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

Mohammad A Al Smadi,Mohammad M Altalib,Mohammad Y Jahmani,Erich Solomayer,Bassam Nusair,Mohamad Eid Hammadeh,Mohammad A Shboul,Osamah Batiha,Houda Amor

doi:10.1007/s43032-020-00449-3

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.

Highlights

Genetic variants in mitochondrial genes are associated with many diseases [1]
Sperm depends on the mitochondrial oxidative phosphorylation (OxPhos) mechanism to produce the required energy for its motility [6]; mutated mitochondrial DNA (mtDNA) leads to energy insufficiency, which causes a reduction in sperm motility [7]
Statistical analysis was carried out using the OriginPro, Version 2020 (OriginLab Corporation, Northampton, MA, USA)

Summary

Introduction

Genetic variants in mitochondrial genes are associated with many diseases [1]. Most of these diseases affect organs withScience and Technology, Irbid, Jordan 5 Reproductive Endocrinology and IVF Unit, King Hussein MedicalCentre, Amman, Jordan high energy demand, such as the brain, the skeletal muscle, the eye, and the heart [2]. Genetic variants in mitochondrial genes are associated with many diseases [1]. Most of these diseases affect organs with. The mtDNA repair mechanism is less efficient compared to nuclear DNA repair [4]. Together, these factors increase the mutation rate in mtDNA, compared to nuclear DNA by 10–100 times [5]. Sperm depends on the mitochondrial oxidative phosphorylation (OxPhos) mechanism to produce the required energy for its motility [6]; mutated mtDNA leads to energy insufficiency, which causes a reduction in sperm motility [7]. In comparison to the oocyte, which has around 150,000 mtDNA copies, the spermatozoa have only around 100 mtDNA copies [8]

Objectives

Methods

Results

Discussion

Conclusion