Gonadotropin inhibitory hormone (GnIH) induces glucose metabolism disorders and ovarian dysfunction in ovarian white follicles of hens

Energy metabolism is crucial for reproduction, and disturbances in glucose metabolism are closely associated with reproductive disorders. The gonadotropin inhibitory hormone (GnIH) plays a crucial role in reproduction and glucose homeostasis in both birds and mammals. However, its specific effects on glucose metabolism-associated ovarian dysfunction in hens remain uncharacterized. In this study, we investigated the effects of GnIH on ovarian function and glucose homeostasis in hens using combined in vivo and in vitro approaches. Our results showed that GnIH and its receptor, GPR147, are predominantly expressed in white follicles. Continuous GnIH injection significantly reduced the ovarian index and the number of prehierarchical follicles, concurrently suppressing Fshr and LHr expression in white follicles. Additionally, metabolomic analyses indicate changes in key glucose metabolism pathways, indicating a regulatory role of GnIH in glucose metabolism. To validate our metabolomics findings, the effects of GnIH on glucose homeostasis in ovarian white follicles and granulosa cells (GCs) were further investigated through in vivo and in vitro studies. The results demonstrated that GnIH enhanced glucose transport, glycolysis and glycogen synthesis, but concurrently induced insulin resistance, oxidative stress, and mitochondrial dysfunction, ultimately leading to reduced energy levels and apoptosis in ovarian tissues. In summary, our study reveals that GnIH contributes to ovarian dysfunction via glucose metabolism dysregulation in hens, suggesting its potential as a therapeutic target for metabolic disorder-associated ovarian impairment in chickens.