Will it be inherited across generations? Professor Zeng Chunyu’s team from the Department of Cardiology at the Army Specialty Medical Center (Daping Hospital) of the Army Medical University found the answer after 6 years of research.
Professor Zeng Chunyu’s team published research results online on August 25 in the top international cardiovascular disease research journal "Circulation" (impact factor 39.9): maternal infection during pregnancy can lead to high blood pressure and abnormal urinary sodium metabolism in offspring, and will Transgenerational inheritance occurs through the maternal line, that is, the first three generations show spontaneous hypertension, and the fourth and fifth generations show salt-sensitive hypertension , and the potential molecular mechanism of its transgenerational inheritance is elucidated.
(Picture: LPS exposure during pregnancy leads to the mechanism model of transgenerational inherited hypertension)
Zeng Chunyu's team established a pregnancy infection model by intraperitoneally injecting lipopolysaccharide (Gram-negative bacterial endotoxin) into pregnant rats, and the resulting offspring Rats develop hypertension and urinary sodium metabolism disorders. If the offspring of hypertensive female rats are bred with normotensive male rats, their offspring will also develop spontaneous hypertension until the third generation. Further observation revealed that the fourth-generation rats obtained by breeding third-generation hypertensive female rats with normotensive male rats did not develop spontaneous hypertension, but did develop hypertension when induced by a high-salt diet (high salt sensitivity). blood pressure), this phenomenon gradually disappeared in the sixth generation.
(Illustration: Team of Professor Zeng Chunyu, Department of Cardiology, Army Specialty Medical Center, Army Medical University)
It is worth noting that although high blood pressure caused by infection during pregnancy can be inherited, it does not affect gene (DNA) variation. Infection during pregnancy can cause intrauterine oxidative stress and inflammation. In the egg cells of unborn female rats in utero, the expression of histone demethylase KDM3B will be abnormally increased, and the histone H3K9me2 alpha in the kidneys of their offspring will be abnormal. The level of basal modification is reduced, which increases the expression of RAC1 gene, leading to abnormal activation of mineralocorticoid receptor (MR) signaling, and ultimately leads to natriuresis disorder and hypertension. The H3K9me2 methylation level in subsequent generations of kidneys continues to decrease, the RAC1-MR pathway is activated, and the main mechanism of transgenerational inheritance is formed. It can be understood this way: The change in the level of H3K9me2 methylation is like a "carving knife" causing deep "notches" in the gene expression process. After several generations, the "notches" always exist, and histone demethylation The chemical enzyme KDM3B is the "carving knife", and intrauterine oxidative stress is the "hand" holding the carving knife, which is the driving force behind epigenetic changes.
In response to this "epigenetic" mechanism, Professor Zeng Chunyu's team further looked for treatment measures from the root cause, using the antioxidant tempol to intervene in rats infected during pregnancy, which effectively prevented hypertension and urinary sodium metabolism in subsequent generations. abnormal. Professor Zeng Chunyu said that this study provides a new theoretical basis and prevention and treatment measures for hypertension, the primary risk factor for cardiovascular disease. At the same time, with the opening of the country's "three-child policy", people should pay more attention to avoiding adverse stimulation during pregnancy on their children. potential health effects.
Source: Xinhua News Agency
