Abstract
Premature ovarian insufficiency (POI) is condition of female hypogonadism. One of the reasons for the development of POI is anticancer chemotherapy. Currently, hormone replacement therapy is considered the most effective method of treatment POI, which, however, had a number of side effects, requires constant administration of pharmaceuticals, did not restore fertility and correct pathological changes in target organs. Therefore, the search for alternative methods of treatment based on the use of stem cells is promising. The aim of work was to compare the therapeutic effects of different methods of administration of mesenchymal stem cells isolated from adipose tissue (AT MSCs) in restoring sexual function, as well as the behavior of mice with chemotherapy-induced premature ovarian failure.
 Materials and methods. The investigation was carried out on BALB/c mice with a POI model induced by Cyclophosphamide and Busulfan. A histological examination of preparations of the ovaries and uterus was carried out. We studied the changes in the weight of mice, ovarian function, sexual activity, as well as the behavior of animals in anxiolytic and zoosocial tests after treatment with AT MSCs with intraperitoneal and intraovarian routes of administration.
 Results and discussion. It was shown that the effectiveness of the use of AT MSCs depends on the method of their administration at the treatment of POI induced by chemotherapy. More rapid and complete restoration of the morphological structure, sexual function, and behavioral responses were observed in mice with POI treated by intraovarial administration of AT MSCs.
Highlights
Most effective method of treatment of Premature ovarian insufficiency (POI) was hormone replacement therapy, which, had a number of side effects, was requires constant use of drugs, did not recover fertility and correction of pathological changes in target organs
POI was simulated by the method described by Xiao G.Y. et al [8], by administering Cyclo phosphamide in a dose of 200 mg/kg (Baxter Oncology, Germany) and Busulfan (Aspen Phar ma, Germany) in a dose of 20 mg/kg. 200 mg of Cyclophosphamide was dissolved in 20 ml of Phosphate-buffered saline (PBS), 20 mg of Busulfan was dissolved in 2 ml of Dimethyl sulfoxide (DMSO) was added, and 0,5 ml of each animal was injected intraperitoneally
The study of the dynamics of the body weight of mice showed that within 8 weeks the weight of animals in the control group was increased from 20,2 ± 1,1 to 22,5 ± 1,8 g (Fig. 2, a, group 1), in the POI model the weight of the animals was decreased up to 16,5 ± 1,2 g followed by slow recovery
Summary
Most effective method of treatment of POI was hormone replacement therapy, which, had a number of side effects, was requires constant use of drugs, did not recover fertility and correction of pathological changes in target organs. The study of the therapeutic effects of placental derivatives and intraperitoneal administration of AT MSCs in the recovery of sexual function in mice with a chemotherapy-induced POI model had been shown that complete recovery of sexual function did not occur [4]. The search for a more effective method for the treatment of POI using the intraovarial route of administration of AT MSCs was continued. The study of behavioral responses could provide indirect information about recovery of estrogen production in the body of POI mice after treatment with AT MSCs. The aim of work was to compare the the rapeutic effects of АT MSCs with intraperitoneal and intraovarial administration in recovery of sexual function and behavioral responses in mice with chemotherapy-induced POI
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