A Catalog of Human Genes Associated With Pathozoospermia and Functional Characteristics of These Genes

Abstract

Genetic causes of the global decline in male fertility are among the hot spots of scientific research in reproductive genetics. The most common way to evaluate male fertility in clinical trials is to determine semen quality. Lower semen quality is very often accompanied by subfertility or infertility, occurs in many diseases and can be caused by many factors, including genetic ones. The following forms of lowered semen quality (pathozoospermia) are known: azoospermia, oligozoospermia, asthenozoospermia, teratozoospermia, and some combined forms. To systematize information about the genetic basis of impaired spermatogenesis, we created a catalog of human genes associated with lowered semen quality (HGAPat) and analyzed their functional characteristics. The catalog comprises data on 126 human genes. Each entry of the catalog describes an association between an allelic variant of the gene and a particular form of lowered semen quality, extracted from the experimental study. Most genes included into the catalog are located on autosomes and are associated with such pathologies as non-obstructive azoospermia, oligozoospermia or asthenozoospermia. Slightly less than half of the included genes (43%) are expressed in the testes in a tissue-specific manner. Functional annotation of genes from the catalog showed that spermatogenic failure can be associated with mutations in genes that control biological processes essential for spermiogenesis (regulating DNA metabolism, cell division, formation of cellular structures, which provide cell movement) as well as with mutations in genes that control cellular responses to unfavorable conditions (stress factors, including oxidative stress and exposure to toxins).

Keywords: catalog of genes; genetic polymorphism; infertility; male fertility; pathozoospermia; spermatogenesis.

FIGURE 1

Informational content of the catalog HGAPat. (A) HGAPat statistics. Queries to databases were performed according to the scheme presented in Supplementary Figure 1. (B) Chromosomal localization of genes. MT stands for genes, located in mitochondrial DNA. (C) The number of genes associated with a specific form of pathozoospermia (NOA, non-obstructive azoospermia). When calculating the number of genes associated with Teratozoospermia, genes associated with Globozoospermia were taken into account. (D) Proportion of genes, expressed in a testis-specific or testis-enriched manner.

FIGURE 2

Representative terms from the Gene Ontology database which, according to DAVID, are overrepresented (FDR < 5 * 10^–2) in the annotations of genes from the catalog HGAPat.

FIGURE 3

Genes from the catalog HGAPat associated with GO terms designating response to unfavorable conditions (these terms are presented in rectangular boxes). The numbers indicate the number of genes in each group. Genes that are expressed in testis-enriched or testis-specific manner are shown in black; the other genes are shown in red.

FIGURE 4

Genes from the catalog associated with various forms of sperm abnormalities. The forms of pathozoospermia are presented in rectangular frames. Combined forms of pathozoospermia are shown in black and italics. The numbers in each part of the circles indicate the numbers of genes in each group. The blue ovals show the percentage of genes that control the response to adverse factors (response to oxidative stress, response to oxygen-containing compound, response to stress, response to toxic substance). Genes that are expressed in testis-enriched or testis-specific manner are shown in black; the other genes are shown in red.