Effects of low lead exposure on sperm quality and sperm DNA methylation in adult men

Abstract

Instruction Lead (Pb) exposure is a risk factor for male infertility, but the epigenetic changes in sperm DNAattributable to lead exposure is poorly defined. Methods In this study, we investigated whether low Pb exposure (< 10 µg/dL) affects the sperm quality. Blood, urine, and semen samples of 297 men of childbearing age were analyzed for all relevant parameters. Based on the blood Pb level (BLL), participants were allocated to RL (0–2.5 µg/dL), RM (2.5–5 µg/dL), and RH (5–10 µg/dL) groups. The 5-methylcytosine and 5-hydroxymethylcytosine patterns in the sperm DNA were identified using methylated DNA immunoprecipitation and hydroxymethylated DNA immunoprecipitation sequencing. Results The non-progressive motility (NP) was significantly increased and associated with global hypomethylation of sperm DNA in the RH group compared with the RL group, indicating that aberrant sperm methylation due to low Pb exposure is possibly associated with reduced sperm motility. The hypomethylated promoter regions were primarily enriched in the calcium (Ca) homeostasis pathway. Further, the interaction between Ca and Pb was associated with sperm rapid progressive motility and asthenospermia risk, although no significant methylation abnormality was observed in those with BLL < 5 µg/dL. When BLL was > 5 µg/dL or when predicting NP, no significant Pb–Ca interaction was observed. Discussion Overall, our results indicate that aberrant DNA methylation of the Ca homeostasis pathway, induced by low Pb exposure, is the potential cause for reduced sperm velocity.

Developmental exposures to common environmental contaminants, DEHP and lead, alter adult brain and blood hydroxymethylation in mice

“…Pb-exposed females showed no differences in hydroxymethylation; only Pb-exposed male brains had increases in hydroxymethylation in the brain. Hydroxymethylation differences after Pb exposure have been explored in various Frontiers in Cell and Developmental Biology frontiersin.org human tissues, including childhood blood (Rygiel et al, 2021), cord blood (Sen et al, 2015;Okamoto et al, 2022), toenail and placenta (Tung et al, 2022), and sperm (Zhang et al, 2021). Epigenome-wide differences were only assessed in toenails/placenta using the EPIC array (Tung et al, 2022) and in sperm using hMeDip-seq (Zhang et al, 2021).…”

“…Hydroxymethylation differences after Pb exposure have been explored in various Frontiers in Cell and Developmental Biology frontiersin.org human tissues, including childhood blood (Rygiel et al, 2021), cord blood (Sen et al, 2015;Okamoto et al, 2022), toenail and placenta (Tung et al, 2022), and sperm (Zhang et al, 2021). Epigenome-wide differences were only assessed in toenails/placenta using the EPIC array (Tung et al, 2022) and in sperm using hMeDip-seq (Zhang et al, 2021). In toenails and placentas, most of the differentially hydroxymethylated sites were higher with Pb exposure (Tung et al, 2022), whereas sperm showed mostly lower hydroxymethylated regions (Zhang et al, 2021).…”

“…Epigenome-wide differences were only assessed in toenails/placenta using the EPIC array ( Tung et al, 2022 ) and in sperm using hMeDip-seq ( Zhang et al, 2021 ). In toenails and placentas, most of the differentially hydroxymethylated sites were higher with Pb exposure ( Tung et al, 2022 ), whereas sperm showed mostly lower hydroxymethylated regions ( Zhang et al, 2021 ). Presently, all male cortex regions had higher hydroxymethylation with Pb exposure.…”

Poor semen parameters are associated with abnormal methylation of imprinted genes in sperm DNA

“…Although many genetic and environmental factors have been confirmed to affect semen quality parameters, the vast majority of male infertility is still unknown [30][31][32]. The DNA methylation status of sperms has emerged as a novel biomarker that can provide information related to male fertility [27,33,34].…”

An Overview of E-Cigarette Impact on Reproductive Health

“…As a consequence of the heating process of e-fluid and the device components, e-cigarettes release numerous metal nanoparticles such as lead, nickel, chromium, aluminum, iron, copper, silver, zinc, tin, manganese, ceramic, and silica [ 10 , 61 ]. Although the impact of male exposure to these metals in the context of e-cigarette utilisation has not yet been proven, environmental exposure to these nanoparticles was shown to negatively affect human sperm concentration, sperm motility, and sperm function with a potential effect on fertility status [ 65 , 66 , 67 , 68 , 69 , 70 ]. At high concentrations, cadmium was reported to have detrimental effects on human, bovine, and murine oocyte maturation, fertilization, early cleavage, and blastocyst development rates [ 62 , 71 ].…”