Immunohistochemical study is one of the modern methods of disease diagnostics used in practical veterinary practice, as well as in scientific developments in differential diagnostics of animal diseases of tumour and non-tumour nature. Prenatal influence of estrogens results in reproductive system disorders in an adult organism which is accompanied by parallel growth of steroid dependent cancers of the offspring: testicles and ovaries. The aim of the study was to perform immunohistochemical analysis of Bcl-2 marker during prenatal exposure to different doses of the synthetic estrogen analogue Sinestrol in the testes of the offspring of white non-pedigreed laboratory mice. After fertilization, the pregnant females were divided into 3 groups, one intact and two experimental groups. The intact group was unaffected (n = 10). The first experimental group, C-25 (n = 13), was injected with the estrogen drug Sinestrol in the form of a 2 % oil solution at a dose of 25 g/kg. The second experimental group (n = 13) was given the estrogen preparation Sinestrol in the form of 2 % oil solution in a dose of 40 mkg/kg. When the offspring reached sexual maturity, they were removed from the experiment. Immunohistochemical analysis was carried out on sections from paraffin blocks of testes of progeny intended for standard morphological study, the marker of apoptosis inhibitor Bcl-2 was determined on indices of cellular elements of male glands of progeny: spermatogonia, spermatocytes, sperm-tides, spermatozoa and Leydig cells. Expression of Bcl-2 marker upon exposure to the synthetic drug Sinestrol at doses of 25 and 40 g/kg showed that the number of positively stained cells in spermatogonia increased by 8.6 and 9.4 % respectively compared to the intact group. When the intact group was compared with experimental groups C-25 and C-40, the expression of Bcl-2 marker in spermatocyte cells and spermatozoa showed no difference, a slight increase in positively stained cells in spermatids was observed. Bcl-2 marker expression rate in experimental groups C 25 and C-40 decreased in Leydig cells by 56.0 (P 0.05) and 60.0 % (P 0.05), respectively. Administration of the synthetic estrogen analogue Sinestrol during fetal gland initiation resulted in impaired morphology in the testes in adulthood. The expression index of Bcl-2 marker in experimental groups C-25 and C-40 decreased in Leydig cells, resulting in apoptotic cell death, which is responsible for production of male sex hormone testosterone. The results can be used to select optimal doses of the synthetic estrogen analogue Sinestrol in the prenatal period.
Relevance. Fulvestrant is used for the treatment of breast cancer in combination with other drugs. The aim of the study was to determine the effect of the prenatal action of fulvestrant on the ovaries of the offspring of laboratory mice. Materials and Methods. The experimental animals were divided into 4 groups: intact, control and 2 experimental, 5 animals in each group. Injections were administered to females after fertilization at the gestational stage E 11.5 once intramuscularly. In the control group (n=5), sterile castor oil was administered at a dose of 0.8 mcg/kg. In the first experimental group (n=5), an antiestrogen was introduced in the form of an oil solution of fulvestrant 0.08 ml 0.0005% at a dose of 20 mcg/kg. In the second group (n=5), an antiestrogen was introduced in the form of an oil solution of fulvestrant 0.4 ml 0.0005% at a dose of 100 mcg/kg. Results and Discussion . The study revealed that in the ovaries when the drug was administered at a dose of 20 mcg/kg (F-20), the number of primordial follicles was reduced. Accordingly, the number of follicles of subsequent generations decreased. With the introduction of the drug fulvestrant 100 mcg/kg (F-100) on the section of the ovary, sclerosis of the stromal component is observed, accompanied by a rearrangement of the vascular network with signs of atresia and cystic degeneration of the follicular epithelium in the secondary and tertiary follicles, formed cysts are observed in the ovarian parenchyma. Conclusion. The prenatal effect of the drug fulvestrant on the maternal body during pregnancy leads to persistent structural changes in the ovaries of the offspring, manifested in the late stages of ontogenesis, which, in turn, can lead to violations of reproductive function. The depth and scale of these changes are dose-dependent.
In the modern clinical practice there is an increase in the use of hormones, their analogues and substances with hormone-like action in medical practice for the regulation of the menstrual cycle, conception, prevention, maintenance and resolution of pregnancy. According to official reports, in recent years, the number of annual cycles of assisted reproductive technology with hormonal support has increased six times in the country. The purpose of the review is to summarize current data on the effects of experimental and clinical effects of various doses of estrogens and drugs with estrogenic effects during the period of prenatal development on the morphology of the reproductive organs of the offspring in postnatal ontogenesis. The materials for the meta-analysis of the data were the results of relevant studies of domestic and foreign authors and their own published data. The article summarizes current data demonstrating the effects of experimental effects of various doses of estrogen and drugs with an estrogenic effect during the period of prenatal development on the morphology of the reproductive organs of the offspring in postnatal ontogenesis. The data on therapeutic, subtoxic and toxic doses of the effects of estrogen preparations in various experimental models are summarized, causing latent and morphologically manifested changes in the reproductive organs of the offspring.
Background. The question of the effect of female sex hormones and their analogues on humans and experimental animals is of great interest in medicine. Aim. The aim of the work was to study the morphological features of the ovaries of the offspring of laboratory mice during the administration of estrogens to the maternal body. Materials and methods. Female laboratory mice after fertilization were divided into groups: two control and two experimental, which at the stage of development of gestation E11.5 underwent intramuscular, single administration of experimental doses of estrogens. The first experimental group was injected with the synthetic drug synestrol in the form of a 2% oil solution at a total dose of 50 mcg / kg (n = 5; S-50), the first control group was injected with olive oil at a dose of 0.2 m/kg (n = 5). The second experimental group was injected with a 0.4 ml 0.0005% fulvestrant oil solution at a dose of 100 mcg/kg (n = 5; F-100), the second control group (n = 5) received sterile castor oil at a dose of 0.8 m/kg. Results. Persistent morphological changes are observed in the ovaries of the offspring of the first experimental group S-50: an increase in the average area of the cortical substance, a decrease in the area of the medulla, an increase in the average number of yellow bodies, an increase in the average number of luteal cells in the yellow body, a decrease in the total number of follicles and atretic bodies, indicating a violation of the folliculogenesis process, an increase in the average diameter of blood vessels demonstrating increased blood circulation. With the introduction of the drug fulvestrant 100 mcg / kg in the second experimental group F-100, morphological changes in the form of an increase in the average area of the cortical substance, a decrease in the average area of the medulla, sclerosis of the stromal component, accompanied by a restructuring of the vascular network with signs of atresia and cystic degeneration of the follicular epithelium in secondary and tertiary follicles are considered on a slice of the ovaries of the offspring. Conclusions. The obtained results of the study confirm the urgency of the problem of implementing complex measures aimed at limiting the effects of estrogenetic drugs introduced into the maternal body during pregnancy, in order to prevent adverse effects on the development of the ovaries of offspring.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.