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Abstract Research question To examine associations between sperm mitochondrial DNA copy number (mtDNAcn), sperm mitochondrial DNA deletions (mtDNAdel), semen parameters and clinical infertility in an IVF setting. Design A total of 125 sperm samples were collected from men undergoing assisted reproductive procedures in an IVF clinic in Western Massachusetts, USA. Sperm mtDNAcn and mtDNAdel were measured by probe-based quantitative polymerase chain reaction. Semen parameters, clinical diagnoses of infertility, and infertility based on consecutive semen parameters, were fitted with mtDNAcn and mtDNAdel in linear models. The utility of sperm mtDNAcn and mtDNAdel to predict infertility was assessed by receiver operating characteristic curves. Results Adjusting for relevant covariates, both sperm mtDNAcn and mtDNAdel were associated with lower sperm concentration, count, motility and morphology (P ≤ 0.03). Sperm mtDNAcn and mtDNAdel were also associated with increased risks of clinical infertility based on current and consecutive semen samples. Sperm mtDNAcn had high predictive accuracy for consecutive diagnoses of clinical infertility (C-statistic: 0.91), whereas sperm mtDNAdel had moderate predictive accuracy (C-statistic: 0.75). Conclusions Sperm mtDNAcn is a measure of consecutive abnormal semen parameters and has promise as a diagnostic test. [ABSTRACT FROM AUTHOR]

Background: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans., Objective: To investigate associations between PFAS concentrations and miRNA levels in children., Methods: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and 64 participants (average age 6.5 years, 39.1% female) from the Rhea study, a mother-child cohort in Greece. PFAS concentrations and miRNA levels were assessed in plasma samples from both studies. Associations between individual PFAS and plasma miRNA levels were examined after adjusting for covariates. Additionally, the cumulative effects of PFAS mixtures were evaluated using an exposure burden score. Ingenuity Pathways Analysis was employed to identify potential disease functions of PFAS-associated miRNAs., Results: Plasma PFAS concentrations were associated with alterations in 475 miRNAs in the Teen-LABs study and 5 miRNAs in the Rhea study (FDR p < 0.1). Specifically, plasma PFAS concentrations were consistently associated with decreased levels of miR-148b-3p and miR-29a-3p in both cohorts. Pathway analysis indicated that PFAS-related miRNAs were linked to numerous chronic disease pathways, including cardiovascular diseases, inflammatory conditions, and carcinogenesis., Conclusion: Through miRNA screenings in two independent cohorts, this study identified both known and novel miRNAs associated with PFAS exposure in children. Pathway analysis revealed the involvement of these miRNAs in several cancer and inflammation-related pathways. Further studies are warranted to enhance our understanding of the relationships between PFAS exposure and disease risks, with miRNA emerging as potential biomarkers and/or mediators in these complex pathways., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vaia Lida Chatzi reports financial support was provided by The National Institute of Environmental Health Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Population aging is a looming global health challenge. New biological aging metrics based on DNA methylation levels have been developed in addition to traditional aging biomarkers. The prospective relationships of aging biomarkers with mitochondrial changes are still not well understood. Here, we examined the prospective associations of mitochondrial copy number (mtDNAcn) with several aging biomarkers - DNAm-Age, DNAm-PhenoAge, DNAm-GrimAge, and leukocyte telomere length. We analyzed 812 individuals from Veteran Affairs Normative Aging Study (NAS) with available blood samples from 1999-2013. Whole blood mtDNAcn and relative leukocyte telomere length were measured via qPCR. DNA methylation was assessed and used to calculate DNAm-Age, DNAm-GrimAge, and DNAm-PhenoAge. Linear mixed models were used to quantify the associations of mtDNAcn with DNAm-Age, DNAm-GrimAge, DNAm-PhenoAge, and leukocyte telomere length. In multivariable cross-sectional analyses, mtDNAcn is negatively associated with DNAm-Age PhenoAge and DNAm-PhenoAge. In contrast, mtDNAcn is associated with prospective measures of higher DNAm-PhenoAge and shorter leukocyte telomere length. Our study shows that higher mtDNAcn is associated with prospective measures of greater DNAm-PhenoAge and shorter leukocyte telomere length independent of chronological age. This indicates a role for mitochondrial in aging-related disease and mortality, but not the departure of biological age from chronological age.