DNA methylation of LINE-1 and Alu repetitive elements in relation to sex hormones and pubertal timing in Mexican-American children

Abstract

Background: The molecular mechanisms linking environmental exposures to earlier pubertal development are not well characterized. Epigenetics may play an important role, but data on the relationship between epigenetic marks and puberty, particularly in humans, is limited. Methods: We used pyrosequencing to measure Alu and long interspersed nucleotide elements (LINE-1) methylation in DNA isolated from whole blood samples collected from newborns and 9-y-old children (n = 266). Tanner staging was completed six times between ages 9 and 12 y to determine pubertal status, and hormone levels were measured in 12-y-old boys. Results: Among girls, we observed a suggestive trend of increased odds of breast and pubic hair development with higher Alu and LINE-1 methylation in 9-y-old blood, respectively. The strongest association identified was an inverse association of LINE-1 methylation in 9-y-old girls with odds of experiencing menarche by age 12 (OR (95% CI): 0.63 (0.46, 0.87); P = 0.005). We observed a consistent inverse relationship for Alu and LINE-1 methylation at 9 y with luteinizing hormone (LH), testosterone and follicle-stimulating hormone levels in boys but it was only significant between LINE-1 and LH. Conclusion: DNA methylation of Alu and LINE-1 may be involved in puberty initiation and development. This relationship should be confirmed in future studies.