The adiponectin receptor agonist, AdipoRon, promotes reproductive hormone secretion and gonadal development via the hypothalamic-pituitary-gonadal axis in chickens

Adiponectin is a key hormone secreted by fat tissues that has multiple biological functions, including regulating the energy balance and reproductive system by binding to its receptors AdipoR1 and AdipoR2. This study investigated the correlation between the levels of adiponectin and reproductive hormones in the hypothalamic-pituitary-ovarian (HPO) axis of laying hens at 4 different developmental stages (15, 20, 30, and 68 wk) and explored the effects of AdipoRon (an activator of adiponectin receptors) on the hypothalamic-pituitary-gonadal (HPG) axis and follicle and testicular Leydig cells in vitro and in vivo. The results demonstrated that the adiponectin level was significantly correlated with that of reproductive hormones in the HPO axis (e.g., GnRH, FSH, LH, and E2) in laying hens at 4 different ages. Moreover, AdipoRon could promote the expression of AdipoR1 and AdipoR2 and the secretion of reproductive hormones in the HPG axis, including GnRH, FSH, LH, P4, and T. AdipoRon could also upregulate the expression of genes related to follicular steroidogenesis (STAR, CYP19A1, CYP17A1, and CYP11A1), hepatic lipid synthesis (OVR, MTP), follicular lipid uptake (PPAR-g), and follicular angiogenesis (VEGFA1, VEGFA2, VEGFR1, ANGPT1, ANGPT2, TEK) in the oviposition period, and all of these findings were consistent with the results obtained from in vitro experiments after the transfection of small white follicles (SWFs) with AdipoRon. Furthermore, the results suggest that AdipoRon increases the diameter of testicular seminiferous tubules, the number of spermatogenic cells and sperm production in vivo and enhances the expression of AdipoR1, AdipoR2 and steroid hormones in vitro. Collectively, the findings suggest that AdipoRon could facilitate the expression and secretion of reproductive hormones in the HPG axis by activating its receptors and then improve the growth and development of follicles and testes in chickens.