Exploring the impact of the common (4977 bp) and ATPase mitochondrial DNA deletion on the copy number and telomere length in a sample of infertile Iraqi men.

BACKGROUND: Genetic factors contribute to 15–30% of male infertility, with mitochondrial DNA (mtDNA) alterations, including the 4977 bp and ATPase gene deletions, being closely linked to reduced sperm motility and fertility. OBJECTIVE: To investigate the presence and frequency of mtDNA deletions, specifically the common 4977 bp deletion and ATPase deletions in infertile Iraqi males, and to evaluate their association with telomere length and mtDNA copy number. METHODS: A case–control study including 150 infertile males (Asthenozoospermia (AZ): Oligoasthenozoospermia (OAZ): Oligoasthenoteratozoospermia (OAT)) and 50 controls. Sperm cells were isolated using a density gradient centrifugation method followed by DNA extraction. Long PCR amplification and sequencing were used to detect deletions in mtDNA regions MTH1, MTH2, MTH3, and the ATPase gene. Telomere length and mtDNA copy number were measured and statistically analyzed to assess their relationship with the identified deletions. RESULTS: The highest mtDNA deletion rates in the MTH1 and MTH2 regions (14%) were observed in individuals with AZ and OAT, while the MTH3 region showed a 14.5% deletion frequency in OAT. The ATPase gene exhibited the highest deletion rate at 28.5% in this group. Correlation analyses demonstrated that deletions, particularly in MTH1 and ATPase, were associated with telomere shortening and increased mtDNA copy number. CONCLUSION: This study reveals a strong association between mtDNA deletions, increased mtDNA copy number, and telomere shortening in infertile males. These alterations are linked to impaired sperm quality, highlighting telomere length and mtDNA copy number as potential parameters and providing insights for future diagnostic approaches in male infertility.