Impact of Mitochondrial Genetic Variants in ND1, ND2, ND5, and ND6 Genes on Sperm Motility and Intracytoplasmic Sperm Injection (ICSI) Outcomes

Abstract

Sperm mitochondrial dysfunction causes the generation of an insufficient amount of energy needed for sperm motility. This will affect sperm fertilization capacity, and thus, most asthenozoospermic men usually require assisted reproductive techniques. The etiology of asthenozoospermia remains largely unknown. The current study aimed to investigate the effect of mitochondrial genetic variants on sperm motility and intracytoplasmic sperm injection (ICSI) outcomes. A total of 150 couples from the ICSI cycle were enrolled in this study. One hundred five of the male partners were asthenozoospermic patients, and they were subdivided into three groups according to their percentage of sperm motility, while forty-five of the male partners were normozoospermic. Genetic variants were screened using direct Sanger’s sequencing in four mitochondrial genes (nicotinamide adenine dinucleotide hydrogen (NADH) dehydrogenase 1 (ND1), NADH dehydrogenase 2 (ND2), NADH dehydrogenase 5 (ND5), and NADH dehydrogenase 6 (ND6)). We identified three significant variants: 13708G>A (rs28359178) in ND5, 4216T>C (rs1599988) in ND1, and a novel 12506T>A in ND5 with P values 0.006, 0.036, and 0.013, respectively. The medians of sperm motility, fertilization rate, embryo cleavage score, and embryo quality score were significantly different between men showing 4216T>C, 12506T>A, 13708G>A and wild type, Mann-Whitney P values for the differences in the medians were < 0.05 in all of them. The results from this study suggest that 13708G>A, 12506T>A, and 4216 T>C variants in sperm mitochondrial DNA negatively affect sperm motility and ICSI outcomes.

Association between the single nucleotide variants of the mitochondrial cytochrome B gene (MT-CYB) and the male infertility

“…Besides, two studies were conducted in our laboratory, the first study demonstrated that the frequencies of total mitochondrial variants in four mitochondrial genes (nicotinamide adenine dinucleotide hydrogen (NADH) dehydrogenase 1 (ND1), NADH dehydrogenase 2 (ND2), NADH dehydrogenase 5 (ND5), and NADH dehydrogenase 6 (ND6)) were negatively correlated with the percentages of sperm motility and ICSI outcomes, namely 13708 G>A, 4216T>C and 12506T>A [5,33]. Mughal et al discovered that mtDNA mutations had a major impact on sperm production, resulting in infertility, by influencing various sperm motility parameters [34].…”

“…Mitochondrial mutations are very common etiological pathogenic factors in energy-demanding organs such as muscles and the nervous system and are related to musculoskeletal and neurodegenerative disorders [ 4 ]. In addition, genetic alteration in the mtDNA may have significant effects on normal spermatogenesis and subsequently on fertilization [ 5 , 6 ]. Several reports have shown that mitochondrial dysfunction could lead to complete or partial spermatogenesis arrest and be an important causative factor in male infertility [ 7 ].…”

The genetic causes of male infertility: a Middle East and North Africa perspective

“…A proposed solution for such infertility is ICSI. Studies now show that although mitochondrial DNA variation has a negative impact on ICSI outcomes, it is still possible (Al Smadi et al 2021). Sperm DNA integrity is one of the vital prognostic factors of male fertility.…”

Elevated seminal protein carbonyl concentration is correlated with asthenozoospermia and affects adversely the laboratory intracytoplasmic sperm injection (ICSI) outcomes

“…Patients with varicocele, alcoholic problems and cigarette smokers and patients with age above 40 were excluded from this study. Semen collection, sperm preparation for ICSI, oocyte denudation, the (ICSI) technique, fertilisation assessment, embryo grading, embryo cleavage score and embryo quality score were described previously (Al Smadi et al., 2021). This study was approved by the Jordanian Royal Medical Services‐Human Research Ethics Committee on 30/7/2018 (TF3/1/Ethics Committee/9,126).…”