Regeneration of muscle tissue of the external anal sphincter in experimental androgen deficiency

The aim of the study was to estimate the dynamics of reactive changes and regeneration processes of the muscle tissue of the external anal sphincter in rats under conditions of physiological norm and with androgenic insufficiency. Material and methods. The study was carried out on 40 mature laboratory male rats, which were divided into 3 groups: 1 – intact control group; 2 – control group, with damage to the external anal sphincter in animals with physiological testosterone levels and 3 – experimental, with simulated postnatal hypogonadism and damage to the sphincter. To assess reparative regeneration, material after damage was taken on days 3, 5, 7, 14, 21 and 30. Histological sections were stained with hematoxylin and eosin, as well as IHC-staining using monoclonal antibodies to the cell proliferation marker ki-67. Ultramicroscopic preparations were obtained according to standard preparation protocols. Digital data obtained during the morphological study were subjected to statistical processing. Results. Morphological changes that occur in muscle tissue against the background of androgen deficiency are more pronounced than with physiological testosterone levels. This manifests itself in more intense interstitial edema, prolongation of muscle fibers destruction and processes of post-traumatic inflammation. As a result, in the experimental group the formation of new muscle fibers slows down, and the wound space is filled with scar connective tissue, the volume of which is 10% greater than with physiological testosterone levels. Conclusion. Against the background of androgen deficiency, the mechanisms of reparative regeneration of the muscle tissue of the external anal sphincter are not violated, however, hypogonadism is a factor that enhances inflammatory processes and inhibits the process of muscle tissue recovery.  

1. Dedov II, Mel'nichenko GA, Rozhivanov RV, Kurbatov DG. The recommendations on diagnostics and treatment of male hypogonadism (deficit of testosterone). The project. Problems of Endocrinology. 2015 Nov 12;61(5):60–71. (In Russ.). doi: 10.14341/probl201561560-71

2. Demidova TY, Skuridina DV, Kasimova AM. Metabolic and cardiovascular features of the course of type 2 diabetes mellitus in men with hypogonadism. Медицинский совет. 2022 Jun 1;0(10):34–9 (In Russ.).

3. Lebedeva NB, Hoffman VV. Current understanding of the role of age-related hypogonadism in the development of cardiovascular diseases. Terapevtičeskij arhiv. 2021 Jan 10;93(1):79–83 (In Russ.). Doi: 10.26442/00403660.2021.01.200597

4. Rozhivanov RV. Syndrome of hypogonadism in males. Obesity and metabolism. 2014 Jun 15;11(2):30–4 (In Russ.). doi: 10.14341/OMET2014230-34

5. Suvorova GN. Zakonomernosti gistogeneza i regeneratsii pryamoi kishki i ee sfinkternogo apparata: avtoref. diss. dokt. biol. nauk. Saransk, 2001 (In Russ.).

6. Anawalt BD, Matsumoto AM. Aging and androgens: Physiology and clinical implications. Reviews in Endocrine and Metabolic Disorders. 2022 Dec;23(6):1123–37. doi: 10.1007/s11154-022-09765-2

7. Demling RH, Orgill DP. The anticatabolic and wound healing effects of the testosterone analog oxandrolone after severe burn injury. Journal of Critical Care. 2000 Mar;15(1):12–7. doi: 10.1053/jcrc.2000.0150012

8. Doulamis IP, Tzani A, Konstantopoulos P, Daskalopoulou A, Spinos T, Bletsa E, et al. Experimental hypogonadism: insulin resistance, biochemical changes and effect of testosterone substitution. Journal of Basic and Clinical Physiology and Pharmacology. 2019 May 1;30(3). doi: 10.1515/jbcpp-2018-0118

9. Rossetti ML, Steiner JL, Gordon BS. Androgen-mediated regulation of skeletal muscle protein balance. Molecular and Cellular Endocrinology. 2017 May;447:35–44. doi: 10.1016/j.mce.2017.02.031

10. Trinick TR, Feneley MR, Welford H, Carruthers M. International web survey shows high prevalence of symptomatic testosterone deficiency in men. The Aging Male. 2010 Sep 9;14(1):10–5. doi: 10.3109/13685538.2010.511325