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Exogenous Metals Indirectly Affect Human Semen Quality via Immune Cells at Single-Cell Resolution.

Nian Liu1, Guangming Li2, Guohuan Zhang3

  • 1School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.

Environment & Health (Washington, D.C.)
|September 25, 2025
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Summary

Environmental metal exposure negatively impacts male fertility by altering immune cells in semen. These immune cell changes, in turn, affect sperm quality, highlighting a crucial link between metals, immunity, and reproductive health.

Keywords:
exogenous metalsimmune cellindirect effectssemen qualitysingle-cell

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Area of Science:

  • Environmental health
  • Reproductive immunology
  • Toxicology

Background:

  • Immune modulation plays a vital role in male reproductive health and fertility.
  • Metals and metalloids are known for their immunomodulatory effects, but their impact on semen quality via immune pathways remains unclear.

Purpose of the Study:

  • To investigate the associations between exogenous metals within immune cells, immune cell proportions, and semen quality in healthy men.
  • To elucidate the indirect effects of metal exposure on male reproductive health through immune cell modulation.

Main Methods:

  • Utilized mass cytometry (CyTOF) for single-cell resolution analysis of immune cells in semen.
  • Measured exogenous metal concentrations within identified immune cells from 266 semen samples from 84 healthy men.
  • Performed mediation analyses to quantify indirect effects of metals on sperm parameters via immune cells.

Main Results:

  • Most detected metals in immune cells were inversely associated with immune cell proportions (p < 0.05), suggesting adverse effects.
  • Nonlinear, N-shaped associations were observed between immune cell proportions and key semen quality parameters (sperm concentration, motility).
  • Mediation analyses revealed that immune cells mediate 15.11% to 54.29% of the indirect effects of exogenous metals on sperm quality.

Conclusions:

  • Exogenous metal exposure adversely affects immune cells within semen.
  • Immune cell alterations indirectly impact male semen quality, linking environmental metal exposure to reproductive health.
  • Findings provide insights into the complex interactions between environmental factors, immune cells, and male fertility.