Endocrine-disrupting chemicals (EDCs) are ubiquitous, and exposure to them has been associated with adverse reproductive health in both animals and humans. While the adverse effects of maternal EDC exposures on pregnancy outcomes have been extensively investigated, an increasing body of literature is now examining the role of paternal exposure, given its potential impact on sperm epigenetics. This review summarizes human studies examining associations between paternal exposure to several EDCs and couples’ pregnancy outcomes. Biomarker-based studies suggest potential negative associations between paternal preconception exposure to certain phthalates and couples’ pregnancy outcomes, whereas studies for bisphenol A and parabens have shown little to no associations. The evidence regarding benzophenones, per- and polyfluoroalkyl substances, and flame-retardant chemicals remains limited and inconclusive. Given the critical knowledge gaps in this field, additional couple-based studies with repeated preconception exposure measurements are needed to clarify the effects of paternal exposure to individual EDCs and their mixtures on couples’ pregnancy outcomes. Additional studies on potential biological mechanisms that may explain these associations (e.g., sperm epigenome) are also warranted.
Han Han, R. Hauser, L. Mínguez-Alarcón· Current Environmental Health...· 0 citations
BACKGROUND
Sperm mitochondrial DNA copy number is an emerging marker of male fertility, with elevated mtDNAcn associated with poor semen quality across various populations. Sperm DNA methylation has also been previously demonstrated to be negatively correlated with semen parameters in IVF cohorts.
OBJECTIVE
To determine whether mtDNAcn is associated with nuclear DNA methylation across three population-based and clinical fertility cohorts.
DESIGN
The association between sperm mtDNAcn and genome-wide DNA methylation was investigated in 748 men from a general population cohort (LIFE; n = 379) and two infertility cohorts (SEEDS; n = 170 and EARTH; n = 199). Sperm DNA methylation and mtDNAcn were quantified by the Illumina EPIC (v1) array and triplex probe-based digital PCR, respectively. Covariate-adjusted linear regressions were conducted within each cohort and then meta-analyzed using METAL. Gene ontology analyses explored the biological relevance of differentially methylated CpGs (DMCs) and regions (DMRs).
RESULTS
Using a Holm-Bonferroni significance threshold, our analyses identified 1351, 224, and 258 DMCs and 2582, 1536, and 1284 DMRs in LIFE, SEEDS, and EARTH, respectively, indicating that higher sperm mtDNAcn was associated with DNA hypermethylation. In meta-analysis, 576 DMCs were associated with mtDNAcn. Notably, the genes corresponding with DMCs and DMRs are known critical regulators of male fertility and were enriched in the regulation of male meiosis, germline protection, spermatogenesis pathways, and early embryonic development.
DISCUSSION AND CONCLUSION
Our results, observed across three independent cohorts and supported by meta-analysis, indicate a consistent association between the sperm mitochondrial genome and nuclear DNA methylation, suggesting that mtDNAcn and methylation patterns may be linked during spermatogenesis. Further research is warranted to elucidate the mechanisms underlying these associations and to evaluate their relevance for reproductive outcomes.
S. Sawant, K. Nowak, Amanda L. Paskavitz et al.· Andrology· 0 citations
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