Inhibition of ghrelin signaling improves the reproductive phenotype of male ob/ob mouse

ObjectiveTo investigate whether ghrelin signaling is involved in the pathogenesis of male factor infertility induced by leptin deficiency.DesignExperimental study.SettingUniversity academic medical center.Animal(s)Ten-week-old C57BL/6J mice and ob/ob mice.Intervention(s)Western blotting, (quantitative) reverse transcription–polymerase chain reaction (qRT-PCR), immunohistochemistry, and in situ end labeling of fragmented DNA.Main Outcome Measure(s)Expression levels of ghrelin and its functional receptor growth hormone (GH) secretagogue receptor 1a (GHS-R1α) were examined by Western blotting and immunohistochemistry. Ob/ob mice were injected IP with specific GHS-R1α antagonist, and thereafter germ cell apoptosis and steroidogenic capability were assessed by TUNEL assay, (q) RT-PCR, and radioimmunoassay.Result(s)Expression of GHS-R1α and its endogenous ligand ghrelin was both up-regulated in ob/ob testis. Inhibition of the ghrelin pathway restored androgen synthesis, reduced germ cell apoptosis, and thereby resulted in improved sperm production in ob/ob mice.Conclusion(s)Ghrelin, as an antagonistic partner of leptin in the endocrinic/paracrine circuit, may be involved in the pathogenesis of male factor infertility induced by leptin deficiency.