Biol Trace Elem Res. 2025 Dec 18. doi: 10.1007/s12011-025-04949-8. Online ahead of print.
ABSTRACT
Unexplained recurrent spontaneous abortion (URSA) is a prevalent reproductive issue but its etiology remains obscure. Male exposure to environmental chemicals is suggested to elevate URSA risk in female partners. Herein, a case-control design set out to investigate associations between metal levels in human seminal plasma with URSA risk, plus to determine evidence of mediating effects by oxidative stress. Levels of 15 metal elements and oxidative stress marker malondialdehyde (MDA) in seminal plasma were measured in 125 male spouses of URSA cases compared to 108 male partners of women with successful pregnancy outcomes. The associations of single or mixed metals on URSA risk were analyzed using logistic regression and Bayesian kernel machine regression (BKMR), respectively. BKMR analyses reveal a joint effect of metal co-exposures on URSA risk. Through multiple statistical approaches, titanium (Ti), cadmium (Cd) or magnesium (Mg) were major contributors to metal mixtures elevating URSA risk. MDA was significantly and positively associated with URSA risk. Mediation analysis shows that the associations of Ti, Cd or Mg with URSA risk appear to be mediated by MDA at rates of 23.30%, 16.26% or 34.48%, respectively. In vitro experiments confirmed the seminal plasma relevant dose Ti, Cd or Mg exposure induced male mouse spermatocyte-derived GC-2 cells oxidative stress. Metal mixtures in seminal plasma are associated with increased URSA risk in female spouses, with Ti, Cd or Mg being significant contributors, potentially via oxidative stress, providing further insights into URSA etiology.
PMID:41410821 | DOI:10.1007/s12011-025-04949-8
