CHARACTERISTICS OF THE TRANSGENERATIONAL EFFECT OF THE TOXIC DOSE OF SYNESTROL ON THE MORPHOLOGY OF OVARIES IN THE EXPERIMENT

Abstract

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Background. The generality of the molecular genetic mechanisms of tissue development and the maintenance of the physiological balance of cell proliferation and apoptosis for embryonic histogenesis and carcinogenesis, as shown in numerous experimental studies and clinical observations, is the basis of the transgenerational prenatal programming effect of high concentrations of estrogens and their metabolites on the incidence of tumors in offspring. Aim. The aim of the study was to analyze the morphological and immunohistochemical changes in the ovaries under the influence of the experimental prenatal toxic level of steroid hormones during the critical period of their germinating and development. Material and Methods. The studies were carried out on pregnant mature males of laboratory mice, divided into control and experimental groups. To females mice of the experimental group were administered synestrol at a toxic dose of 50 μg per animal intramuscularly at stage E11.5. On the 90th day of postnatal life, ovaries were isolated and a some of general morpho-functional indices were assessed. In addition, the immunohistochemical activity of the reaction was evaluated for bcl2, PCNA and p53 receptors. Results and Discussion. As a result of the study, it was established that the histological pattern of the ovaries of the offspring of the experimental group, in contrast to the ovaries of the animals in the control group, is characterized by the presence of multiple foci of hemorrhage and the fullness of the vessels of the medulla layer of ovaries. The parenchyma of the ovarian cortex is represented by a large number of yellow bodies, the follicles with ovules are shifted to the periphery of the organ, the stroma of the cortex is significantly reduced and is represented by thin connective tissue interlayers between the follicles. In the organ was reduced the number of primary (unilateral) follicles, secondary (multilaminar) and tertiary follicles. In single cells of yellow bodies, a positive expression of the pro-oncogene marker p53 is observed. In the stroma of the organ, the high expression of this marker is up to 8%, in individual follicles the high expression of p53 is up to 15-20%, there is a proportional increase in the number of stained cell elements according to the stage of maturation of the follicles. Conclusions. The obtained data testify to the presence of a reliable positive transgenerational effect of injection a toxic dose of synestrol during the period of germinating and beginning of the morphogenesis of the ovaries of the offspring with the features of their structural and functional organization in late postnatal ontogenesis.