Imbalance of glucose homeostasis in the mother-placenta-fetus system in case of gestational diabetes mellitus (GDM) leads to pre- and postnatal abnormalities in offspring. Lack of universally recognized GDM-model complicates the search for pathogenetic means to prevent and correct abnormalities in offspring. A model using food load (high-calorie diet) in combination with low doses of diabetogen streptozotocin (HCD-STZ model) seems to be one of the closest in causes, mechanisms of development and clinical findings. Hence, the aim was to work out and assess the suitability of HCD-STZ model of GDM in order to register abnormalities in the offspring and determine the possibility of their pharmacological correction. Rats and its fetuses were the objects of the study. Modeling of GDM involved keeping rats on a high-calorie diet (NCD) for at least 10 weeks followed by a single injection of low-dose STZ on the first day of gestation. The hyperglycemia characteristic of GDM is recorded in less than 40 % of animals in HCD group combined with streptozotocin at a dose of 25 mg/kg. This fact does not allow a reliable assessment of abnormalities of antenatal and postnatal development of offspring. Thus, the model used is not promising for finding means of pharmacological correction of the effect of GDM on offspring.

Relevance. Gestational diabetes mellitus (GDM) is the most common complication of pregnancy. The lack of a biological model of GDM complicates the search for a suitable pharmacotherapy and presents the challenge of developing a valid model of this disease.Objective. The objective of this study was to develop a biological model of GDM accompanied by metabolic disorders in pregnant rats by using a high-calorie diet in combination with tyloxapol as diabetogenic factors.Materials and methods. GDM was modeled by keeping pregnant female Wistar rats on a high-calorie diet for at least 7 weeks in combination with intraperitoneal administration of tyloxapol at doses of 200 and 400 mg/kg on various days of pregnancy. In parallel we evaluated the dose dependence of the effects of tyloxapol by its single intraperitoneal administration to non-pregnant female Wistar rats at doses of 200, 300, 400 mg/kg.Results. The study showed that the optimal combination of a high-calorie diet with the administration of tyloxapol at a dose of 200 mg/kg is optimal for GDM induction. In this case, there is a marked violation of glucose tolerance, an increase in the levels of glucose, total cholesterol, triacylglycerides and low-density lipoproteins in the blood serum. A pronounced embryoletal effect was observed with tyloxapol at a dose of 400 mg/kg. The use of tyloxapol at a dosage of 300 mg/ kg did not lead to a change in the registered parameters.Conclusion. The proposed biomodel demonstrates the main pathognomonic symptoms of GDM and may be useful in studying the mechanisms of development and searching new treatments for this pathology.