Evaluation of the pharmacological activity of a somatostatin-containing protein-based preparation in a model of cyclophosphamide-induced ovarian failure in female mice

According to statistical studies, the number of infertile couples in the world is constantly growing and accounts for approximately 15%. Female infertility makes up 20–35%. The new drug being developed on the basis of somatostatin-containing protein is supposed to be used in female and male infertility, to increase the reproductive capacity of the body, to enhance the ovarian reserve and their entry into the growth phase, to accelerate the beginning of growth of resting follicles, to expand the volume of ejaculate and improve the quality characteristics of sperm.

Objective: Evaluation of the pharmacological activity of a somatostatin-containing protein-based preparation in a model of cyclophosphamide-induced ovarian failure in female mice.

Materials and methods: The drug "Endoxan" was used as an inducer of pathology once intraperitoneally at a dose of 70 mg/kg. Six groups were formed for the study: 1st – intact (n=15); 2nd – negative control (pathology+sodium chloride solution 0.9%, n=10); 3rd – positive control (pathology+recombinant murine somatotropic hormone at a dose of 800 µg/kg, n=10); 4th – pathology+test subject at a dose of 10 µg/kg (n=15); 5th – pathology+test subject at a dose of 50 µg/kg (n=15), 6th – pathology+test subject at a dose of 250 µg/kg (n=15).

The study included evaluation of microscopic changes in ovarian tissue, ovarian mass ratios, morphometric analysis of follicles, and plasma PGE₂ and somatotropin levels.

Results: It was found that against the background of induced pathology the tested drug in the dose range of 10–250 µg/kg leads to a dose-dependent increase in the level of somatotropin and PGE₂ and normalisation of folliculogenesis. It was revealed that a significant increase in the proportion of primordial and tertiary follicles and a decrease in the proportion of atretic follicles occurred under the effect of the tested preparation. This suggests a possible mechanism of action of the tested object, namely the synthesis of specific autoantibodies to somatostatin and a decrease in its concentration. This in turn leads to an increase in the content of endogenous somatotropic and sex hormones in the body.

Conclusion: The results obtained are consistent with the data of earlier studies on the increase in the size and number of follicles upon administration of exogenous somatotropic hormone to animals. We believe that clinical studies of the possibility of using a preparation based on somatostatin-containing protein for the treatment of female infertility associated with disorders of folliculogenesis are necessary.