Reactive changes in testicular endocrinocytes after hypogonadism and its substitution therapy in experiment
https://doi.org/10.34680/2076-8052.2023.4(133).520-530
Abstract
This study is devoted to the morphofunctional substantiation of the model of male hypogonadism and the establishment of the effectiveness of its substitution therapy using morphological methods. There were 6 groups of adult male rats (4 individuals in each) studied. Four groups of rats were experimental. Under anesthesia, the left and right spermatic cords with the vascular bundle were tied with a temporary ligature, inducing hypogonadism. In the first two experimental groups of rats, the ligature was applied for 30 and 60 minutes (respectively). Animals of the other two experimental groups received substitution therapy by introducing kisspeptin K6. Animals of the third experimental group began to receive kisspeptin a few minutes after restoration of testicular blood flow (ex tempore), and the rats of the fourth group — after 3 days. The duration of substitution therapy was 7 days. In the right and left histological sections of the testis (n = 8), the number of viable and dying interstitial endocrine cells was counted (under the control of the ongoing immunohistochemical reaction with caspase 3), the percentage of these cell types from their total number was calculated, and the area of viable endocrinocytes was determined. The significance of differences in the median, upper and lower quartiles of the compared parameters was determined using the nonparametric Mann–Whitney test. It has been established that the modeling of male hypogonadism by applying a double-sided ligature to the vessels of the spermatic cord for 60 minutes and experiencing it by the animals for the next 10 days induces pronounced reactive changes and death of some interstitial cells, inhibition and cessation of spermatogenesis. Kisspeptin KS6, administered ex tempore and regularly after acute ischemia, has a protective effect on interstitial endocrinocytes, including anti-apoptotic, restoring spermatogenesis, probably through activation of the central links of the hypothalamic-pituitary-testicular axis.
About the Author
A. D. Lisovsky
Institute of Experimental Medicine
Russian Federation
Russian Federation
Saint Petersburg
References
1. Lotti F., Maggi M. Ultrasound of the male genital tract in relation to male reproductive health // Human Reproduction Update. 2015. 21(1). 56-83. DOI: 10.1093/humupd/dmu042
2. Lotti F., Maggi M. Ultrasound of the male genital tract in relation to male reproductive health // Human Reproduction Update. 2015. 21(1). 56-83. DOI: 10.1093/humupd/dmu042
3. Ohtaki T., Shintani Y., Honda S., Matsumoto H., Hori A., Kanehashi K., Terao Y., Kumano S., Takatsu Y., Masuda Y., Ishibashi Y., Watanabe T., Asada M., Yamada T., Suenaga M., Kitada C., Usuki S., Kurokawa T., Onda H., Nishimura O., Fujino M. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein- coupled receptor // Nature. 2001. 411. 613-617. DOI: 10.1038/35079135
4. De Roux N., Genin E., Carel J. C., Matsuda F., Chaussain J. L., Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54 // Proceedings of the National Academy os Sciences. 2003. 100(19). 10972-10976. DOI: 10.1073/pnas.1834399100
5. Seminara S. B., Messager S., Chatzidaki E. E., Thresher R. R., Acierno J. S., Shagoury J. K., Bo-Abbas Y., Kuohung W., Schwinof K. M., Hendrick A. G., Zahn D., Dixon J., Kaiser U. B., Slaugenhaupt S. A., Gusella J. F., O'Rahilly S., Carlton M. B., Crowley W. F., Aparicio S. A. J. R., Colledge W. H. The GPR54 gene as a regulator of puberty // The New England Journal of Medicine. 2003. 349(17). 1614-1627. DOI: 10.1056/NEJMoa035322
6. 1. Niktina I. L., Bayramov A. A., Khoduleva Yu. N., Shabanov P. D. Kisspeptiny v fiziologii i patologii polovogo razvitiya – novyye diagnosticheskiye i terapevticheskiye vozmozhnosti [Kisspeptins in physiology and pathology of sexual development – new diagnostic and therapeutic possibilities] // Reviews on Clinical Pharmacology and Drug Therapy. 2014. 12(4). 3-12. DOI: 10.17816/RCF1243-12
7. Magradze R. N., Lisovsky D. A., Lisovsky A. D., Popkovsky N. A., Bobkov P. S., Bayramov A. A., Droblenkov A. V. Reaktivnyye izmeneniya endokrinnykh kletok yaichnika pri eksperimental'nom ishemicheskom povrezhdenii [Reactive changes in the endocrine cells of the ovary in experimental ischemic injury] // Vestnik NovSU. 2022. 2(127). 38-42. DOI: 10.34680/2076-8052.2022.2(127).38-42
8. Guidelines for the experimental (preclinical) study of new pharmacological substances: a textbook for the system of postgraduate professional education of doctors. Federal Service for Supervision in the Field of Health and Social Development of the Federal State Institution Scientific Center for the Examination of Medical Products; under the general editorship of R. U. Khabriev. 2nd ed., reprint. and add. Moscow, Meditsina Publ.; Shiko Publ., 2005. 826 p.
