Identification of ferroptotic genes and phenotypes in idiopathic nonobstructive azoospermia.
Syst Biol Reprod Med
; 69(6): 410-422, 2023 Dec.
Article
en En
| MEDLINE
| ID: mdl-37782778
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Azoospermia
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
Syst Biol Reprod Med
Asunto de la revista:
MEDICINA REPRODUTIVA
/
UROLOGIA
Año:
2023
Tipo del documento:
Article
Pais de publicación:
Reino Unido