TXNDC2 joint molecular marker is associated with testis pathology and is an accurate predictor of sperm retrieval

Seyed-Morteza Javadirad,Mohammad Mokhtari

doi:10.1038/s41598-021-92603-3

Seyed-Morteza Javadirad, Mohammad Mokhtari

Open Access

https://doi.org/10.1038/s41598-021-92603-3

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Abstract

The association of PRM1/2 with male azoospermia is well-documented, but the relationship between TXNDC2 deficiency and the azoospermia phenotype, sperm retrieval, and pathology has not been elucidated. Here we identified the association of TXNDC2 and protamines in evaluating testis pathology and sperm retrieval. An extensive microarray meta-analysis of men with idiopathic azoospermia was performed, and after undergoing several steps of data quality controls, the data passing QC were pooled and batch effect corrected. As redox imbalance has been shown to have a variable relationship with fertility, our relative expression studies began with candidate protamination and thioredoxin genes. We constructed a logistic regression model of TXNDC2 with PRM1 and PRM2 genes, and collective ROC analysis indicated a sensitivity of 96.8% and specificity of 95.5% with a ROC value of 0.995 (SE = 0.0070, 95% CI 0.982–1.000). These results demonstrate that TXNDC2, PRM1, and PRM2 combined have a robust power to predict sperm retrieval and correlate with severe azoospermia pathology.

Highlights

The association of PRM1/2 with male azoospermia is well-documented, but the relationship between TXNDC2 deficiency and the azoospermia phenotype, sperm retrieval, and pathology has not been elucidated
Aberrant spermatogenesis is classified into five main pathologic patterns[1]: seminiferous tubule hyalinization (SH), Sertoli cell-only syndrome (SCOS), early maturation arrest, late maturation arrest, and hypospermatogenesis (Hypo)
The second round of quality control was carried out to assess the quality of sample quantiles (Supplementary Fig. 1)

Summary

Introduction

The association of PRM1/2 with male azoospermia is well-documented, but the relationship between TXNDC2 deficiency and the azoospermia phenotype, sperm retrieval, and pathology has not been elucidated. We identified the association of TXNDC2 and protamines in evaluating testis pathology and sperm retrieval. We constructed a logistic regression model of TXNDC2 with PRM1 and PRM2 genes, and collective ROC analysis indicated a sensitivity of 96.8% and specificity of 95.5% with a ROC value of 0.995 (SE = 0.0070, 95% CI 0.982–1.000). These results demonstrate that TXNDC2, PRM1, and PRM2 combined have a robust power to predict sperm retrieval and correlate with severe azoospermia pathology. The aim of this study was to evaluate the expression levels of TXNDC2 concomitantly with protamination genes in different azoospermia pathologies. Logistic regression model analysis of combined TXNDC2, PRM1, and PRM2 genes was a robust predictor of SR, providing a sensitivity of 96.8% and specificity of 95.5%

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