Association between sperm mitochondrial DNA copy number and deletion rate and industrial air pollution dynamics.
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ABSTRACT:
SUBMITTER: Vozdova M
PROVIDER: S-EPMC9117192 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
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Association between sperm mitochondrial DNA copy number and deletion rate and industrial air pollution dynamics.
Vozdova Miluse M Kubickova Svatava S Kopecka Vera V Sipek Jaroslav J Rubes Jiri J
Scientific reports 20220518 1
The effects of air pollution on men's reproductive health can be monitored by evaluating semen quality and sperm DNA damage. We used real-time PCR to analyse the effects of air pollution on sperm mitochondrial DNA copy number (mtDNAcn) and deletion (mtDNAdel) rates in semen samples collected from 54 men in two seasons with different levels of industrial and traffic air pollution. MtDNAdel rates were significantly higher following the high exposure period and were positively correlated with mtDNA ...[more]
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Project description:BackgroundAmbient particulate matter (PM) has been associated with mitochondrial damage and dysfunction caused by excessive oxidative stress, but the associations between long-term PM exposure and leukocyte mitochondrial DNA copy number (mtDNAcn), a biomarker of mitochondrial dysfunction due to oxidative stress, are less studied.ObjectivesTo investigate the associations between short-, intermediate- and long-term exposure (1-, 3- and 12-months) to different size fractions of PM (PM2.5, PM2.5-10 and PM10) and leukocyte mtDNAcn in a cross-sectional study.MethodsThe associations between each of the PM exposure metrics with z scores of log-transformed mtDNAcn were examined using generalized linear regression models in 2758 female participants from the Nurses' Health Study (NHS). Monthly exposures to PM were estimated from spatio-temporal prediction models matched to each participants' address history. Potential effect modification by selected covariates was examined using multiplicative interaction terms and subgroup analyses.ResultsIn single-size fraction models, increases in all size fractions of PM were associated with decreases in mtDNAcn, although only models with longer averages of PM2.5 reached statistical significance. For example, an interquartile range (IQR) increase in 12-month average ambient PM2.5 (5.5 μg/m3) was associated with a 0.07 [95% confidence interval (95% CI): -0.13, -0.01; p-value = 0.02] decrease in mtDNAcn z score in both basic- and multivariable-adjusted models. Associations for PM2.5 were stronger after controlling for PM2.5-10 in two size-fraction models.ConclusionsOur study suggests that long-term exposure to ambient PM2.5 is associated with decreased mtDNAcn in healthy women.
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Project description:Study questionAre sperm mitochondrial DNA copy number (mtDNAcn) and deletion rate (mtDNAdel) associated with odds of fertilization and high embryo quality at Days 3 and 5?Summary answerHigher sperm mtDNAcn and mtDNAdel were associated with lower odds of high quality Day 3 embryos and transfer quality Day 5 embryos, both of which were primarily driven by lowered odds of fertilization.What is known alreadySperm mtDNAcn and mtDNAdel have been previously associated with poor semen parameters and clinical male infertility. One prior study has shown that mtDNAdel is associated with lower fertilization rates. However, it is unknown whether these characteristics are linked with ART outcomes.Study design, size, durationThis prospective observational study included 119 sperm samples collected from men undergoing ART in Western Massachusetts. ART outcomes were observed through to Day 5 post-insemination.Participants/materials, settings, methodsAs part of the Sperm Environmental Epigenetics and Development Study (SEEDS), 119 sperm samples were collected from men undergoing ART in Western Massachusetts. Sperm mtDNAcn and mtDNAdel were measured via triplex probe-based qPCR. Fertilization, Day 3 embryo quality and Day 5 embryo quality measures were fitted with mtDNAcn and mtDNAdel using generalized estimating equations.Main results and the role of chanceAfter adjusting for male age and measurement batches, higher sperm mtDNAcn and mtDNAdel were associated with lower odds of fertilization (P = 0.01 and P < 0.01), high quality Day 3 embryos (P = 0.02 for both) and transfer quality Day 5 embryos (P = 0.01 and P = 0.09). However, the associations of mtDNAcn and mtDNAdel with Day 3 high quality status and Day 5 transfer quality status were attenuated in models restricted to fertilized oocytes. Sperm mtDNAcn and mtDNAdel remained statistically significant in models adjusted for both male age and semen parameters, although models including both mtDNA markers generally favoured mtDNAdel.Limitations, reasons for cautionOur sample only included oocytes and embryos from 119 couples and thus large diverse cohorts are necessary to confirm the association of sperm mtDNA biomarkers with embryo development.Wider implications of the findingsTo our knowledge, our study is the first to assess the associations of sperm mtDNAcn and mtDNAdel with fertilization and embryo quality. The biological mechanism(s) underlying these associations are unknown. Multivariable models suggest that sperm mtDNAcn and mtDNAdel provide discrimination independent of age and semen parameters; therefore, future investigation of the utility of sperm mtDNA as a biomarker for ART outcomes is warranted.Study funding/competing interest(s)This work was supported by Grant (K22-ES023085) from the National Institute of Environmental Health Sciences. The authors declare no competing interests.Trial registration numberN/A.
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