The Goto-Kakizaki rat is a spontaneous prototypical rodent model of polycystic ovary syndrome
Camille Bourgneuf, Danielle Bailbé, Antonin Lamazière, Charlotte Dupont, Marthe Moldes, Dominique Farabos, Natacha Roblot, Camille Gauthier, Emmanuelle Mathieu d’Argent, Joëlle Cohen-Tannoudji, Danielle Monniaux, Bruno Fève, Jamileh Movassat, Nathalie di Clemente, Chrystèle Racine
Abstract
Polycystic ovary syndrome (PCOS) is characterized by an oligo-anovulation, hyperandrogenism and polycystic ovarian morphology combined with major metabolic disturbances. However, despite the high prevalence and the human and economic consequences of this syndrome, its etiology remains unknown. In this study, we show that female Goto-Kakizaki (GK) rats, a type 2 diabetes mellitus model, encapsulate naturally all the reproductive and metabolic hallmarks of lean women with PCOS at puberty and in adulthood. The analysis of their gestation and of their fetuses demonstrates that this PCOS-like phenotype is developmentally programmed. GK rats also develop features of ovarian hyperstimulation syndrome. Lastly, a comparison between GK rats and a cohort of women with PCOS reveals a similar reproductive signature. Thus, this spontaneous rodent model of PCOS represents an original tool for the identification of the mechanisms involved in its pathogenesis and for the development of novel strategies for its treatment.