Lack of association between single polymorphic variants of the mitochondrial nicotinamide adenine dinucleotide dehydrogenase 3, and 4L (MT-ND3 and MT-ND4L) and male infertility.

Fatina W Dahadhah,Houda Amor,Mayyas Saleh Jaweesh,Mohamad Eid Hammadeh,Manal Issam Abu Alarjah,Mazhar Salim Al Zoubi

doi:10.1111/and.14139

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.

Highlights

Malefactors represent up to 50% of couples' infertility worldwide (De Kretser & Baker, 1999; Navarro-Costa et al, 2010)
The sperm efficiency to fertilise the ovum is related to the energy level which is provided by the mitochondria
MtDNA is more vulnerable compared to nuclear DNA due to the lack of an efficient repairing system and high exposure to oxidative species produced by the mitochondria

Summary

| INTRODUCTION

Malefactors represent up to 50% of couples' infertility worldwide (De Kretser & Baker, 1999; Navarro-Costa et al, 2010). MtDNA is more vulnerable compared to nuclear DNA due to the lack of an efficient repairing system and high exposure to oxidative species produced by the mitochondria This leads to abnormal sperm function, structure and even infertility (Hsia et al, 2003; Nakane et al, 2008). Other genetic alterations have been suggested to be related to idiopathic male infertility including metabolic and structural enzymes such as methylenetetrahydrofolate reductase (MTHFR) and cystic fibrosis transmembrane conductance regulator (CFTR) (Cuppens & Cassiman, 2004; Wei et al, 2012). Elevated levels of homocysteine as well polymorphisms in the MTHFR gene were reported to have an association with male infertility in several populations (Dhillon et al, 2007; Lee et al, 2006; Mfady et al, 2014; Tetik et al, 2008). We aimed to elucidate the possible association between the MT-ND3 and MT- ND4L genes’ polymorphisms and the development of male infertility

| MATERIALS AND METHODS

Findings

| DISCUSSION