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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.

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