ESX1 mRNA expression in seminal fluid is an indicator of residual spermatogenesis in non-obstructive azoospermic men

Pansa, Alessandra; Sirchia, Silvia Maria; Melis, Sara; Giacchetta, Daniela; Castiglioni, Massimo; Colapietro, Patrizia; Fiori, Stefano; Falcone, Rossella; Paganini, Leda; Bonaparte, Eleonora; Colpi, Giovanni M.; Miozzo, Monica; Tabano, Silvia

doi:10.1093/humrep/deu261

Cited by 28 publications

(28 citation statements)

References 24 publications

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“…The prediction of sperm retrieval by TEX101 was comparable to other biomarkers that predict sperm retrieval, including seminal protein LGALS3BP (AUC = 0.76; 100% sensitivity at 45% specificity) [39], seminal leptin (AUC = 0.59; 43% sensitivity at 75% specificity) [40], seminal ESX1 mRNA (84% sensitivity at 28% specificity) [41], and blood serum FSH protein (AUC = 0.62; 71% sensitivity at 68% specificity) [40]. Better biomarkers to predict sperm retrieval in NOA patients are still required.…”

Section: Discussionmentioning

confidence: 80%

Preclinical evaluation of a TEX101 protein ELISA test for the differential diagnosis of male infertility

Korbakis

Schiza

Brinc

et al. 2017

BMC Med

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BackgroundTEX101 is a cell membrane protein exclusively expressed by testicular germ cells and shed into seminal plasma. We previously verified human TEX101 as a biomarker for the differential diagnosis of azoospermia, and developed a first-of-its-kind TEX101 ELISA. To demonstrate the clinical utility of TEX101, in this work we aimed at evaluating ELISA performance in a large population of fertile, subfertile, and infertile men.MethodsMass spectrometry, size-exclusion chromatography, ultracentrifugation, and immunohistochemistry were used to characterize TEX101 protein as an analyte in seminal plasma. Using the optimized protocol for seminal plasma pretreatment, TEX101 was measured by ELISA in 805 seminal plasma samples.ResultsWe demonstrated that TEX101 was present in seminal plasma mostly in a free soluble form and that its small fraction was associated with seminal microvesicles. TEX101 median values were estimated in healthy, fertile pre-vasectomy men (5436 ng/mL, N = 64) and in patients with unexplained infertility (4967 ng/mL, N = 277), oligospermia (450 ng/mL, N = 270), and azoospermia (0.5 ng/mL, N = 137). Fertile post-vasectomy men (N = 57) and patients with Sertoli cell-only syndrome (N = 13) and obstructive azoospermia (N = 36) had undetectable levels of TEX101 (≤0.5 ng/mL). A cut-off value of 0.9 ng/mL provided 100% sensitivity at 100% specificity for distinguishing pre- and post-vasectomy men. The combination of a concentration of TEX101 > 0.9 ng/mL and epididymis-specific protein ECM1 > 2.3 μg/mL provided 81% sensitivity at 100% specificity for differentiating between non-obstructive and obstructive azoospermia, thus eliminating the majority of diagnostic testicular biopsies. In addition, a cut-off value of ≥0.6 ng/mL provided 73% sensitivity at 64% specificity for predicting sperm or spermatid retrieval in patients with non-obstructive azoospermia.ConclusionsWe demonstrated the clinical utility of TEX101 ELISA as a test to evaluate vasectomy success, to stratify azoospermia forms, and to better select patients for sperm retrieval.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0817-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 80%

Preclinical evaluation of a TEX101 protein ELISA test for the differential diagnosis of male infertility

Korbakis

Schiza

Brinc

et al. 2017

BMC Med

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“…Different studies recently identified seminal proteins including ECM1, TEX101 (Drabovich et al, 2013;Rolland et al, 2012) or trace RNA including DDX4, SEMG1, TGM4 and ESXI (H. Li, Wu, Gu, & Xiong, 2012;Pansa et al, 2014). We also studied the relative expression of ESX1, ZMYND15, SPEM1, TNP1 and PRM1 mRNA in testicular biopsies of individuals with NOA, and we concluded the post-meiotic markers were more suitable for prediction of successful sperm retrieval following mTESE (Hashemi et al, 2018a(Hashemi et al, , 2018b.…”

