Masato Kantake
Juntendo University Shizuoka Hospital, Japan
Title: Postnatal relative adrenal insufficiency results in methylation of the glucocorticoid receptor gene in preterm infants
Biography
Biography: Masato Kantake
Abstract
Early life experiences impact on the neurobiological regulation of stress responsiveness, mood, and anxiety disorders. Maternal care, familial functioning, and childhood adversity all contribute to neurobiological regulation through epigenetic modification of DNA, which is thought to be highly stable across a lifespan. Hippocampal glucocorticoid receptor (GR) plays a central role in modulating hypothalamus pituitary adrenal axis activity. We have investigated the relationship between early life stress in NICU such as invasive treatment and the methylation rates in GR gene promoter 1F region which is known to be important for developing neurodevelopmental disabilities in later life. Cell-free DNA was extracted from preterm birth infants at birth and at one and two months after birth. Through bisulfite amplicon sequencing using an Illumina Miseq system and Bismarck-0.15.0 software, we identified the rate of cytosine methylation. Postnatal glucocorticoid administration to treat circulatory collapse was the most-associated independent variable with a positive regression coefficient for a change in methylation rate at nine of the 39 analyzed CpG sites. It also influenced the methylation ratio at 22 of the 39 CpG sites at two months of age. The standard deviation score of body weight at birth was extracted as an independent variable, with a negative regression coefficient at nine of the 22 CpG sites together with glucocorticoid administration. The results of this study indicate that a prenatal environment that results in intrauterine growth restriction and postnatal relative adrenal insufficiency requiring glucocorticoid administration leads to GR gene methylation. That, in turn, may result in neurodevelopmental disabilities.