Publication:
Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility.

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Date

2022-10-28

Authors

Cervan-Martin, Miriam
Tüttelmann, Frank
Lopes, Alexandra M
Bossini-Castillo, Lara
Rivera-Egea, Rocio
Garrido, Nicolas
Lujan, Saturnino
Romeu, Gema
Santos-Ribeiro, Samuel
Castilla, Jose A

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Nature Publishing Group
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Abstract

We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DRβ1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition.

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MeSH Terms

Spermatogenesis
Sertoli Cells
Alleles
Protein Serine-Threonine Kinases
Intracellular Signaling Peptides and Proteins

DeCS Terms

Alelos
Células de Sertoli
Espermatogénesis
Proteínas serina-treonina quinasas
Péptidos y proteínas de señalización intracelular

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Keywords

Humans, Male, Genome-Wide Association Study, Infertility, Male

Citation

Cerván-Martín M, Tüttelmann F, Lopes AM, Bossini-Castillo L, Rivera-Egea R, Garrido N, et al. Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility. Commun Biol. 2022 Nov 10;5(1):1220.