Study on the Correlation of Collagen Receptor DDR2 with Non-obstructive Azoospermia
Objective To investigate the correlation between collagen receptor DDR2 and non-obstructive azoospermia(NO A)and to clarify the localization of its expression in the testis.Methods Testicular tissue chip data(GSE45885)of NOA patients from GEO database were obtained,and the expression changes and correlation of DDR2 among four different severities of NOA were detected by limma differential gene analysis and WGCNA analysis.By analyzing the single-cell transcriptome sequencing data of testicular tissues,the expression localization of DDR2,the pseudo-temporal dynamic changes and the communication relationship between the target cells were clarified.Finally,a DDR2-/-mice model was used to validate the regulatory role of DDR2 on spermatogenesis.Results DDR2 was closely associated with the development of severe NOA,and its expression level increased with the worsening of azoospermia,with the highest level in patients with sertoli cell-only syndrome(SCOS)(P＜0.001),followed by meiotic arrest,meiotic arrest,and post-meiotic arrest.DDR2 was highly expressed in testicular leydig cells(LCs)and peritubular myoid cells(PMCs),with expression levels consistent with the marker genes Cyp17a1,Myh11,and Sbspon in the pseudo-temporal order of fibroblast-derived cells,and was overexpressed in mid-and late-stage differentiated cells,and underexpressed in pre-differentiated cells.Analysis of cellular communication revealed that DDR2 might be involved in regulating intercellular communication between LCs and PMCs through the ligand-receptor of Col1a1_Col1a2-Itga9_Itgb1/Sdc4.DDR2-/-male mice exhibited severe spermatogenesis disorders,with significant reductions in sperm viability,total sperm motility,and effective sperm counts.Conclusion DDR2 was closely related to the pathogenesis of severe NOA,and may affect spermatogenesis by participating in the communication between LCs and PMCs.
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