Yaroshenko D. Development and functioning of testes in conditions of long-term action of bisphenol A in the experiment

The dissertation is devoted to establishing the features of pathological changes in spermatogenesis under conditions of prolonged toxic action of various doses of bisphenol A. The main attention of the work is aimed at revealing the features of changes in the histoarchitectonics of the testes, qualitative indicators of ejaculate and hormonal status, depending on the dose and duration of BPA exposure. Therefore, the aim of the work was to establish the features of structural and functional changes in the testes exposed to prolonged toxic effects of bisphenol A. The studies that were conducted as part of this experimental work met the requirements of the European Convention for the protection of vertebrates used for research and other scientific purposes (Strasbourg, March 18, 1986). All research procedures were carried out in accordance with international requirements and norms of humane treatment of animals. Directive No. 2010/63 / EC on the protection of animals used for scientific purposes (2010), law of Ukraine 3447-IU of 21.02.2006, and the conclusion of the commission on biomedical ethics of DSMU (Protocol No. 18 of 17.04.2024). The study used 120 male rats of The Wistar line aged 2-3 months, weighing 210-230 G. The selected rats were randomly divided into four groups: F0-1 – control group (n=30) – animals that were on a normal diet and additionally received corn oil – 2.5 mL/kg of body weight; F0-2 – intact group (comparison) (N=30) animals that were on a normal diet; F0-3 – experimental group (n=30) – experimental animals that were injected with bisphenol A for 120 days (Sigma-Aldrich, USA), dissolved in corn oil, dose – 50 mg/kg/day; F0-4 – experimental group (n=30) - animals that were administered bisphenol A dissolved in corn oil at a dose of 250 mg/kg/day for 120 days. BPA dissolved in corn oil was administered daily orally. Scientific novelty of the obtained results. For the first time, a complex of factors influencing the onset of pathological changes in spermatogenesis under conditions of prolonged toxic action of various doses of bisphenol A was determined on a representative experimental material. based on the obtained data, the understanding of the main characteristics of BPA-induced apoptosis of structural links of the seminiferous epithelium of rat testes is expanded. Data on the nature of the formation of a complex of disorders of spermatogenesis processes, which changed the hormonal status and reduced the level of fertility of animals, were clarified. For the first time, based on the integrated method of studying the histoarchitectonics of the testes, qualitative indicators of ejaculate and hormonal status, a model of the deployment of pathological changes in BPA-induced damage to the male reproductive system has been developed, which allows predicting the algorithm for the development of negative changes in spermatogenesis in the testes from the early stages of the deployment of pathological processes in the seminiferous epithelium to significant disorganization of spermatogenesis. When developing a model for the deployment of BPA-induced damage to the male reproductive system, based on correlation analysis of the experimental results obtained, revalent predictors of fertility were determined in rats treated with 250 mg/kg/day. Five independent factors were identified that had a strong correlation with the indicator of the level of fertilization capacity of sperm, in particular: the number of the fraction of abnormal forms (rs=-0.853; p<0.001), the fraction of progressive motile spermatozoa (respectively rs=0.782; p<0.001), non-progressive motile spermatozoa (respectively rs=-0.780; p<0.001), fixed sperm fraction (rs=-0.791; p<0.001), and height of seminiferous epithelium (rs=-0.782; p<0.001). Theoretical and practical value of the work. The results of the study of pathological changes in spermatogenesis allowed us to form the main characteristics of BPA-induced apoptosis of structural links of the seminiferous epithelium of rat testes, on the basis of which a model for the deployment of BPA-induced damage to the male reproductive system was developed. Visualization of the development of symptoms of pathological processes of spermatogenesis, as a result of testicular intoxication, makes it possible to increase the effectiveness of diagnostic guidelines of clinical practice for determining the level of fertility. The revealed possibilities of fertilizing the sperm capacity of rats exposed to various BPA-induced testicular damage provide additional tools for in-depth study of the male reproductive system in specialized research laboratories