| HRA000976
(Controlled Access)
|
Type 2 diabetes mellitus is one of the most prevalent metabolic diseases affecting multiple organs, including reproductive disorders in male diabetic patients. Here, we performed smart-seq2 to examine the transcriptome of diabetic patients' testis cells at single cell resolution. Intriguingly, whereas spermatogenesis appears largely preserved, the gene expression profiles of Sertoli cells and the blood-testis barrier (BTB) structure were dramatically impaired. Among the deregulated pathways, the Apelin (APLN) peptide /Apelin-receptor (APJ) axis was hyper-activated in diabetic patients. Together, these effects culminated in BTB structural dysfunction. Finally, using the small molecule APLN receptor antagonist, ML221, we show that blocking APLN/APJ significantly ameliorated the BTB damage and, importantly, improved functional spermatogenesis in diabetic db/db micse. Our findings identify the APLN/APJ axis as a promising therapeutic target to improve reproduction capacity in male diabetic patients. |
