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Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood

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@article{a65adbd79a3d43b5a49ac69c6664f788,
title = "Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood",
abstract = "Puberty marks numerous physiological processes which are initiated by central activation of the hypothalamic-pituitary-gonadal axis, followed by development of secondary sexual characteristics. To a large extent, pubertal timing is heritable, but current knowledge of genetic polymorphisms only explains few months in the large inter-individual variation in the timing of puberty. We have analysed longitudinal genome-wide changes in DNA methylation in peripheral blood samples (n = 102) obtained from 51 healthy children before and after pubertal onset. We show that changes in single methylation sites are tightly associated with physiological pubertal transition and altered reproductive hormone levels. These methylation sites cluster in and around genes enriched for biological functions related to pubertal development. Importantly, we identified that methylation of the genomic region containing the promoter of TRIP6 was co-ordinately regulated as a function of pubertal development. In accordance, immunohistochemistry identified TRIP6 in adult, but not pre-pubertal, testicular Leydig cells and circulating TRIP6 levels doubled during puberty. Using elastic net prediction models, methylation patterns predicted pubertal development more accurately than chronological age. We demonstrate for the first time that pubertal attainment of secondary sexual characteristics is mirrored by changes in DNA methylation patterns in peripheral blood. Thus, modulations of the epigenome seem involved in regulation of the individual pubertal timing.",
keywords = "Journal Article",
author = "Kristian Almstrup and {Lindhardt Johansen}, Marie and Busch, {Alexander S} and Hagen, {Casper P} and Nielsen, {John E} and Petersen, {J{\o}rgen Holm} and Anders Juul",
year = "2016",
month = "6",
day = "28",
doi = "10.1038/srep28657",
language = "English",
volume = "6",
pages = "28657",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Pubertal development in healthy children is mirrored by DNA methylation patterns in peripheral blood

AU - Almstrup, Kristian

AU - Lindhardt Johansen, Marie

AU - Busch, Alexander S

AU - Hagen, Casper P

AU - Nielsen, John E

AU - Petersen, Jørgen Holm

AU - Juul, Anders

PY - 2016/6/28

Y1 - 2016/6/28

N2 - Puberty marks numerous physiological processes which are initiated by central activation of the hypothalamic-pituitary-gonadal axis, followed by development of secondary sexual characteristics. To a large extent, pubertal timing is heritable, but current knowledge of genetic polymorphisms only explains few months in the large inter-individual variation in the timing of puberty. We have analysed longitudinal genome-wide changes in DNA methylation in peripheral blood samples (n = 102) obtained from 51 healthy children before and after pubertal onset. We show that changes in single methylation sites are tightly associated with physiological pubertal transition and altered reproductive hormone levels. These methylation sites cluster in and around genes enriched for biological functions related to pubertal development. Importantly, we identified that methylation of the genomic region containing the promoter of TRIP6 was co-ordinately regulated as a function of pubertal development. In accordance, immunohistochemistry identified TRIP6 in adult, but not pre-pubertal, testicular Leydig cells and circulating TRIP6 levels doubled during puberty. Using elastic net prediction models, methylation patterns predicted pubertal development more accurately than chronological age. We demonstrate for the first time that pubertal attainment of secondary sexual characteristics is mirrored by changes in DNA methylation patterns in peripheral blood. Thus, modulations of the epigenome seem involved in regulation of the individual pubertal timing.

AB - Puberty marks numerous physiological processes which are initiated by central activation of the hypothalamic-pituitary-gonadal axis, followed by development of secondary sexual characteristics. To a large extent, pubertal timing is heritable, but current knowledge of genetic polymorphisms only explains few months in the large inter-individual variation in the timing of puberty. We have analysed longitudinal genome-wide changes in DNA methylation in peripheral blood samples (n = 102) obtained from 51 healthy children before and after pubertal onset. We show that changes in single methylation sites are tightly associated with physiological pubertal transition and altered reproductive hormone levels. These methylation sites cluster in and around genes enriched for biological functions related to pubertal development. Importantly, we identified that methylation of the genomic region containing the promoter of TRIP6 was co-ordinately regulated as a function of pubertal development. In accordance, immunohistochemistry identified TRIP6 in adult, but not pre-pubertal, testicular Leydig cells and circulating TRIP6 levels doubled during puberty. Using elastic net prediction models, methylation patterns predicted pubertal development more accurately than chronological age. We demonstrate for the first time that pubertal attainment of secondary sexual characteristics is mirrored by changes in DNA methylation patterns in peripheral blood. Thus, modulations of the epigenome seem involved in regulation of the individual pubertal timing.

KW - Journal Article

U2 - 10.1038/srep28657

DO - 10.1038/srep28657

M3 - Journal article

VL - 6

SP - 28657

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

ER -

ID: 49277387