{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T02:23:38Z","timestamp":1772850218105,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T00:00:00Z","timestamp":1609200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF2016-78722-R"],"award-info":[{"award-number":["SAF2016-78722-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["RYC-2014-16458"],"award-info":[{"award-number":["RYC-2014-16458"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["IJC2018-038026-I"],"award-info":[{"award-number":["IJC2018-038026-I"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/jpm11010022","type":"journal-article","created":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T10:04:46Z","timestamp":1609236286000},"page":"22","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Evaluation of Male Fertility-Associated Loci in a European Population of Patients with Severe Spermatogenic Impairment"],"prefix":"10.3390","volume":"11","author":[{"given":"Miriam","family":"Cerv\u00e1n-Mart\u00edn","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Universidad de Granada, 18016 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"}]},{"given":"Lara","family":"Bossini-Castillo","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Universidad de Granada, 18016 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"}]},{"given":"Roc\u00edo","family":"Rivera-Egea","sequence":"additional","affiliation":[{"name":"Andrology Laboratory and Sperm Bank, IVIRMA Valencia, 46015 Valencia, Spain"},{"name":"IVI Foundation, Health Research Institute La Fe, 46026 Valencia, Spain"}]},{"given":"Nicol\u00e1s","family":"Garrido","sequence":"additional","affiliation":[{"name":"IVI Foundation, Health Research Institute La Fe, 46026 Valencia, Spain"},{"name":"Servicio de Urolog\u00eda, Hospital Universitari i Politecnic La Fe e Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5005-3325","authenticated-orcid":false,"given":"Saturnino","family":"Luj\u00e1n","sequence":"additional","affiliation":[{"name":"Servicio de Urolog\u00eda, Hospital Universitari i Politecnic La Fe e Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6365-1087","authenticated-orcid":false,"given":"Gema","family":"Romeu","sequence":"additional","affiliation":[{"name":"Servicio de Urolog\u00eda, Hospital Universitari i Politecnic La Fe e Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"}]},{"given":"Samuel","family":"Santos-Ribeiro","sequence":"additional","affiliation":[{"name":"IVI-RMA Lisbon, 1800-282 Lisbon, Portugal"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, University of Lisbon, 1649-028 Lisbon, Portugal"}]},{"name":"IVIRMA Group","sequence":"additional","affiliation":[]},{"name":"Lisbon Clinical Group","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 A.","family":"Castilla","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"},{"name":"Unidad de Reproducci\u00f3n, UGC Obstetricia y Ginecolog\u00eda, HU Virgen de las Nieves, 18014 Granada, Spain"},{"name":"CEIFER Biobanco\u2014NextClinics, 18004 Granada, Spain"}]},{"given":"M. Carmen","family":"Gonzalvo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"},{"name":"Unidad de Reproducci\u00f3n, UGC Obstetricia y Ginecolog\u00eda, HU Virgen de las Nieves, 18014 Granada, Spain"}]},{"given":"Ana","family":"Clavero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"},{"name":"Unidad de Reproducci\u00f3n, UGC Obstetricia y Ginecolog\u00eda, HU Virgen de las Nieves, 18014 Granada, Spain"}]},{"given":"F. Javier","family":"Vicente","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"},{"name":"UGC de Urolog\u00eda, HU Virgen de las Nieves, 18014 Granada, Spain"}]},{"given":"Andrea","family":"Guzm\u00e1n-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Universidad de Granada, 18016 Granada, Spain"}]},{"given":"Cl\u00e1udia","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto (I3S), 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal"}]},{"given":"In\u00e9s","family":"Llinares-Burguet","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Universidad de Granada, 18016 Granada, Spain"}]},{"given":"Chiranan","family":"Khantham","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand"}]},{"given":"Miguel","family":"Burgos","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Universidad de Granada, 18016 Granada, Spain"}]},{"given":"Francisco J.","family":"Barrionuevo","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Universidad de Granada, 18016 Granada, Spain"}]},{"given":"Rafael","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Universidad de Granada, 18016 Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6489-3309","authenticated-orcid":false,"given":"Josvany","family":"S\u00e1nchez-Curbelo","sequence":"additional","affiliation":[{"name":"Laboratory of Seminology and Embryology, Andrology Service-Fundaci\u00f3 Puigvert, 08025 Barcelona, Spain"}]},{"given":"Olga","family":"L\u00f3pez-Rodrigo","sequence":"additional","affiliation":[{"name":"Laboratory of Seminology and Embryology, Andrology Service-Fundaci\u00f3 Puigvert, 08025 Barcelona, Spain"}]},{"given":"M. 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