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

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Kristian Almstrup, Marie Lindhardt Johansen, Alexander S. Busch, Casper P Hagen, John E Nielsen, Jørgen Holm Petersen, Anders Juul

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 polymorphismsonly 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.
Original languageEnglish
Article number28657
JournalScientific Reports
Volume6
Pages (from-to)1-12
Number of pages12
ISSN2045-2322
DOIs
Publication statusPublished - 28 Jun 2016

Bibliographical note

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

This Article contains typographical errors in Table 1. In the column ‘Pubertal age’ the values for Boys-pre ‘1st–3rd Qu’ and ‘Range’ “−3.07–1.80” and “−5.06–0.42” should read: “of “−3.07– −1.80” and “−5.06– −0.42” respectively. In addition, the Girls-pre values for ‘1st–3rd Qu’ and ‘Range’ “−2.54–0.85” and “−6.01–0.42” should read: “−2.54– −0.85” and “−6.01– −0.42” respectively.

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