Mouse Models of Gestational Diabetes Mellitus and Its Subtypes: Recent Insights and Pitfalls

Gestational diabetes mellitus (GDM) is currently the most common complication of pregnancy and is defined as a glucose intolerance disorder with recognition during pregnancy. GDM is considered a uniform group of patients in conventional guidelines. In recent years, evidence of the disease's heterogeneity has led to a growing understanding of the value of dividing patients into different subpopulations. Furthermore, in view of the increasing incidence of hyperglycemia outside pregnancy, it is likely that many cases diagnosed as GDM are in fact patients with undiagnosed pre-pregnancy impaired glucose tolerance (IGT). Experimental models contribute significantly to the understanding of the pathogenesis of GDM and numerous animal models have been described in the literature. The aim of this review is to provide an overview of the existing mouse models of GDM, in particular those that have been obtained by genetic manipulation. However, these commonly used models have certain limitations in the study of the pathogenesis of GDM and cannot fully describe the heterogeneous spectrum of this polygenic disease. The polygenic New Zealand obese (NZO) mouse is introduced as a recently emerged model of a subpopulation of GDM. Although this strain lacks conventional GDM, it exhibits prediabetes and an IGT both preconceptionally and during gestation. In addition, it should be emphasized that the choice of an appropriate control strain is of great importance in metabolic studies. The commonly used control strain C57BL/6N, which exhibits IGT during gestation, is discussed in this review as a potential model of GDM.