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

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.