Frontiers in Cell and Developmental Biology (Dec 2022)

Contribution of TEX15 genetic variants to the risk of developing severe non-obstructive oligozoospermia

  • Andrea Guzmán-Jiménez,
  • Andrea Guzmán-Jiménez,
  • Sara González-Muñoz,
  • Sara González-Muñoz,
  • Miriam Cerván-Martín,
  • Miriam Cerván-Martín,
  • Rocío Rivera-Egea,
  • Rocío Rivera-Egea,
  • Nicolás Garrido,
  • Nicolás Garrido,
  • Saturnino Luján,
  • Samuel Santos-Ribeiro,
  • Samuel Santos-Ribeiro,
  • José A. Castilla,
  • José A. Castilla,
  • José A. Castilla,
  • M. Carmen Gonzalvo,
  • M. Carmen Gonzalvo,
  • Ana Clavero,
  • Ana Clavero,
  • F. Javier Vicente,
  • F. Javier Vicente,
  • Vicente Maldonado,
  • Javier Villegas-Salmerón,
  • Miguel Burgos,
  • Rafael Jiménez,
  • Maria Graça Pinto,
  • Isabel Pereira,
  • Joaquim Nunes,
  • Josvany Sánchez-Curbelo,
  • Olga López-Rodrigo,
  • Iris Pereira-Caetano,
  • Patricia Isabel Marques,
  • Patricia Isabel Marques,
  • Filipa Carvalho,
  • Filipa Carvalho,
  • Alberto Barros,
  • Alberto Barros,
  • Lluís Bassas,
  • Susana Seixas,
  • Susana Seixas,
  • João Gonçalves,
  • João Gonçalves,
  • Alexandra M. Lopes,
  • Alexandra M. Lopes,
  • Sara Larriba,
  • Rogelio J. Palomino-Morales,
  • Rogelio J. Palomino-Morales,
  • F. David Carmona,
  • F. David Carmona,
  • Lara Bossini-Castillo,
  • Lara Bossini-Castillo,
  • IVIRMA Group,
  • Lisbon Clinical Group

DOI
https://doi.org/10.3389/fcell.2022.1089782
Journal volume & issue
Vol. 10

Abstract

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Background: Severe spermatogenic failure (SPGF) represents one of the most relevant causes of male infertility. This pathological condition can lead to extreme abnormalities in the seminal sperm count, such as severe oligozoospermia (SO) or non-obstructive azoospermia (NOA). Most cases of SPGF have an unknown aetiology, and it is known that this idiopathic form of male infertility represents a complex condition. In this study, we aimed to evaluate whether common genetic variation in TEX15, which encodes a key player in spermatogenesis, is involved in the susceptibility to idiopathic SPGF.Materials and Methods: We designed a genetic association study comprising a total of 727 SPGF cases (including 527 NOA and 200 SO) and 1,058 unaffected men from the Iberian Peninsula. Following a tagging strategy, three tag single-nucleotide polymorphisms (SNPs) of TEX15 (rs1362912, rs323342, and rs323346) were selected for genotyping using TaqMan probes. Case-control association tests were then performed by logistic regression models. In silico analyses were also carried out to shed light into the putative functional implications of the studied variants.Results: A significant increase in TEX15-rs1362912 minor allele frequency (MAF) was observed in the group of SO patients (MAF = 0.0842) compared to either the control cohort (MAF = 0.0468, OR = 1.90, p = 7.47E-03) or the NOA group (MAF = 0.0472, OR = 1.83, p = 1.23E-02). The genotype distribution of the SO population was also different from those of both control (p = 1.14E-02) and NOA groups (p = 4.33–02). The analysis of functional annotations of the human genome suggested that the effect of the SO-associated TEX15 variants is likely exerted by alteration of the binding affinity of crucial transcription factors for spermatogenesis.Conclusion: Our results suggest that common variation in TEX15 is involved in the genetic predisposition to SO, thus supporting the notion of idiopathic SPGF as a complex trait.

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