Leptin Promotes Primordial Follicle Activation by Regulating Ovarian Insulin-like Growth Factor System in Chicken

Leptin and insulin-like growth factor 1 (IGF-1) regulate follicle development and reproduction in vertebrates. This study investigated the role played by leptin and IGF-1 in primordial follicle activation in the ovary of 7-day-old chicks. Different doses of leptin were intraperitoneally administrated to female layer chicks, and further analyses were performed. While leptin administration did not affect hepatic leptin receptor (LEPR), growth hormone receptor (GHR), or IGF-1, the lower dose of leptin significantly increased the messenger RNA (mRNA) expression of IGF-1, IGF-1 receptor, and IGF-binding protein (IGFBP)-2 and attenuated anti-Müllerian hormone (AMH) gene expression in the ovary. Furthermore, the ovaries of the same age chicks were challenged with leptin and/or IGF-1 in vitro. Leptin at a lower dose increased the mRNA expression of IGF-1, LEPR, and leptin; 100 ng/mL leptin and 10 ng/mL IGF-1 alone or combined with leptin reduced IGFBP-2 mRNA expression. AMH gene expression was also reduced by all doses except 10 ng/mL leptin. Histological studies showed that a lower dose of leptin injection induced the primordial follicle growth in the ovary in vivo, and the number of primordial follicles was higher in all leptin treatments over control in vitro. Moreover, the luciferase assay revealed that leptin enhanced IGF-1 promoter activity in LEPR-expressing CHO-K1 cells. Collectively, these results indicate that leptin directly affects the IGF-1/IGFBP system and promotes primordial follicular growth in the ovary of early posthatch chicks. In addition, the follicular development by leptin-induced IGF-1 is, at least in part, caused by the suppression of AMH in the ovary.