Related Experiment Video
Updated: Apr 7, 2026
Optical Sectioning and Visualization of the Intervertebral Disc from Embryonic Development to Degeneration
Published on: July 8, 2021
Abnormal Accumulation of Collagen Type I Due to the Loss of Discoidin Domain Receptor 2 (Ddr2) Promotes Testicular
Chu-chao Zhu1, Bin Tang2, Jin Su3
1Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi'an 710032, China.
Background:
Loss 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 Findings:
Expression 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.
Conclusions:
Abnormal accumulation of interstitial COL1 may be responsible for the steroidogenic dysfunction in Ddr2slie/slie mutant testes.
Insights
Loss of discoidin domain receptor 2 (Ddr2) impairs Leydig cell function and testosterone production. Abnormal collagen type I (COL1) accumulation disrupts testicular steroidogenesis in Ddr2 mutant mice.
Area of Science:
- Reproductive biology
- Molecular endocrinology
- Cell biology
Background:
- Loss of functional discoidin domain receptor 2 (Ddr2) allele impairs Leydig cell response to luteinizing hormone (LH), leading to low testosterone and arrested spermatogenesis in Ddr2slie/slie mice.
- The precise mechanism underlying this phenotype remains unclear.
- This study investigates the role of Ddr2's ligand, collagen type I (COL1), in testicular steroidogenesis disruption.
Purpose of the Study:
- To elucidate the mechanism behind impaired testicular steroidogenesis in Ddr2 mutant mice.
- To investigate the role of collagen type I (COL1) in the context of Ddr2 function and testicular steroidogenesis.
- To explore the correlation between Ddr2 expression and serum testosterone levels in human pathological testes.
Main Methods:
- Comparative analysis of Ddr2 and COL1 expression during postnatal development in wild-type and Ddr2slie/slie mice.
- Assessment of androgen deficiency and interstitial fibrosis in an experimental vasectomy model.
- In vitro functional assays using TM3 cells to evaluate testosterone production under varying Ddr2 and COL1 conditions.
- Correlation analysis of Ddr2 expression with serum testosterone levels in human pathological testes.
Main Results:
- Ddr2 expression increases with postnatal development, while COL1 expression decreases in adulthood in wild-type mice.
- In Ddr2slie/slie testes, COL1 is consistently detected, particularly in adulthood, contrasting with undetectable Ddr2.
- Ddr2slie/slie mice show earlier androgen deficiency and interstitial fibrosis post-vasectomy. In vitro, Ddr2 ablation decreases testosterone production with high COL1, while Ddr2 overexpression maintains it. Attenuated Ddr2 correlates with low serum T in humans.
Conclusions:
- Abnormal interstitial COL1 accumulation is implicated in the steroidogenic dysfunction observed in Ddr2slie/slie mutant testes.
- Ddr2 plays a crucial role in maintaining testicular steroidogenesis, particularly in the presence of COL1.
- Findings suggest a link between Ddr2, COL1, and human testicular dysfunction.
Related Concept Videos
01:05Type IV Collagen of Basal Lamina
A type IV collagen molecule has six alpha chains which can...
01:11Fibril-associated Collagen
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
01:22Connective Tissue Cell Types
Fat cells (adipocytes), smooth muscle cells (myoblasts), and bone cells (osteoblasts) are some connective tissue cell types. Some immune system cells...
01:26Extracellular Matrix
01:11Introduction to Connective Tissues
01:05Desmosomes