Nociceptin Induces Rec8 Phosphorylation and Meiosis in Postnatal Murine Testes

Abstract

Phosphorylated Rec8, a key component of cohesin, mediates the association and disassociation, "dynamics," of chromosomes occurring in synaptonemal complex formation, crossover recombination, and sister chromatid cohesion during meiosis. Yet, the extrinsic factors triggering meiotic chromosome dynamics remain elusive. We have recently found that nociceptin, known as a neuropeptide, is up-regulated by follicle-stimulating hormone in Sertoli cells in postnatal murine testes; however, very little is known about the functional role of nociceptin in spermatogenesis. Here, we show that nociceptin induces Rec8 phosphorylation, triggering chromosome dynamics, in spermatocytes during meiosis in postnatal murine testes. The nociceptin receptor Oprl-1 is exclusively expressed in the plasma membrane of testicular germ cells, mostly spermatocytes. Treatment of testes with nociceptin resulted in a rapid phosphorylation of Rec8. Injection of nociceptin into mice stimulated Rec8 phosphorylation and meiotic chromosome dynamics in testes, whereas injection of nocistatin, a specific inhibitor of nociceptin, abolished them. These findings suggest that nociceptin is a novel extrinsic factor that plays a crucial role in the progress of meiosis.