Evaluation of male fertility-associated loci in a european population of patients with severe spermatogenic impairment

Miriam Cerván-Martín, Lara Bossini-Castillo, Rocío Rivera-Egea, Nicolás Garrido, Saturnino Luján, Gema Romeu, Samuel Santos-Ribeiro, José A. Castilla, M. Carmen Gonzalvo, Ana Clavero, F. Javier Vicente, Andrea Guzmán-Jiménez, Cláudia Costa, Inés Llinares-Burguet, Chiranan Khantham, Miguel Burgos, Francisco J. Barrionuevo, Rafael Jiménez, Josvany Sánchez-Curbelo, Olga López-RodrigoM. Fernanda Peraza, Iris Pereira-Caetano, Patricia I. Marques, Filipa Carvalho, Alberto Barros, Lluís Bassas, Susana Seixas, João Gonçalves, Sara Larriba, Alexandra M. Lopes, Rogelio J. Palomino-Morales, F. David Carmona

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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.

Original languageEnglish
Article number22
Pages (from-to)1-19
Number of pages19
JournalJournal of Personalized Medicine
Issue number1
Publication statusPublished - Jan 2021


  • Genetic association analysis
  • Impaired spermatogenesis
  • Infertility
  • Non-obstructive azoospermia
  • Severe oligospermia
  • SNPs


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