9. Lebedev A. A., Blazhenko A. A., Golts V. A., Devyatshin A. S., Lebedev V. A., Kazakov S. V., Bayramov A. A., Khokhlov P. P., Bykov E. R., Shabanov P. D. Deystviye analogov kisspeptina na povedeniye Danio rerio [The effect of kisspeptin analogues on the behavior of Danio rerio] // Reviews on Clinical Pharmacology and Drug Therapy. 2022. 20(2). 201-210. DOI: 10.17816/RCF202201-210
10. Droblenkov A. V., Proshina L. G., Yukhlina Yu. N., Bayramov A. A., Shibaev P. D., Nikitina I. L. Testosteron-zavisimyye izmeneniya arkuatnogo yadra gipotalamusa i ikh obratimost' pri modelirovanii i muzhskogo gipogonadizma [Testosterone-dependent changes of the hypothalamic arquate nucleus and their reversibility in modeling and male hypogonadism] // Patologicheskaya fiziologiya i eksperimental'naya terapiya [Pathological physiology and experimental therapy]. 2017. 61(4). 21-30. DOI: 10.25557/IGPP.2017.4.8519
11. Magradze R. N., Lisovsky D. A., Lisovsky A. D., Popkovsky N. A., Bobkov P. S., Bayramov A. A., Droblenkov A. V. Modelirovaniye zhenskogo gipogonadizma putem ishemizatsii yaichnika i yeye morfofunktsional'noye obosnovaniye [Modeling of female hypogonadism by ovarian ischemia and its morphofunctional justification] // Reviews on Clinical Pharmacology and Drug Therapy. 2022. 20(3). 289-295. DOI: 10.17816/RCF203
12. Kauffman A. S., Gottsch M. L., Roa J., Byquist A. C., Crown A., Clifton D. K., Hoffman G. E., Steiner R. A., Tena-Sempere M. Sexual Differentiation of Kiss1 Gene Expression in the Brain of the Rat // Endocrinology. 2007. 148(4). 1774-1783. DOI: 10.1210/en.2006-1540
13. Kauffman A. S., Clifton D. K., Steiner R. A. Emerging ideas about kisspeptin– GPR54 signaling in the neuroendocrine regulation of reproduction // Trends in Neurosciences. 2007. 30(10). 504-511. DOI: 10.1016/j.tins.2007.08.001
14. Laws S. C., Beggs M. J., Webster J. C., Miller W. L. Inhibin increases and progesterone decreases receptor for gonadotropin-releasing hormone in ovine pituitary cultures // Endocrinology. 1990. 127(1). 373-380. DOI: 10.1210/endo-127-1-373
15. Quiñones-Jenab V., Jenab S., Ogawa S., Funabashi T., Weesner G. D., Pfaff D. W. Estrogen regulation of gonadotropin-releasing hormone receptor messenger RNA in female rat pituitary tissue // Molecular Brain Research. 1996. 38(2). 243-250. DOI: 10.1016/0169-328x(95)00322-j
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For citations:
Lisovsky A.D. Reactive changes in testicular endocrinocytes after hypogonadism and its substitution therapy in experiment. Title in english. 2023;(4(133)):520-530. (In Russ.) https://doi.org/10.34680/2076-8052.2023.4(133).520-530
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