Leptin enhances oocyte nuclear and cytoplasmic maturation via the mitogen-activated protein kinase pathway

Recent studies have suggested that leptin has a central role in female reproduction, including ovarian function. The leptin receptor (Ob-R) has six isoforms and can signal through either the MAPK or the Janus-activated kinase/signal transducer and activator of transcription signal-transduction pathway, depending on the isoform. Expression of Ob-R has been reported in human and mouse oocytes; however, the physiological role of leptin during follicular development and oocyte maturation is largely unknown. In the current study, expression of Ob-R during oocyte growth and maturation was investigated in porcine oocytes from small, medium, and large follicles and in oocytes in the germinal vesicle (GV), GV-breakdown, and metaphase II (MII) stages at both the mRNA and protein levels. The proportion of oocytes expressing Ob-R was maximal in oocytes from medium follicles and at the GV breakdown stage (P < 0.05), whereas the proportion of oocytes expressing the long isoform, Ob-Rb, was found to be consistently low throughout growth and maturation. When included in oocyte maturation medium, leptin significantly increased the proportion of oocytes reaching MII (P < 0.01), elevated cyclin B1 protein content in MII-stage oocytes (P < 0.05), and enhanced embryo developmental potential (P < 0.05), suggesting that leptin plays a role in both nuclear and cytoplasmic maturation. During oocyte maturation, leptin increased phosphorylated MAPK content by 2.8-fold (P < 0.05), and leptin-stimulated oocyte maturation was blocked when leptin-induced MAPK phosphorylation was suppressed by a specific MAPK activation inhibitor, U0126 (P < 0.01), demonstrating that leptin enhances nuclear maturation via activation of the MAPK pathway.