Effects of the prenatal injection to laboratory mice of the synestrol subtoxic dose on ovaries of the offspring

Recent studies that analyze the cytotoxic and pro-carcinogenic effects of estrogens indicate an increased risk of ovarian cancer in those patients which are treatment and do not exclude the effect of excessive hormonal levels on the formation of morphological and functional changes in tissues and organs in future offspring. The aim of the study was to study the effects of the prenatal effects of subtoxic doses of synestrol on the general morphology, histometric and immunohistochemical parameters of the ovaries of the offspring of laboratory mice in the its postnatal reproductive period of ontogenesis. Pregnant female laboratory mice were divided into 3 groups. The control group of animals was once injected olive oil at a dose of 0,2 μg/kg intramuscularly. The first experimental group of animals was injected intramuscularly a single dose of synestrol at a dose of 25 μg/kg in the form of a 2% oil solution, the second experimental group was injected intramuscularly once a single subtoxic dose of synestrol of 40 μg/kg in the form of a 2% oil solution. All pregnant female mice were treatment drugs at the gestational stage of E11.5. A histological study of the preparations of the ovaries of the offspring of the first experimental group of mice showed a change in the ratio of the area of cortical substance relative to the area of the medullar substance with a decrease in the number of follicles at different stages of development compared with similar indicators of the offspring of the control group of animals. A single intramuscular injection of synestrol at a dose of 40 μg/kg in the offspring of the second experimental group led to an increase in the area of cortical and medullar substances of the ovaries, a decrease in the number of primordial, primary (unilaminar) follicles, in contrast to the ovaries of the control group. In histological sections of the ovaries of the second experimental group, hypertrophy and hyperplasia of granulosa cells, as well as teca interna follicles were observed. The appearance of atretic bodies, focal luteinization, indicating a real prenatal effect of the hormone on the postnatal structure of the organ, was noted in the cortical substance. A decrease in the activity of markers of cell proliferation, the transcription factor p53 of an anti-oncogene, indicated damage to ovarian functions at the level of their molecular genetic predictors. The results of the study generally showed that the effect of a subtoxic dose of synestrol at stage E11.5 of the prenatal period of development of the offspring of laboratory mice leads to persistent morphological changes in their ovaries in the postnatal reproductive period of ontogenesis.

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