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

Tiancheng Zhang,Huijuan Shi,Jun Qian,Jun Wu,Xin Wang,Jianhui Li,Jufen Zheng,Xiaorong Shen,Liang Chen,Maohua Miao,Zhikai Wang,Bin Wu,Yan Fei Ru,Xuemei Wang,Haiyan Dong,Yihua Gu

doi:10.1186/s13578-021-00665-7

Tiancheng Zhang, Huijuan Shi + Show 14 more

Open Access

https://doi.org/10.1186/s13578-021-00665-7

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Abstract

InstructionLead (Pb) exposure is a risk factor for male infertility, but the epigenetic changes in sperm DNAattributable to lead exposure is poorly defined.MethodsIn 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.ResultsThe 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.DiscussionOverall, 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.

Highlights

Research suggests that the effect of Pb exposure on the sperm quality, an important indicator of male fertility, is dose-dependent [1]
Our findings showed that a blood Pb level (BLL) of 5–10 μg/dL can still reduce the sperm motility in men of childbearing age, which is inconsistent with the results of a previous Mexican cohort study [23]
Unlike a recent study in Southwest China, which reported that low Pb exposure adversely effects the sperm movement and density, our research shows that low Pb exposure is related only to the sperm motility

Summary

Introduction

Research suggests that the effect of Pb exposure on the sperm quality, an important indicator of male fertility, is dose-dependent [1]. Studies have shown that the Pb exposure in men with an average BLL of < 10 μg/dL causes reduced sperm quality. Similar results were observed in another study involving 240 volunteers with a median BLL of 4.92 μg/dL (range: 1.13–14.91 μg/dL) [4]. The analytical results of investigations examining the biological effects of low Pb exposure may be inaccurate, especially at a lower concentration range, if individuals exposed with a high BLL are included. Previous studies have failed to exclude individuals with a high BLL [3, 4]. We explored the potential effects of low Pb exposure on the sperm quality. Men with a BLL < 10 μg/dL were included

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Conclusion