Assessment of correlation between asthenozoospermia and mitochondrial DNA mutations in Egyptian infertile men

Abstract

Background Asthenozoospermia is a chief reason for male seminal pathologies with an impression of around 19% of infertile patients. Spermatozoa mitochondrial DNA variations seem to link with low sperm motility. The objective of the study was to assess the relation between mitochondrial mutations and male sterility, especially in asthenozoospermia. The patient semen samples were investigated by studying the sperm physical characters; motility, viability, and morphological parameters were then classified into normozoospermia and asthenozoospermia. In addition, the level of malondialdehyde (MDA) as a bio-indicator of lipid peroxidation, seminal fructose, and total antioxidant capacity (TAC) were estimated. For molecular analysis, DNA from the semen samples was extracted using a DNA extraction kit. ND1, ND2, and ATPase6 genes were amplified by using a specific primer. After the purification procedure, each PCR product was sequenced to identify the single nucleotide polymorphisms (SNPs) in selected genes. Results A significant negative correlation between seminal plasma malondialdehyde levels and sperm motility was detected. Meanwhile, TAC analysis revealed significantly lower activity (p ≤ 0.05) in the sample of asthenozoospermic than in normozoospermic men. As regards the seminal plasma fructose, there was no significant difference in the fructose level of normozoospermia and asthenozoospermia cases. At the molecular level, 31 diverse nucleotide substitutions were recognized in mitochondrial DNA. Only ten (10) mutations led to amino acid transformation: four have deleterious effects, four are benign, and the other two have conflicting effectiveness. Conclusions This study is the first in Egypt that is concerned with studying the relationship between the mitochondrial DNA mutations in human spermatozoa of asthenozoospermic patients and fertility. The results displayed scientific indications evidenced that there is an association between mitochondrial mutations and male infertility.

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

“…The rs2001031 (A8860G) and rs2000975 (A8701) were reported by a current study in which they were found to make a change in the amino acid sequence from threonine to Alanine and they were signi cantly associated with asthenozoospermia. In this study, we have reported the same SNPs but statistically, they were not calculated as signi cant variations although they both cause a missense variation in the coding portion (Abd Elrahman et al, 2021).…”

“…Reactive oxygen species (ROS) are byproducts of the mitochondrial respiratory chain, the mutation rate generated by ROS is 10-100 times greater than nuclear DNA because the mitochondrial DNA is located in the mitochondrial matrix (Shamsi et al, 2008). The mammalian sperm consists of about 22 to 75 mitochondria located in the midpiece of the sperm, ensuring proper function of the agella and normal sperm motility for an e cient fertilization process (Abd Elrahman et al, 2021). Therefore, any genetic alteration of this limited number of mitochondria can be related to the improper function of the sperm.…”

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

“…A recent study revealed five non-synonymous SNPs in nicotinamide adenine dinucleotide hydrogen (NADH) dehydrogenase 1 gene (ND1) located at nucleotides T3398C, T3821C, G4048A, T4169TT, and T4216C. Since secondary structure prediction of T3398C and T3821C proteins revealed a negative change in protein function, these alterations could result in sperm motility decline and male infertility [ 32 ].…”

In-silico molecular characterization of DNAH6 and ATPase6 (Mitochondrial DNA) genes in asthenozoospermia patients in the northern region of India

“…Genetic factors involved in male infertility manifest as chromosomal disorders, mitochondrial DNA (mtDNA) mutations, monogenic disorders, multifactorial disorders, and endocrine disorders of genetic origin. Male infertility is often related to chromosome abnormalities or other genetic factors (Holyoake et al 2002;Nakada et al 2006; Elrahman et al 2021;Thomas et al 2021). DNAH6 (Dynein Axonemal Heavy Chain 6) is a protein-coding gene, part of the microtubule-associated motor protein and is a testis-speci c-expressed protein, located in the neck region of the spermatozoa, required for the function of cilia function in spermatozoa (Li et al 2017).…”