Discoidin Domain Receptor 2 (DDR2) Is Required for Maintenance of Spermatogenesis in Male Mice

Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase (RTK). We recently identified homozygous smallie mutant mice (BKS.HRS. Ddr2(slie/slie)/J, Ddr2(slie/slie) mutants), which lack a functional DDR2. Ddr2(slie/slie) mutant mice are dwarfed and infertile due to peripheral dysregulation of the endocrine system. To understand the role of DDR2 signaling in spermatogenesis, we studied the expression of several receptors, enzymes, and proteins related to spermatogenesis in wild-type and Ddr2(slie/slie) mutant mice at 10 weeks and 5 months of age. DDR2 were expressed in adult wild-type male mice in Leydig cells. The number of differentiated spermatozoa in the seminal fluid was significantly lower in the Ddr2(slie/slie) mutant mice than in the wild-type mice. The number of TUNEL-positive cells was significantly greater in 5-month-old Ddr2(slie/slie) mutants. Testosterone was significantly reduced at 5 months age, but LH was similar in both types of mice at both 10 weeks and 5 months of age. The expression levels of LH receptors (Lhcgr), StAR, P450scc, and Hsd3 beta 6 were significantly different between the two types of mice at 10 weeks of age, but they were significantly reduced in 5-month-old Ddr2(slie/slie) mutants compared to wild-type mice of the same age. DDR2 was expressed in the Leydig cells of adult wild-type male mice. In conclusion, our results indicated that DDR2 signaling plays a critical role in the maintenance of male spermatogenesis.