Abstract
BackgroundLoss of functional allele for discoidin domain receptor 2 (Ddr2) results in impaired Leydig cell response to luteinizing hormone (LH), low testosterone production and arrested spermatogenesis in older male Ddr2slie/slie mice. However, the underlying mechanism responsible for this phenotype remains unknown. Herein, we reported for the first time that the deregulated expression of Ddr2 cognate ligand, namely collagen type I (COL1), may account for the disruption of the testicular steroidogenesis in Ddr2slie/slie mutant testes.Methodology/Principal FindingsExpression of Ddr2 increased gradually along postnatal development, whereas COL1 expression became negligible from adulthood onwards. In Ddr2slie/slie mutant testis, however, in contrast to the undetectable staining of Ddr2, COL1 expression was constantly detected, with the highest values detected during adulthood. In the experimental vasectomy model, Ddr2slie/slie mutant mice exhibited an early androgen deficiency than wild-type mice, along with the accumulation of fibrotic tissue in the interstitium. Functionally, ablation of endogenous Ddr2 resulted in a significant decrease of testosterone (T) level in TM3 cells in the presence of higher concentration of COL1 treatment. Conversely, overexpression of Ddr2 could help TM3 cells to maintain a normal testicular steroidogenesis even in the presence of high concentration of COL1. Additionally, attenuated expression of Ddr2 correlates to the deregulated level of serum T levels in human pathological testes.ConclusionsAbnormal accumulation of interstitial COL1 may be responsible for the steroidogenic dysfunction in Ddr2slie/slie mutant testes.
Highlights
The discoidin domain receptor superfamily, belonging to the receptor tyrosine kinase (RTK) family, mainly consists of DDR1 and DDR2
Abnormal accumulation of interstitial COL1 may be responsible for the steroidogenic dysfunction in Ddr2slie/slie mutant testes
Apparent that DDR2 expression were stimulated by relatively low concentration of COL1 (24 μg/cm2), and was significantly inhibited by highest concentration of COL1 (96 μg/cm2) in TM3 cells after 24 hours of incubation (Fig 2)
Summary
The discoidin domain receptor superfamily, belonging to the receptor tyrosine kinase (RTK) family, mainly consists of DDR1 and DDR2. Their activations require binding by differential collagens [1]. Several intrinsic characteristics make DDRs different from other RTKs. In stead of growth factors, activation of DDRs requires collagens binding. In stead of growth factors, activation of DDRs requires collagens binding This activation occurs and maintains within a longer time window [2]. We reported for the first time that the deregulated expression of Ddr cognate ligand, namely collagen type I (COL1), may account for the disruption of the testicular steroidogenesis in Ddr2slie/slie mutant testes
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.