Men exposed to industrial air pollution have sperm mitochondrial DNA deletions

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In eukaryotic cells, mitochondria produce energy that is used for all cell functions. Two metabolic pathways that affect energy production are oxidative phosphorylation and glycolysis.

All cells are made up of different numbers of mitochondria, ranging from several hundred to thousands per cell. Each mitochondrion contains multiple copies of mitochondrial DNA (mtDNA).

To learn: Spectrum of sperm mtDNA deletions in males exposed to industrial air pollution. Photo Credit: Crevis/Shutterstock.com

background

Human mitochondrial circular DNA contains 37 genes encoding thirteen proteins, two ribosomal ribonucleic acids (rRNAs) and 32 transfer RNAs (tRNAs). Alterations in mtDNA sequences can affect mitochondrial functions that subsequently cause various complex neuromuscular, cardiovascular, gastrointestinal, and neurodegenerative diseases. Alterations in mtDNA can also lead to skin diseases, diabetes, cancer and aging.

Gene deletions can alter mtDNA sequences and have therefore been linked to mitochondrial dysfunction. The MitoBreak database includes approximately 1,300 deletions affecting 3-16,055 base pairs (bp) of the mitochondrial genome.

The majority of these deletions are found in the main arc of mtDNA. In particular, mtDNA abnormalities can cause heteroplasmy.

In sperm, there are mitochondria that surround the midsection of the sperm tail. Within sperm, mitochondria play important roles in sperm motility, capacitation, hyperactivation, and acrosome response.

Alterations in sperm mtDNA and the mitochondrial membrane have been linked to male infertility. Many common large mtDNA deletions have been reported in men with poor sperm motility. Interestingly, sperm mtDNA status can be used as a molecular biomarker for environmental exposure and oxidative stress.

In the Czech Republic, the Ostrava industrial agglomeration is a heavily polluted area with a high concentration of industry, local heating, coking plants and transport systems. In winter, there is a cross-border transfer of pollutants from neighboring industrial regions of Poland.

Air pollution in this area shows seasonal changes with increased circulation of particulate matter and gaseous pollutants, especially benzene and nitrous oxide. Compared to the summer months, air pollution increases in winter.

Previously, the researchers analyzed seed samples obtained from police officers in the city of Ostrava both in spring and in winter. To this end, an increased mtDNA deletion rate was observed in sperm samples collected in spring and then in winter.

In a recent Mutation research/genotoxicology and environmental mutagenesis Journal study, the same group of researchers compared the length spectra of sperm mtDNA deletions in two seasons with different air pollution levels.

About the study

The current study is part of the ongoing Healthy Aging in Industrial Environment (HAIE) project, which mainly focuses on the quality of life in the polluted region of the city of Ostrava.

A total of 54 healthy and non-smoking city police officers who patrolled the city of Ostrava on foot throughout the year were included in this study. All study participants reported moderate alcohol consumption, no substance abuse, and no exposure to additional chemical pollutants.

The general and reproductive health data of the participants were collected. No drastic lifestyle or dietary changes were observed during the study period, which helped rule out these confounding factors that may have impacted mtDNA. In addition, blood samples were taken for methylation and gene expression analysis.

study results

Higher sperm mtDNA deletion rates and sperm chromatin fragmentation were observed after the high exposure period in winter compared to summer season. Sperm analysis revealed increased levels of reactive oxygen species (ROS) and oxidative stress, which compromise sperm chromatin integrity and condensation upon maturation. These also impair sperm mobility and viability and impair mtDNA.

Reverse transcription polymerase chain reaction (RT-PCR) analysis showed increased sperm mtDNA deletion rates in samples collected in winter. However, this method could not compare the length spectra of the mtDNA deletions in the two seasons.

PCR primers were used to measure the length range of sperm mtDNA deletions in samples from two seasons. These primers enabled scanning of 8,066 bp of the most frequently deleted region of the mtDNA main arc.

A wide range of PCR product lengths was observed in the majority of sperm samples. In all sperm samples, the identified deleted sperm mtDNA molecules were significantly lower compared to undeleted sperm mtDNA. Most of the aberrant bands detected corresponded to PCR products of large deletions covering several kilobases (kb).

Conclusions

The study results are consistent with previous research showing that deleted mtDNA (mutant mtDNA) and normal mtDNA coexist in heteroplasmic cells. The sperm mtDNA deletions typically occur in spermatogonia and primordial cells. Genomic deletions also occur during sperm maturation.

Taken together, the current study found that air pollution did not induce large and small mtDNA deletions detectable by PCR and gel electrophoresis, respectively, in maturing sperm mtDNA.

Magazine reference:

  • Vozdova, M., Kubickova, S., & Rubes, J. (2022) Spectrum of sperm mtDNA deletions in men exposed to industrial air pollution. Mutation research/genotoxicology and environmental mutagenesis 882. doi:10.1016/j.mrgentox.2022.503538.
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