Association of Bisphenol A Exposure with LINE-1 Hydroxymethylation in Human Semen

Abstract

Bisphenol A (BPA), an exogenous endocrine-disrupting chemical, has been shown to alter DNA methylation. However, little information is available about the effect of BPA exposure on DNA hydroxymethylation in humans. The objective of the present study was to examine whether BPA exposure was associated with DNA hydroxymethylation in human semen samples. We measured urine BPA levels and LINE-1 hydroxymethylation in 158 male factory workers selected from an occupational cohort study conducted in China between 2004 and 2008. Among them, there were 72 male workers with occupational BPA exposure (BPA-exposed group) and 86 male workers without occupational BPA exposure (unexposed group). Multivariate linear regression models were used to examine the association of exposure to BPA with LINE-1 hydroxymethylation. LINE-1 was more highly hydroxymethylated in the BPA-exposed group than in the unexposed group (median 12.97% vs. 9.68%, respectively; p < 0.05), after adjusting for the potential confounders. The medians of 5-hydroxymethylcytosine (5hmC) generally increased with increasing urine BPA levels: 8.79%, 12.16%, 11.53%, and 13.45%, for undetected BPA and corresponding tertiles for the detected BPA, respectively. After analysis using data at individual level, our findings indicated that BPA exposure was associated with alterations of sperm LINE-1 hydroxymethylation, which might have implications for understanding the mechanisms underlying BPA-induced adverse effects on male reproductive function.

Bisphenol A-Induced Epigenetic Changes and Its Effects on the Male Reproductive System

“…In particular, a genome-wide study on semen samples from workers exposed to BPA and unexposed controls showed the ability of that compound to interfere with gene expression during spermatogenesis, with DNA hydroxymethylation due to H3 trimethylation, clinically ending in reduced sperm concentration motility ( 41 ). More recent data confirm previous findings, especially demonstrating a LINE-1 hydroxymethylation ( 42 ). Since LINE-1 activation has already been studied in relation to male infertility, its epigenetic modifications induced by BPA exposure may be one of the mechanisms for this EDC's toxicity.…”

Multivariate models for estimating jackass semen production and quality

“…In previous studies, multivariate regression model was used to analyse the influencing factors of semen characteristics of boar (Wang et al., 2017) and humans (Ji et al., 2018; Tian et al., 2018), and to predict the fertility of motile sperm subpopulations in rabbit (Quintero‐Moreno et al., 2007) and dog (Pena et al., 2018), and semen cryopreservation outcomes in humans (Jiang et al., 2016). On the basis of the observed data, this approach could establish appropriate dependent relationships between variables, and was usually applied in forecasting and control issues (Jiang et al., 2016).…”

Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism

“…2015)—have demonstrated alterations in human sperm DNA methylation. All but one of these studies (Tian et al. 2018) used different versions of Illumina®’s methylation array or RRBS.…”