It is known that low birth weight infants due to malnutrition during pregnancy are more likely to develop various lifestyle-related diseases after growth.
From past findings, it has been speculated that the cause of the onset is exposure to high concentrations of cortisol.The stress hormone glucocorticoid cortisol increases in late pregnancy and is metabolically degraded in normal pregnant women, while this defense mechanism is disrupted in undernourished pregnant women, exposing the fetus to high levels of cortisol.However, since cortisol levels normalize after birth, it was unclear why lifestyle-related diseases develop after growth.

　In this study, the activation of hypertension genes caused by high-concentration cortisol exposure during the fetal period remains as a memory due to the epigenetic mechanism (changes in gene expression regulation mechanisms such as histone modification and DNA methylation), and hypertension develops after growth. Focus on the hypothesis of letting.The study was conducted using rats fed a low-protein diet during pregnancy and rats treated with a synthetic glucocorticoid.

　As a result, all rat pups were weighed at birth, but became obese after growth and developed salt-sensitive hypertension in which blood pressure increased by salt intake.These model rats had reduced DNA methylation and, as a result, increased expression of the angiotensin-type I receptor gene associated with blood pressure regulation.In other words, it was found that the disruption of the gene expression regulation mechanism in the brain due to exposure to stress hormones during the fetal period is the mechanism that causes post-growth salt-sensitive hypertension.

　This result suggests that the adverse environment during pregnancy can cause lifestyle-related diseases in children and that it is important to improve the environment during the perinatal period.

Paper information:[JCI-Insight] Aberrant DNA methylation of hypothalamic angiotensin receptor in prenatal programmed hypertension