Andrology. 2022 Jan 22. doi: 10.1111/andr.13157. Online ahead of print.
ABSTRACT
BACKGROUND: There is limited data regarding the effects of systemic androgens on late-stage urethral wound healing.
OBJECTIVE: To evaluate the effects of systemic androgens on fibrosis, and scar formation in late-stage urethral wound healing.
MATERIALS AND METHODS: Forty-five male Sprague-Dawley rats were divided into 3 groups. First group consisted of 15 rats that were castrated on the 23 days of age and were given 5 mg/kg testosterone undecanoate with 1/25 ml cottonseed oil intraperitoneally at weekly intervals for 3 weeks. (CAS+T group). The CAS group included 15 castrated rats. The remaining 15 rats underwent sham surgery. CAS and Sham groups also received 1/25 ml cottonseed oil intraperitoneally at weekly intervals for 3 weeks. Furthermore, all groups were divided into 3 subgroups after testosterone/placebo administration (Urethroplasty performed after 1st , 2nd and 3rd weeks) in accordance with the urethroplasty timing. All animals were sacrificed 6 weeks after urethroplasty. Serum testosterone level was measured, tissue samples were investigated using H&E and Masson’s trichrome. Alpha-SMA, Coll 1 and Coll 3 primary antibodies were applied for immunohistochemical examination. Expression of cytokines and growth factors such as Bax, Bcl2, IL-10, IP-10, TNF-alpha, TGFb1, MMP9, Col-I, Col-III, TIMP-1, Fibronectin, FGF-10, PDGF, alpha-SMA were also evaluated in the tissues.
RESULTS: The blood testosterone levels were significantly higher in CAS+T group at the time of urethroplasty compared with the levels in CAS group however, this difference was not observed at the time of sacrification (p<0.001 and p:0.97, respectively). Histological analysis with Hematoxylin and eosin, Masson’s trichrome staining revealed a significantly higher fibrosis in the sham group compared to the others. Significantly lower fibrosis was detected in the CAS group in the pairwise comparison of the pathological fibrosis area between the CAS, and CAS+T groups (p<0.001). Furthermore, tissue collagen-1, collagen-3 and alpha-SMA expression levels were statistically different between CAS and CAS+T groups (p<0.001, p<0.05 and p<0.001, respectively). The tissue levels of BAX, TIM-1, MMP-9, Coll-I, Coll-III, TGF-beta, TNF-alpha and IL-10 mRNA expressions in the CAS+T group were different than the levels in CAS group (as <0.5-fold and >1.5-fold changes, respectively). The expression of all these markers were significantly higher in the sham group. The sub-group analysis of CAS+T group (Urethroplasty performed after 1st , 2nd and 3rd weeks) revealed similar histopathological wound healing findings.
DISCUSSION: Debate continues on the effects and benefits of androgen use regarding urethral healing. There are two main routes for administration as systemic or local. This study focuses on the late-stage histologic and biochemical effects of systemic androgens.
CONCLUSION: Systemic androgens adversely affect wound healing, and cause abnormal ECM as well as scar formation. This article is protected by copyright. All rights reserved.
PMID:35064654 | DOI:10.1111/andr.13157
