Increased Expression Of Dermatopontin And Its Implications For Testicular Dysfunction In Mice

Objective:Dermatopontin(DPT), a 22-kDa noncollagenous extracellular matrix protein that promotes cellular adhesion and extracellular matrix assembly. We previously showed that DPT is expressed in the Sertoli cells within the testis. An in vitro study showed that DPT is a novel regulator of the CdCl2-induced reduction in claudin-11 expression, which suggests that DPT maybe be related to testicular dysfunction. Therefore, the present study aimed to futher explore the implications of DPT expression for testicular function.Methods:1. The mice received busulfan administered via intraperitoneal injections to establish the testicular dysfunction models.2. The expression of DPT mRNA and protein in mice testes were detected using the Real-time PCR and Western blotting, respectively.3. To facilitate studies into the effects of endogenous DPT overexpression on testicular function, DPT overexpression transgenic mice models were established.4. Immunohistochemical detection was performed to examine the expression of DPT protein in testes of the DPT transgenic mice.5. HE staining was utilized to assess the changes of DPT transgenic mice testes.6. Western blotting was performed to measure the expression of Claudin-11 and ZO-1 in testes of DPT transgenic mice.Results:A positive correlation was found between degree of testicular damage and DPT expression level, which suggests that an increase in DPT expression may be a marker for testicular dysfunction. This result was corroborated by the finding that transgenic mice that have a Sertoli cell-specific overexpression of DPT exhibit damage to their testicular morphology. Moreover, DPT overexpression in the testis affected claudin-11 and zonula occludens-1 expression, which indicates that DPT may affect testicular function by affecting the integrity of the blood-testis barrier(BTB).Conclusions:The present study provided evidence to suggest that increased expression of dermatopontin was related to the testicular dysfunction. Increased expression of dermatopontin may induce the damage to the BTB, and then lead to the testicular dysfunction, which might be an indicator of mouse testicular dysfunction.