Genetic Factors Contributing to the Development of Polymorphic Teratozoospermia in Humans

Non-specific (polymorphic) teratozoospermia is a common disorder of ejaculate quality in men, when the proportion of morphologically normal spermatozoa is below reference values, while the ejaculate specimen contains several types of morphological abnormalities of spermatozoa in different ratios. Polymorphic teratozoospermia can occur as a result of the influence of both negative environmental and lifestyle factors and the presence of pathogenic variants of some genes. However, little attention is paid to the study of the genetic causes of polymorphic teratozoospermia. This review, for the first time, is presenting the information on 85 pathogenic variants of 51 genes causing the development of polymorphic teratozoospermia in humans, which was collected and systematized from the analysis of published literature, as well as the data contained in the Malacards, OMIM, KEGG, CTD, DisGeNET databases. According to functional annotation of genes and analysis of published literature, the products of these genes participate in the organization of spermatid cytoskeleton components, the acroplaxome and perinuclear theca, which provide the formation of the acrosome and the interaction of the acrosomal vesicle with the nucleus, as well as intracellular transport of molecules, regulation of the protein expression and degradation, and the chromatin rearrangement during spermiogenesis. In addition, pathogenic variants of some genes lead to the decrease in the effectiveness of natural protection of cells against oxidative damage and, as a consequence, the manifestation of teratozoospermia. This information can be useful for diagnosis and selection of treatment tactics for polymorphic teratozoospermia, which can be caused by both genetic causes and the influence of negative environmental factors and lifestyle.