Section: Discussionmentioning

confidence: 81%

Could analysis of testis‐specific genes, as biomarkers in seminal plasma, predict presence of focal spermatogenesis in non‐obstructive azoospermia?

et al. 2019

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Cell-free seminal mRNA (cfs-mRNA) exists in the human ejaculate that is proposed as a potential noninvasive procedure to prognosis pathophysiological conditions. This study applied cfs-mRNA of ESX1, ZMYND15 and its target haploid genes (TNP1 and PRM1) to identify the presence of spermatozoa in men with azoospermia. This study included 35 semen samples from 16 normozoospermic and 19 nonobstructive azoospermic individuals. Expression levels of target genes were determined by real-time reverse transcription-polymerase chain reaction using ΔΔCt method. The expression level of these genes (ZMYND15, TNP1 and PRM1) was significantly decreased in semen samples of nonobstructive azoospermia compared to normozoospermia.Similarly, the expression level of TNP1 and PRM1 was significantly decreased in the sample with negative sperm (SR−) versus positive sperm retrieval (SR+). The expression level of these genes may have the potential for prediction of successful sperm retrieval with high sensitivity and specificity according to the receiver operating characteristics (ROC) curve analysis. K E Y W O R D Sazoospermia, male infertility, seminal plasma, sperm retrieval

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“…Some molecular markers have previously been proposed; for example, ESX1 was identified in 95.4% of studied cases and showed a specificity of 74% and sensitivity of 80% for predicting residual spermatogenesis [29]. In a study by Ando et al [22], the level of VASA transcription was evaluated using RT-qPCR in 52 samples from men with NOA, and it was demonstrated to be a predictive factor for sperm recovery, with 86.2% specificity and 87.0% sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of the RNF8 gene can predict the presence of sperm in azoospermic individuals

Nazari

Babakhanzadeh

Zarch

et al. 2020

Clin Exp Reprod Med

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Objective: In this study, specimens from testicular biopsies of men with nonobstructive azoospermia (NOA) were used to investigate whether RNF8 gene could serve as a biomarker to predict the presence of sperm in these patients. Methods: Testicular biopsy specimens from 47 patients were classified according to the presence of sperm (positive vs. negative groups) and investigated for the expression of RNF8. The level of RNF8 gene expression in the testes was compared between these groups using reversetranscription polymerase chain reaction. Results: The expression level of RNF8 was significantly higher in testicular samples from the positive group than in those from the negative group. Moreover, the area under the curve of RNF8 expression for the entire study population was 0.84, showing the discriminatory power of RNF8 expression in differentiating between the positive and negative groups of men with NOA. A receiver operating characteristic curve analysis showed that RNF8 expression had a sensitivity of 81% and a specificity of 84%, with a cutoff level of 1.76. Conclusion: This study points out a significant association between the expression of RNF8 and the presence of sperm in NOA patients, which suggests that quantified RNF8 expression in testicular biopsy samples may be a valuable biomarker for predicting the presence of spermatozoa in biopsy samples. This is an Open Access article distributed under the terms of the Creative Commons AttributionNon-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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ESX1 mRNA expression in seminal fluid is an indicator of residual spermatogenesis in non-obstructive azoospermic men

Abstract: This work was supported by the Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: Ricerca Corrente [grant number RC2014/519-02] to M.M. and from ASM onlus 2010-2011 to M.M. The authors declare that they have no conflict of interest.

Cited by 28 publications

References 24 publications

Preclinical evaluation of a TEX101 protein ELISA test for the differential diagnosis of male infertility

Preclinical evaluation of a TEX101 protein ELISA test for the differential diagnosis of male infertility

Could analysis of testis‐specific genes, as biomarkers in seminal plasma, predict presence of focal spermatogenesis in non‐obstructive azoospermia?

Upregulation of the RNF8 gene can predict the presence of sperm in azoospermic individuals

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