CREATION OF THE PREGNANCY MICE MODEL TO STUDY THE EFFECT OF GLP-1/GIP AGONISTS

Abstract

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists represent a novel class of antidiabetic and anti-obesity agents. Despite their growing clinical relevance, little is known about their safety and potential effects during pregnancy. Here we describe the development of a pregnancy mouse model to study the impact of GLP-1/GIP dual agonists, with a focus on maternal metabolic changes, embryonic development, and organ-specific outcomes. Introduction. The use of GLP-1 and GIP receptor agonists has expanded significantly due to their efficacy in improving glycemic control and reducing body weight. Tirzepatide, a dual GLP-1/GIP agonist, has shown remarkable clinical outcomes in type 2 diabetes and obesity. However, its safety profile during pregnancy remains poorly understood. Pregnancy is a unique physiological state characterized by altered glucose homeostasis, increased insulin resistance, and complex hormonal regulation. Drug exposure during this period can impact both maternal health and fetal development. Current clinical guidelines recommend discontinuing GLP-1 receptor agonists during pregnancy, but preclinical data are limited. Aim. This work aims to establish a reproducible mouse pregnancy model to evaluate the effects of GLP-1/GIP agonists, such as Tirzepatide, on maternal physiology and embryonic outcomes. Materials and Methods. Animals: C57BL/6 female mice, aged 8–10 weeks, were used. Females were mated overnight, and pregnancy was confirmed by vaginal plug observation (defined as embryonic day 0.5, E0.5). Experimental Groups: Control group – intraperitoneal injections of PBS, GLP-1/GIP agonist group – intraperitoneal injections of Tirzepatide. Treatment Protocol: Injections were administered daily starting from E13.5 until E17.5. On embryonic day 17.5, pregnant mice were sacrificed, and maternal organs, placenta, and embryos were collected for further analysis. Endpoints: Maternal body weight and food intake; Fetal number, size, and weight; Placental weight and morphology; Maternal organ collection for histological and molecular studies. Results. A reproducible mouse pregnancy model to evaluate the effects of GLP-1/GIP agonists (Tirzepatide) on maternal physiology and embryonic outcomes was created. Pregnant mice were successfully treated with PBS, Tirzepatide according to the protocol. On E17.5, animals were sacrificed, and maternal/fetal samples were collected. Data analysis, including weight measurement, morphological assessment, and molecular profiling, is ongoing. Conclusion. We established a pregnancy mouse model suitable for studying the impact of GLP-1/GIP dual agonists. This approach will generate critical preclinical data to evaluate maternal-fetal safety and mechanistic insights.