Lisbon clinical group co-authors and
IVIRMA group co-authors
Ana Aguiar, (Unidade de Medicina da Reproducao,
Hospital de Santa Maria, Centro Hospitalar Lisboa Norte,
Lisboa, Portugal); Carlos Calhaz-Jorge, (Unidade de Medicina
da Reproducao, Hospital de Santa Maria, Centro Hospitalar
Lisboa Norte, Lisboa, Portugal); Joaquim Nunes, (Unidade de
Medicina da Reproducao, Hospital de Santa Maria, Centro
Hospitalar Lisboa Norte, Lisboa, Portugal); Sandra Sousa
(Unidade de Medicina da Reproducao, Hospital de Santa
Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal),
and Sónia Correia (Centro de Medicina Reprodutiva,
Maternidade Alfredo da Costa, Centro Hospitalar Lisboa
Central, Lisboa, Portugal); Maria Graça Pinto(Centro de
Medicina Reprodutiva, Maternidade Alfredo da Costa,
Centro Hospitalar Lisboa Central, Lisboa, Portugal).
Alberto Pacheco, (IVIRMA Madrid, Spain); Cristina
González, (IVIRMA Sevilla, Spain); Susana Gómez,
(IVIRMA Lisboa, Portugal); David Amorós, (IVIRMA
Barcelona, Spain); Jesús Aguilar, (IVIRMA Vigo, Spain);
Fernando Quintana, (IVIRMA Bilbao, Spain).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.This work was supported by the Spanish Ministry of
Science and Innovation through the Spanish National Plan
for Scientific and Technical Research and Innovation (PID
2020-120157RB-I00) and the Andalusian Government
through the research projects of “Plan Andaluz de
Investigacion, Desarrollo e Innovacion (PAIDI 2020)” (ref.
PY20_00212) and “Programa Operativo FEDER 2020” (ref.
B-CTS-584-UGR20). LB-C was supported by the Spanish
Ministry of Science and Innovation through the “Juan de la
Cierva Incorporacion” program (Grant ref. IJC 2018-038026-
I, funded by MCIN/AEI/10.13039/501100011033), which
includes FEDER funds. AG-J was funded by MCIN/AEI/
10.13039/501100011033 and FSE “El FSE invierte en tu
futuro” (grant ref. FPU20/02926). IPATIMUP integrates
the i3S Research Unit, which is partially supported by the
Portuguese Foundation for Science and Technology (FCT),
financed by the European Social Funds (COMPETE-FEDER)
and National Funds (projects PEstC/SAU/LA0003/2013 and
POCI-01-0145-FEDER-007274). PM is supported by the FCT
post-doctoral fellowship (SFRH/BPD/120777/2016), financed
from the Portuguese State Budget of the Ministry for Science, Technology and High Education and from the European
Social Fund, available through the Programa Operacional
do Capital Humano. ToxOmics—Centre for
Toxicogenomics and Human Health, Genetics, Oncology
and Human Toxicology, Nova Medical School, Lisbon, is
also partially supported by FCT (UID/BIM/00009/2016 and
UIDB/00009/2020). SL received support from Instituto de
Salud Carlos III (grant: DTS18/00101], co-funded by
FEDER funds/European Regional Development Fund
(ERDF)-a way to build Europe-), and from “Generalitat de
Catalunya” (grant 2017SGR191). SL is sponsored by the
“Researchers Consolidation Program” from the SNS-Dpt.
Salut Generalitat de Catalunya (Exp. CES09/020). This
article is related to the Ph.D. Doctoral Thesis of AG-J.info:eu-repo/semantics/publishedVersio
