Evaluation of Male Fertility-Associated Loci in a European Population of Patients with Severe Spermatogenic Impairment
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AuthorCerván-Martín, Miriam; Bossini Castillo, Lara María; Guzmán Jiménez, Andrea; Llinares Burguet, Inés; Burgos Poyatos, Miguel; Barrionuevo Jiménez, Francisco Javier; Jiménez Medina, Rafael; Palomino Morales, Rogelio Jesús
SNPsGenetic association analysisImpaired spermatogenesisNon-obstructive azoospermiaSevere oligospermiaInfertility
Cerván-Martín, M.; Bossini-Castillo, L.; Rivera-Egea, R.; Garrido, N.; Luján, S.; Romeu, G.; Santos-Ribeiro, S.; Castilla, J.A.; Gonzalvo, M.C.; Clavero, A.; et al. Evaluation of Male Fertility-Associated Loci in a European Population of Patients with Severe Spermatogenic Impairment. J. Pers. Med. 2021, 11, 22. https://doi.org/10.3390/jpm11010022
SponsorshipSpanish Ministry of Economy and Competitiveness through the Spanish State Plan for Scientific and Technical Research and Innovation SAF201678722-R; Spanish Government RYC-2014-16458; "Juan de la Cierva Incorporacion" program IJC2018-038026-I; European Union (EU); Spanish Government FIS-ISCIII DTS18/00101; Generalitat de Catalunya 2017SGR191; "Plan Propio" program of the University of Granada ("Becas de Iniciacion a la Investigacion para estudiantes de Grado"); "Researchers Consolidation Program" from the SNS-Dpt. Salut Generalitat de Catalunya CES09/020; FCT/MCTES, through national funds attributed to Center for Toxicogenomics and Human Health-ToxOmics UIDB/00009/2020; Portuguese Foundation for Science and Technology SFRH/BPD/120777/2016; Portuguese State Budget of the Ministry for Science, Technology and High Education; European Social Fund through the Programa Operacional do Capital Humano; Portuguese Foundation for Science and Technology IF/01262/2014; FCT in the framework of the project "Institute for Research and Innovation in Health Sciences" POCI-01-0145-FEDER-007274
Infertility is a growing concern in developed societies. Two extreme phenotypes of male infertility are non-obstructive azoospermia (NOA) and severe oligospermia (SO), which are characterized by severe spermatogenic failure (SpF). We designed a genetic association study comprising 725 Iberian infertile men as a consequence of SpF and 1058 unaffected controls to evaluate whether five single-nucleotide polymorphisms (SNPs), previously associated with reduced fertility in Hutterites, are also involved in the genetic susceptibility to idiopathic SpF and specific clinical entities. A significant difference in the allele frequencies of USP8-rs7174015 was observed under the recessive model between the NOA group and both the control group (p = 0.0226, OR = 1.33) and the SO group (p = 0.0048, OR = 1.78). Other genetic associations for EPSTI1-rs12870438 and PSAT1-rs7867029 with SO and between TUSC1-rs10966811 and testicular sperm extraction (TESE) success in the context of NOA were observed. In silico analysis of functional annotations demonstrated cis-eQTL effects of such SNPs likely due to the modification of binding motif sites for relevant transcription factors of the spermatogenic process. The findings reported here shed light on the molecular mechanisms leading to severe phenotypes of idiopathic male infertility, and may help to better understand the contribution of the common genetic variation to the development of these conditions.