The genetic causes of male infertility: a Middle East and North Africa perspective

Abstract

Male infertility is attributable to 60% of total infertility cases and about 30-50% of these cases remain idiopathic. In the Middle East and North Africa region (MENA), male infertility affects about 22.6% of men of reproductive age. Male infertility is caused by a variety of factors, including endocrine disruption, exposure to toxins, lifestyle, genetic and epigenetic modifications. Genetic modifications, including chromosomal abnormalities, chromosomal rearrangements, Y chromosome microdeletions and single-gene mutations, explain for about 10-15% of infertility cases. Since genetic aberration is a key player in the pathogenesis of male infertility, it is important to explore the impact in the MENA region due to the high incidence of male infertility. Therefore, the current study aims to systematically analyse the literature regarding the impact and common causes of male infertility in the MENA region. To achieve this aim, a comprehensive literature search was performed on PubMed, Google Scholar, and Science Direct databases. Following the search, a total of 126 articles was retrieved, of which 12 were duplicates and another 69 articles did not meet the inclusion criteria, totaling the exclusion of 81 articles. Studies excluded were those that had patient populations originating outside the MENA region, review articles, non-English written articles, or studies where the patient population was under 18 years of age. Findings showed that the frequent genetic aberration leading to male infertility in these regions include Y chromosome microdeletions, gene polymorphisms or copy number variations, mitochondrial microdeletions and other genetic deletions or mutations. In lieu of this, diverse clinical genetic tests should be made available for the proper diagnosis of male infertility.

Keywords: MENA; chromosomal abnormalities; gene deletion; gene mutation; Y chromosome microdeletion.; male infertility.

Figure 1.. Schematic representation of the search method.

Following the search from different databases, a total of 126 articles was retrieved, of which 12 were duplicates and another 69 articles did not meet the inclusion criteria. Studies excluded were those that had patient populations originating outside the MENA region, review articles, non-English written articles, or studies where the patient population was under 18 years of age.

Figure 2.. Distribution of MENA studies according to the genetic alteration.

From our findings, the following are the common genetic abnormalities found in the MENA region: (i) Y chromosome microdeletion, (ii) deletion or gene mutation, (iii) gene polymorphism or copy number variations, (iv) chromosomal disorders, and (v) mitochondrial mutation.

Figure 3.. Diagram of the Y Chromosome.

The Y chromosome is an acro-centric form of chromosome, with its centromere located severely off the center. It is divided into the long arm (Yq) and the short arm (Yp). The Yp and the proximal part of the Yq forms the Euchromatin, also known as the Yq11, and the distal part of Yq forms the Heterochromatin (Yq12). The pseudoautosomal region (PAR) represent where the Y chromosome binds with the X chromosome, and the AZF regions are located on the Yq. It is important to note that the length of the heterochromatin varies.