Role of cathepsins in ovarian follicle growth and maturation

Several complex processes are involved in the production of viable eggs. The aim of this review is to provide an overview on the role played by lysosomal enzymes, especially cathepsins B, D, and L, during ovarian follicle growth and maturation. Specific attention is focused on the relationship between the second proteolytic cleavage of yolk proteins (YP) and the resumption of the meiosis during germinal vesicle break down (GVBD). Maturation represents the final stage of oocytes development prior to ovulation. Oocytes in this phase appear translucent. In many teleosts GVBD is accompanied by water uptake and among marine teleosts with pelagic eggs, most of the final volume is reached by this process. The last phase of maturation in benthonic eggs also occurs concomitant to a second proteolytic cleavage and is related with a slight hydration process. In vitro maturation by 17α,20β-dihydroxy-4-pregnen-3one in class III Danio rerio oocytes, induced 80% of GVBD. The maturation of these oocytes is known to be associated with proteolysis of their major yolk components. In the present study, we show that inhibition of specific enzymes (cathepsins) involved in the second YP processing, did not affect the occurrence of GVBD as the oocytes become translucent and display a slight increase in size. More specifically, in vitro incubation of the maturing oocytes with a cathepsin B inhibitor suppressed both cathepsin B and L activities and the proteolysis of YP. On the contrary, the addition of cathepsin L inhibitor, only affected cathepsin L activity, indicating that cathepsin B is probably involved in Cathepsin L activation, and this enzyme is probably responsible for the second YP processing. These results, together with previous studies, indicate that the GVBD process is independent of the occurrence of the second proteolytic process. It supports the hypothesis that the maturation process is under K+ ion flux control, while yolk proteolysis is related to the temporal and specific activation of cathepsins by acidification of yolk spheres.