Lack of association between single polymorphic variants of the mitochondrial nicotinamide adenine dinucleotide dehydrogenase 3, and 4L (MT‐ND3andMT‐ND4L) and male infertility

Abstract

Male infertility is a multifactorial condition associated with different genetic abnormalities in at least 15%–30% of cases. The purpose of this study was to identify suspected correlations between infertility and polymorphisms in mitochondrial NADH dehydrogenase subunits 3 and 4L (MT‐ND3 and MT‐ND4L) in subfertile male spermatozoa. Sanger sequencing of the mitochondrial DNA target genes was performed on 68 subfertile and 44 fertile males. Eight single nucleotide polymorphisms (SNPs) in MT‐ND3 (rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954) and seven SNPs in MT‐ND4L (rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881) were detected and genotyped. The genotypes and allele frequencies of the study population have shown a lack of statistically significant association between MT‐ND3 and MT‐ND4L SNPs and male infertility. However, no statistically significant association was found between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia and oligoteratozoospermia subgroups of subfertile males. However, rs28358278 genotype of the MT‐ND3 gene was reported in the subfertile group but not in the fertile group, which implies a possible role of this SNP in male infertility. In conclusion, the investigated polymorphic variants in the MT‐ND3 and MT‐ND4L genes did not show any significant association with the occurrence of male infertility. Further studies are required to evaluate these findings. Moreover, the subfertile individuals who exhibit a polymorphism at rs28358278 require further monitoring and evaluation.

A two-sample mendelian randomization analysis investigates associations between gut microbiota and infertility

“…Dysbiosis-induced dysregulation of the intestinal flora also causes decreased expression of the Ggnbp2 gene, which is crucial for repairing meiotic DNA double-strand breaks in spermatocytes, consequently inhibiting spermatogenesis 34 . Moreover, reduced expression of the genes encoding core subunits of the respiratory chain on mitochondrial membranes, including MT-ND1, MT-ND2, MT-ND4, MT-ND5 and MT-ND4L, leads to increased sperm mitochondrial membrane potential and decreased sperm motility 35 – 37 . Furthermore, the diminished expression of the Crisp2 gene, essential for regulating Ca 2+ influx during sperm capacitation and motility, has adverse effects on sperm motility 38 .…”

A lack of a definite correlation between male sub-fertility and single nucleotide polymorphisms in sperm mitochondrial genes MT-CO3, MT-ATP6 and MT-ATP8

“…Moreover, studying genetic variations such as SNPs might be a helpful genetic analysis to understand the molecular bases of idiopathic infertility in males. In many studies, certain SNPs have shown an association with certain disorders such as cancer and infertility [24]. This work aimed to investigate whether there was an association between polymorphisms in the mitochondrial genes MT-CO3, MT-ATP6 and MT-ATP8 and male subfertility.…”

“…Spermatozoa with defective mitochondria produce insufficient ATP and have elevated levels of reactive oxygen species (ROS) or free radicals. In an imbalanced system, the production of ROS and free radicals would cause significant damage to the mitochondria and mtDNA, affecting sperm motility and finally leading to male infertility [ 24 ]. More specifically, an inadequate molecular profile of all types of male infertility still remains.…”

“…Moreover, studying genetic variations such as SNPs might be a helpful genetic analysis to understand the molecular bases of idiopathic infertility in males. In many studies, certain SNPs have shown an association with certain disorders such as cancer and infertility [ 24 ].…”

A Systematic Review of the Impact of Mitochondrial Variations on Male Infertility

“…Recently, we scanned sterile and fertile males for polymorphisms by the direct sequencing of MTND3 , MTND4L , and MTND4 genes in our laboratory [ 108 ].…”