Potential role of dynein‐related genes in the etiology of male infertility: A systematic review and a meta‐analysis

Abstract

Background The dynein‐related genes may have a role in the etiology of male infertility, particularly in cases of impaired sperm motility. Objectives The goal of this review is to compile a list of the most important dynein‐related candidate genes that may contribute to male factor infertility. Materials and methods Databases were searched using the keywords “dynein,” “male,” “infertility,” and by applying strict inclusion criteria. A meta‐analysis was also performed by using the eligible case‐control studies. The odd ratios (ORs), the Z‐test score, and the level of significance were determined using a fixed model with a p value of 0.05. Funnel plots were used to check for publication bias. Results There were 35 studies that met the inclusion criteria. There were a total of 15 genes responsible for the production of dynein structural proteins, the production of dynein assembling factors, and potentially associated with male infertility. A total of five case‐control studies were eligible for inclusion in the meta‐analysis. Variants in the dynein‐related genes were linked to an increased the risk of male infertility (OR = 21.52, 95% confidence interval 8.34–55.50, Z test = 6.35, p < 0.05). The percentage of heterogeneity, I2, was 47.00%. The lack of variants in the dynein genes was an advantage, and this was statistically significant. Discussion The results from the present review illustrate that pathogenic variants in genes both for dynein synthesis and for dynein assembly factors could be associated with isolated cases of male infertility without any other symptoms. Conclusions The genes addressed in this study, which are involved in both the production and assembly of dynein, could be used as molecular targets for future research into the etiology of sperm motility problems.

The human sperm proteome—Toward a panel for male fertility testing

“…As a basic cytoskeleton protein of the mammalian sperm head, absence or dysregulation of CCIN is known to cause sperm malformation 122 . Relevance for proper flagellum formation and functioning is further inherent to three cilia and flagella‐associated proteins (CFAP47, CFAP65, CFAP251/WDR66) and DNAH1 42,43,45,46,91,123,124 . Nevertheless, all sperm proteins in Table 1 could be implicated in the development of male fertility disorders, and hence might be further evaluated for their potential as male fertility markers.…”

“…122 Relevance for proper flagellum formation and functioning is further inherent to three cilia and flagella-associated proteins (CFAP47, CFAP65, CFAP251/WDR66) and DNAH1. 42,43,45,46,91,123,124 Nevertheless, all sperm proteins in Table 1 could be implicated in the development of male fertility disorders, and hence might be further evaluated for their potential as male fertility markers. In support of such utilization, the coding genes of 18 out of the 31 validated candidate markers are already included in an 81 gene panel (ID192.04) for male fertility testing (e.g., www.zhma.de).…”

ZMYND12 serves as an IDAd subunit that is essential for sperm motility in mice

“…The loss of DNAH1 function was the rst such variant that was conclusively identi ed as a cause of MMAF cases of AZS [15]. More recently, studies have documented links between male fertility and a range of dynein proteins including DNAH2, with many variants in these genes having been linked to MMAF symptoms [37]. A recent report documented an association between MMAF incidence and ZMYND12 truncating and frameshift variants [21].…”

Single-cell transcriptome unravels spermatogonial stem cells and dynamic heterogeneity of spermatogenesis in seasonal breeding teleost

“…Those genes also play essential roles in spermiogenesis in mammals (Levkova et al, 2022;Priyanka and Yenugu, 2021;Tang et al, 2017), indicating that the essential genes for spermiogenesis are conserved in vertebrates.…”