Txndc2, a thioredoxin domain-containing protein, is involved in regulating the redox status. Thioredoxins play crucial roles in antioxidant defense systems, and Txndc2 may contribute to maintaining the appropriate redox balance within cells, which is essential for normal cellular function and survival. It may be associated with pathways related to spermatogenesis and oxidative stress response [2].

Functionally deleting Txndc2 (along with Txndc3) in the male germ line of mice did not impact spermatogenesis, epididymal sperm maturation, or fertility overall. However, it led to age-dependent changes in spermatozoa, such as accelerated motility loss, high rates of DNA damage, increased reactive oxygen species generation, enhanced formation of lipid aldehyde-protein adducts, and impaired protamination of the sperm chromatin [2].

In humans, a homozygous deletion in TXNDC2 was identified in azoospermia patients from consanguineous Pakistani families, suggesting its potential pathogenic relevance to male infertility [4]. Also, combined analysis of TXNDC2 with PRM1 and PRM2 genes showed a high sensitivity (96.8%) and specificity (95.5%) in predicting sperm retrieval and correlating with severe azoospermia pathology [1]. In addition, in cattle-yak with male-derived sterility, the expression of TXNDC2 was significantly downregulated compared to yak [3].

In conclusion, Txndc2 is critically important in protecting spermatozoa against age-related oxidative stress. Its deletion in mouse models reveals its role in maintaining sperm function. In humans, its genetic variants are associated with azoospermia, highlighting its significance in male infertility research. The study of Txndc2 using gene-knockout models helps to understand the molecular mechanisms underlying male infertility and provides insights for potential diagnostic and therapeutic approaches.