Association of blood leukocyte DNA methylation at LINE-1 and growth-related candidate genes with pubertal onset and progression

Abstract

Puberty is a developmentally plastic phase. Variations in pubertal tempo have implications for the risk of later adult diseases. Influences on pubertal tempo have been widely discussed, but the underlying biological mechanisms remain unclear. Epigenetic modifications are known to regulate development processes; they could play an important role in affecting pubertal outcomes. We conducted a population-based analysis to investigate the association of peripubertal blood DNA methylation at LINE-1 and growth-related candidate genes with pubertal onset and progression in healthy adolescents. The analytic sample included 114 males and 129 females aged 10 to 18 years. DNA methylation at growth-related candidate loci IGF2, H19, HSD11B2, as well as LINE-1 repetitive elements were quantified. Cox survival and ordinal regression models were used to examine sexand locus-specific associations of epigenetic markers with pubertal development using physicianassessed Tanner stages and self-reported menarche, adjusted for covariates. Among boys, DNA methylation at H19 was associated with later pubarche. HSD11B2 methylation was associated with earlier onset of pubic hair and genitalia development and slower pubertal progression. IGF2 was associated with later onset of genital development. Among girls, LINE-1 methylation was associated with later onset of breast development. For each percent increase of methylation at H19, there was 5% increased odds in the earlier onset of breast development. DNA methylation of IGF2 was associated with earlier onset of pubic hair. DNA methylation at genes known to influence early-life growth may also influence pubertal outcomes.

In utero and peripubertal metals exposure in relation to reproductive hormones and sexual maturation and progression among boys in Mexico City

“…In this study, we observed slower progression of sexual maturation for those boys at higher Tanner stages at the early-teen visit which was also reported in studies explored the association between pubertal onset and progression [115][116][117]. A compensatory mechanism similar to "catch-up growth" was proposed previously as a potential explanation for this observation [68,70]. For those boys who had experienced a delayed pubertal development, their body systems may have responded by accelerating the tempo of pubertal progression (the change from lower stages of puberty to higher stages); while others who had experienced an advanced pubertal development may respond by slowing down the pubertal progression.…”

“…Participants in this study are part of the "Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT)" project, a longitudinal cohort study of pregnant women in Mexico City and their children [67]. ELEMENT recruited 997 pregnant women from maternity hospitals during their first trimester between 1997 and 2004 and their children, as previously described [21,[67][68][69][70]. Inclusion criteria included not planning to leave the area within 5 years; no history of infertility, diabetes, or psychosis; not consuming alcoholic beverages daily during pregnancy; no addiction to illegal drugs; no diagnosis of a high-risk pregnancy; being pregnant with singleton.…”

In Utero and Peripubertal Metals Exposure in Relation to Reproductive Hormones and Sexual Maturation and Progression among Boys in Mexico City

“…In this study, we observed slower progression of sexual maturation for those boys at higher Tanner stages at the early-teen visit which was also reported in studies explored the association between pubertal onset and progression [118][119][120]. A compensatory mechanism similar to "catch-up growth" was proposed previously as a potential explanation for this observation [71,73]. For those boys who had experienced a delayed pubertal development, their body systems may have responded by accelerating the tempo of pubertal progression (the change from lower stages of puberty to higher stages); while others who had experienced an advanced pubertal development may respond by slowing down the pubertal progression.…”

Sleep duration and fragmentation in relation to leukocyte DNA methylation in adolescents

“…We focused on four regions that have been studied by our group before and are associated with environmental exposures [17][18][19] and/or with pubertal markers [20]. The first was LINE-1 (long interspersed nuclear elements) repetitive elements, which serve as a marker of global levels of DNA methylation.…”