Mitochondrial nicotinamide adenine dinucleotide hydride dehydrogenase (NADH) subunit 4 (MTND4) polymorphisms and their association with male infertility

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

doi:10.1007/s10815-021-02199-w

Cited by 6 publications

(3 citation statements)

References 46 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background Idiopathic male infertility can be attributed to genetic predispositions that affect sperm performance and function. Genetic alterations in the mitochondrial DNA (mtDNA) have been linked to certain types of male infertility and abnormal sperm function. Mutations in the mitochondrial cytochrome B (MT-CYB) gene might lead to some deficiencies in mitochondrial function. Thus, in the current study, we aimed to investigate the effect of mutations in the MT-CYB gene on sperm motility and male infertility. Methods and results Semen specimens were collected from 111 men where 67 men were subfertile and 44 were fertile. QIAamp DNA Mini Kit and REPLI-g Mitochondrial DNA Kit from QIAGEN were used to isolate and amplify the mitochondrial DNA. Followed by PCR and Sanger sequencing for the target sequence in the MT-CYP gene. Sequencing of the MT-CYB gene revealed a total of thirteen single nucleotide polymorphisms (SNPs). Eight SNPs were non-synonymous variant (missense variant) including: rs2853508, rs28357685, rs41518645, rs2853507, rs28357376, rs35070048, rs2853506, and rs28660155. While five SNPs were Synonymous variant: rs527236194, rs28357373, rs28357369, rs41504845, and rs2854124. Among these SNPs, three variants showed a significant difference in the frequency of the genotypes between subfertile and fertile groups: rs527236194 (T15784C) (P = 0.0005), rs28357373 (T15629C) (P = 0.0439), and rs41504845 (C15833T) (P = 0.0038). Moreover, two SNPs showed a significant association between allelic frequencies of rs527236194 (T15784C) (P = 0.0014) and rs41504845 (C15833T) (P = 0.0147) and male subfertility. Conclusion The current study showed a significant association between the MT-CYB gene polymorphisms and the development of male infertility. In particular, rs527236194, rs28357373 and rs41504845 variants were found to be the most related to the subfertility group. Further studies on larger and other populations are required to reveal the exact role of this gene in the development of male infertility. In addition, functional studies will be helpful to elucidate the molecular impact of the MT-CYP polymorphisms on mitochondrial function.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, G11719A (rs2853495) and A11251G (rs869096886) in gene MTND4 were also tied to male infertility. Therefore, even if the genotype of the allele is different, the presence of the allele itself could still be tied to male infertility [ 109 ].…”

Section: Mitochondrial Genome Mutations/variations and Male Infertilitymentioning

confidence: 99%

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

Amor

Hammadeh

2022

Genes

Self Cite

View full text Add to dashboard Cite

According to current estimates, infertility affects one in four couples trying to conceive. Primary or secondary infertility can be due either to both partners or only to the man or the woman. Up to 15% of infertility cases in men can be attributed to genetic factors that can lead to irreversible partial or complete spermatogenic arrest. The increased use of assisted reproductive technology (ART) has provided not only insights into the causes of male infertility but also afforded a diagnostic tool to detect and manage this condition among couples. Genes control a variety of physiological attributes, such as the hypothalamic–pituitary–gonadal axis, development, and germ cell differentiation. In the era of ART, it is important to understand the genetic basis of infertility so as to provide the most tailored therapy and counseling to couples. Genetic factors involved in male infertility can be chromosome abnormalities or single-gene disorders, mitochondrial DNA (mtDNA) mutations, Y-chromosome deletions, multifactorial disorders, imprinting disorders, or endocrine disorders of genetic origin. In this review, we discuss the role of mitochondria and the mitochondrial genome as an indicator of sperm quality and fertility.

show abstract

“…Previous studies have demonstrated a strong association between impaired mtDNA and the development of male infertility conditions such as asthenozoospermia, oligozoospermia and teratozoospermia (Dahadhah et al, 2021). For instance, large-scale deletions in the mtDNA were reported in asthenozoospermia in different populations (Al Zoubi et al, 2020;Bahrehmand Namaghi & Vaziri, 2017;Kao et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Mitochondrial nicotinamide adenine dinucleotide hydride dehydrogenase (NADH) subunit 4 (MTND4) polymorphisms and their association with male infertility

Cited by 6 publications

References 46 publications

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

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

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

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

Contact Info

Product

Resources

About