Investigating the Molecular Basis of Immotile Sperms and Azoospermia Associated with Male Infertility in Palestinian Individuals

John Edward Tawil
جون إدوارد طويل.
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Al-Quds University
Infertility in men seems to be very obscure and lacks appropriate explanations in terms of genetic causes, though as a definition infertility, in general, is the inability of couples to conceive within a year of trying to achieve pregnancy without using contraceptives. Considerations in the definition means that the male is incapable of producing healthy sperms and/or sometimes no sperms at all that can fertilize an egg. The quality and the quantity of the produced sperms is very important, and a sperm should owe to specific criteria in order to be fertile, it needs a good tail or flagellum that can provide capacity to move, a good head that provide capacity to penetrate the egg in a quick manner and enough mitochondria in the neck, all with an integrated morphological feature and avide quantity. In term of Quality for instance, Multiple morphological abnormalities of the sperm flagellum (MMAF) is a disorder that results in the inability of sperm to move effectively. It encompasses a range of flagellar disorders. The genetic basis of MMAF is complex and could be owed to multiple genes. And, in terms of quantity oligospermia and azoospermia refer to decreased sperm quantity, which plays a critical role in increasing the chances of conception. Advances in genetic and molecular research are helping to address this issue and improve reproductive outcomes. In Palestinian community investigation is worthy because we have many consanguineous marriages which is set at a rate of ~ 40% this is according to the central bureau of Statistics in Palestine, which may help in finding variations in genes associated to MMAF that is not related to environmental factors. In this study, we utilized whole exome sequencing (WES) to analyze two independent individuals with different forms of infertility: asthenospermia and non-obstructive azoospermia. Our WES analysis led to the identification of several candidate genetic variations that may contribute to these phenotypes. In the asthenospermia case, we identified variants in four candidate genes (MROH8, MUC4, FADS6, TAS2R43) that may explain the MMAF phenotype. In the azoospermia case, we identified a homozygous missense variation in the MDM1 gene (NM_017440.4: c.1981G>A: p.Ala661Thr), which may explain the observed spermatogenesis failure. Segregation analysis revealed that the affected brother of the proband is also homozygous for the same MDM1, further supporting its potential role in the azoospermia observed in this family. Additionally, we identified variations in other four candidate genes (MAGEC1, OSBP2, NAT10, CD248) in the azoospermia case that may also play a role in infertility. We believe that there are still many unknown genes that causes azoospermia and asthenospermia. Trying to find a signature that exist in our Palestinian community would make innovative solutions in the future in the world of genetics practical.