Distributed Algorithms for Target Localization in Wireless Sensor Networks Using Hybrid Measurements

This dissertation addresses the target localization problem in wireless sensor networks (WSNs). WSNs is now a widely applicable technology which can have numerous practical applications and offer the possibility to improve people’s lives. A required feature to many functions of a WSN, is the ability to indicate where the data reported by each sensor was measured. For this reason, locating each sensor node in a WSN is an essential issue that should be considered. In this dissertation, a performance analysis of two recently proposed distributed localization algorithms for cooperative 3-D wireless sensor networks (WSNs) is presented. The tested algorithms rely on distance and angle measurements obtained from received signal strength (RSS) and angle-of-arrival (AoA) information, respectively. The measurements are then used to derive a convex estimator, based on second-order cone programming (SOCP) relaxation techniques, and a non-convex one that can be formulated as a generalized trust region sub-problem (GTRS). Both estimators have shown excellent performance assuming a static network scenario, giving accurate location estimates in addition to converging in few iterations. The results obtained in this dissertation confirm the novel algorithms’ performance and accuracy. Additionally, a change to the algorithms is proposed, allowing the study of a more realistic and challenging scenario where different probabilities of communication failure between neighbor nodes at the broadcast phase are considered. Computational simulations performed in the scope of this dissertation, show that the algorithms’ performance holds for high probability of communication failure and that convergence is still achieved in a reasonable number of iterations

Evaluation of the potential association of SOHLH2 polymorphisms with non-obstructive azoospermia susceptibility in a large European population

Non-obstructive azoospermia (NOA) or spermatogenic failure is a complex disease with an important genetic component that causes infertility in men. Known genetic factors associated with NOA include AZF microdeletions of the Y chromosome or karyotype abnormalities; however, most causes of NOA are idiopathic. During the last decade, a large list of associations between single-nucleotide polymorphisms (SNP) and NOA have been reported. However, most of the genetic studies have been performed only in Asian populations. We aimed to evaluate whether the previously described association in Han Chinese between NOA and two SNPs of the SOHLH2 gene (involved in the spermatogenesis process) may also confer risk for NOA in a population of European ancestry. We genotyped a total of 551 NOA patients (218 from Portugal and 333 from Spain) and 1,050 fertile controls (226 from Portugal and 824 from Spain) for the genetic variants rs1328626 and rs6563386 using TaqMan assays. To test for association, we compared the allele and genotype frequencies between cases and controls using an additive model. A haplotype analysis and a meta-analysis using the inverse variance method with our data and those of the original Asian study were also performed. No statistically significant differences were observed in any of the analyses described above. Therefore, considering the high statistical power of our study, it is not likely that the two analysed SOHLH2 genetic variants are related with an increase susceptibility to NOA in the European population.info:eu-repo/semantics/publishedVersio

Common genetic variation in KATNAL1 non-coding regions is involved in the susceptibility to severe phenotypes of male infertility

Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546047/Background: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure. Objectives: The main objective of the present study is to evaluate the effect of the common genetic variation of KATNAL1 in a large and phenotypically well-characterised cohort of infertile men because of severe spermatogenic failure. Materials and methods: A total of 715 infertile men because of severe spermato genic failure, including 210 severe oligospermia and 505 non-obstructive azoospermia patients, as well as 1058 unaffected controls were genotyped for three KATNAL1 single-nucleotide polymorphism taggers (rs2077011, rs7338931 and rs2149971). Case–control association analyses by logistic regression assuming different models and in silico functional characterisation of risk variants were conducted. Results: Genetic associations were observed between the three analysed taggers and different severe spermatogenic failure groups. However, in all cases, the haplotype model (rs2077011*C | rs7338931*T | rs2149971*A) better explained the observed associations than the three risk alleles independently. This haplotype was associated with non-obstructive azoospermia (adjusted p = 4.96E-02, odds ratio = 2.97), Sertoli cell only syndrome (adjusted p = 2.83E-02, odds ratio = 5.16) and testicular sperm extraction unsuccessful outcomes (adjusted p = 8.99E-04, odds ratio = 6.13). The in silico analyses indicated that the effect on severe spermatogenic failure predisposition could be because of an alteration of the KATNAL1 splicing pattern. Conclusions: Specific allelic combinations of KATNAL1 genetic polymorphisms may confer a risk of developing severe male infertility phenotypes by favouring the overrepresentation of a short non-functional transcript isoform in the testis.This work was supported by the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (refs. SAF2016-78722-R and PID2020-120157RB-I00), the ‘Instituto de Salud Carlos III’ (Fondo de Investigaciones Sanitarias)/Fondo Europeo de Desarrollo Regional ‘Una manera de hacer Europa’ (FIS/FEDER) (ref. DTS18/00101 to Sara Larriba), the Generalitat de Catalunya (ref. 2017SGR191), the ‘Ramón y Cajal’ program (ref. RYC-2014-16458) and the ‘Juan de la Cierva Incorporación’ program (ref. IJC2018-038026-I), as well as the Andalusian Government through the R&D&i Projects Grants for Universities and Public Research Entities (ref. PY20_00212), which include FEDER funds. Andrea Guzmán-Jiménez was a recipient of a grant from the Spanish Ministry of Education and Professional Training (‘Becas de Colaboración en Departamentos Universitarios para el curso académico 2020/2021’). Patricia I. Marques is supported by the FCT post-doctoral fellowship (SFRH/BPD/120777/2016), financed from the Portuguese State Budget of the Ministry for Science, Tech nology and High Education and from the European Social Fund, available through the ‘Programa Operacional do Capital Humano’. João Gonçalves was partially funded by FCT/MCTES through national funds attributed to the Centre for Toxicogenomics and Human Health— ToxOmics (UID/BIM/00009/2016 and UIDB/00009/2020). Sara Larriba is sponsored by the Researchers Consolidation Program (ISCIII SNS/Dpt. Salut Generalitat de Catalunya) (CES09/020).info:eu-repo/semantics/publishedVersio

Common genetic variation in KATNAL1 non‐coding regions is involved in the susceptibility to severe phenotypes of male infertility

© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Background: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single-nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure. Objectives: The main objective of the present study is to evaluate the effect of the common genetic variation of KATNAL1 in a large and phenotypically well-characterised cohort of infertile men because of severe spermatogenic failure. Materials and methods: A total of 715 infertile men because of severe spermatogenic failure, including 210 severe oligospermia and 505 non-obstructive azoospermia patients, as well as 1058 unaffected controls were genotyped for three KATNAL1 single-nucleotide polymorphism taggers (rs2077011, rs7338931 and rs2149971). Case-control association analyses by logistic regression assuming different models and in silico functional characterisation of risk variants were conducted. Results: Genetic associations were observed between the three analysed taggers and different severe spermatogenic failure groups. However, in all cases, the haplotype model (rs2077011*C | rs7338931*T | rs2149971*A) better explained the observed associations than the three risk alleles independently. This haplotype was associated with non-obstructive azoospermia (adjusted p = 4.96E-02, odds ratio = 2.97), Sertoli-cell only syndrome (adjusted p = 2.83E-02, odds ratio = 5.16) and testicular sperm extraction unsuccessful outcomes (adjusted p = 8.99E-04, odds ratio = 6.13). The in silico analyses indicated that the effect on severe spermatogenic failure predisposition could be because of an alteration of the KATNAL1 splicing pattern. Conclusions: Specific allelic combinations of KATNAL1 genetic polymorphisms may confer a risk of developing severe male infertility phenotypes by favouring the overrepresentation of a short non-functional transcript isoform in the testis.This work was supported by the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (refs. SAF2016-78722-R and PID2020-120157RB-I00), the ‘Instituto de Salud Carlos III’ (Fondo de Investigaciones Sanitarias)/Fondo Europeo de Desarrollo Regional ‘Una manera de hacer Europa’ (FIS/FEDER) (ref. DTS18/00101 to Sara Larriba), the Generalitat de Catalunya (ref. 2017SGR191), the ‘Ramón y Cajal’ program (ref. RYC-2014-16458) and the ‘Juan de la Cierva Incorporación’ program (ref. IJC2018-038026-I), as well as the Andalusian Government through the R&D&i Projects Grants for Universities and Public Research Entities (ref. PY20_00212), which include FEDER funds. Andrea Guzmán-Jiménez was a recipient of a grant from the Spanish Ministry of Education and Professional Training (‘Becas de Colaboración en Departamentos Universitarios para el curso académico 2020/2021’). Patricia I. Marques 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’. João Gonçalves was partially funded by FCT/MCTES through national funds attributed to the Centre for Toxicogenomics and Human Health—ToxOmics (UID/BIM/00009/2016 and UIDB/00009/2020). Sara Larriba is sponsored by the Researchers Consolidation Program (ISCIII SNS/Dpt. Salut Generalitat de Catalunya) (CES09/020).info:eu-repo/semantics/publishedVersio

Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome

Funding Information: Funding: This work was supported by the Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020) (ref. PY20_00212, P20_00583), and the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (ref. SAF2016–78722-R, PID2020–120157RB-I00) and the Proyectos I + D + i del Programa Operativo FEDER 2020 (ref. B-CTS-584-UGR20, B-CTS-260-UGR20). FDC was supported by the “Ramón y Cajal” program (ref. RYC-2014–16458), and LBC was supported by the Spanish Ministry of Economy and Competitiveness through the “Juan de la Cierva Incorporación” program (Grant ref. IJC2018– 038026-I, funded by MCIN/AEI/10.13039/501100011033), all of them including FEDER funds. AGJ was funded by MCIN/AEI/10.13039/501100011033 and FSE “El FSE invierte en tu futuro”(grant ref. FPU20/02926). SGM was funded by a previously mentioned project (ref. PY20_00212). 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). AML is funded by the Portuguese Government through FCT (IF/01262/2014). PIM 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 (Projects: UID/BIM/00009/2013 and UIDB/UIDP/00009/2020). SLarriba 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). SLarriba 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 Miriam Cerván-Martín (grant ref. BES-2017–081222 funded by MCIN/AEI/10.13039/501100011033 and FSE “El FSE invierte en tu futuro”). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.We aimed to analyze the role of the common genetic variants located in the PIN1 locus, a relevant prolyl isomerase required to control the proliferation of spermatogonial stem cells and the integrity of the blood–testis barrier, in the genetic risk of developing male infertility due to a severe spermatogenic failure (SPGF). Genotyping was performed using TaqMan genotyping assays for three PIN1 taggers (rs2287839, rs2233678 and rs62105751). The study cohort included 715 males diagnosed with SPGF and classified as suffering from non-obstructive azoospermia (NOA, n = 505) or severe oligospermia (SO, n = 210), and 1058 controls from the Iberian Peninsula. The allelic frequency differences between cases and controls were analyzed by the means of logistic regression models. A subtype specific genetic association with the subset of NOA patients classified as suffering from the Sertoli cell-only (SCO) syndrome was observed with the minor alleles showing strong risk effects for this subset (ORaddrs2287839 = 1.85 (1.17–2.93), ORaddrs2233678 = 1.62 (1.11–2.36), ORaddrs62105751 = 1.43 (1.06–1.93)). The causal variants were predicted to affect the binding of key transcription factors and to produce an altered PIN1 gene expression and isoform balance. In conclusion, common non-coding single-nucleotide polymorphisms located in PIN1 increase the genetic risk to develop SCO.publishersversionpublishe

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

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

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

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

Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility

We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DR beta 1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition. A GWAS in a large case-control cohort of European ancestry identifies two genomic regions, the MHC class II gene HLA-DRB1 and an upstream locus of VRK1, that are associated with the most severe phenotype of spermatogenic failure

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

Funding: This work was supported by the Spanish Ministry of Economy and Competitiveness through the Spanish State Plan for Scientific and Technical Research and Innovation (ref. SAF2016-78722-R), the “Ramón y Cajal” program (ref. RYC-2014-16458), and the “Juan de la Cierva Incorporación” program (ref. IJC2018-038026-I), which include FEDER funds. SLa received support from the Spanish Ministry of Science and Innovation (grants FIS-ISCIII DTS18/00101, co-funded by FEDER funds/European Regional Development Fund (ERDF)-a way to build Europe-), and from Generalitat de Catalunya (grant 2017SGR191). AG-J was recipient of a grant from the “Plan Propio” program of the University of Granada (“Becas de Iniciación a la Investigación para estudiantes de Grado”, conv.2019). SLa is sponsored by the “Researchers Consolidation Program” from the SNS-Dpt. Salut Generalitat de Catalunya (Exp. CES09/020). JG was partially funded by FCT/MCTES, through national funds attributed to Center for Toxicogenomics and Human Health—ToxOmics (UIDB/00009/2020). PIM 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. AML is funded by the Portuguese Government through FCT (IF/01262/2014). IPATIMUP integrates the i3S Research Unit, which is partially supported by 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.publishersversionpublishe