Identification of ferroptotic genes and phenotypes in idiopathic nonobstructive azoospermia

Abstract

Effective treatments for nonobstructive azoospermia (NOA), which affects 1% of all men globally, are limited by undefined pathogenic mechanisms, especially in idiopathic NOA (iNOA). Here, we tried to identify the functional ferroptosis-related genes and phenotypes involved in iNOA. Differentially expressed ferroptotic genes were identified from iNOA mRNA microarray datasets by bioinformatic analyses, and these ferroptotic genes were subsequently filtered by various algorithms. Then, receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic ability of the abovementioned genes for iNOA. Generally, 11 differentially expressed ferroptotic genes were downregulated, and five genes were upregulated in iNOA samples. Four genes, including DUSP1, GPX4, HSD17B11, and SLC2A8, were technically selected and determined to be potential biomarkers for iNOA. Subsequently, similar expression levels were validated at both the RNA and protein levels in the iNOA specimens. Finally, morphologic and biochemical assays were applied to define the ferroptotic phenotypes in testes. The ferroptotic features, like shrunken mitochondria with electron-dense membranes and a reduction in cristae were observed across various cell types within iNOA patients, accompanied by the overload of ferrous ions and increased lipid peroxidation production. Our findings demonstrated that these ferroptosis genes could be involved in the underlying pathogenesis mechanisms of iNOA by regulating ferroptosis and serve as potential diagnostic biomarkers. Also, the ferroptotic phenotypes were identified in iNOA patients.

Keywords:

• Ferroptosis
• iNOA
• bioinformatic analysis
• differential expressed genes

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors contributions

Conception and design: GA, CL; Bioinformatic analysis: TP, CL, XL; Performed the experiments: CL, XL; Drafted the manuscript: CL, TP, ZC; Collected all samples: MW, XY, YL, XF.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. The public datasets can be obtained from the GEO website (https://www.ncbi.nlm.nih.gov/geo/).

Additional information

Funding

This work was supported by the National Key R&D Plan under Grant no. 2019YFE0109500; the National Natural Science Foundation of China under Grant no. 82171589; the Guangdong Natural Science Foundation under Grant no. 2019A1515011439; and the Science and Technology Program of Guangzhou, China under Grant no.202102010075.