specifically studying the impact of pre-pregnancy hyperglycemia on offspring heal.

In addition, using epigenetics as an entry point, we traced the expression changes of the key regulatory factor TET3 and the resulting methylation degree of insulin secretion-related factor promoter regions in mouse oocytes, blastocysts and offspring isle.

to chan.

What is more noteworthy is that this study used extremely precious clinical samples and found a phenotype similar to that of the mouse model: GV-stage oocytes and blastocysts of diabetic patients also showed a trend of decreased Tet3 expression and hypermethylation of the Gck promoter region, respective.

stat.

This suggests that the research team's findings in the mouse model may be analogous to diabetic patients, and provides an important theoretical support for the feasibility of correcting epigenetic variations and the diseases they cause by intervening in the reprogramming of fertilized eg.

Prospects for clinical applicati.

Original link:

Maternal inheritance of glucose intolerance via oocyte TET3 insufficiency

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