Expression and function of interleukin-1β is required for hamster blastocyst hatching: Involvement of hatching-associated cathepsin proteases

Abstract

In mammals, the phenomenon of blastocyst hatching is an essential prerequisite for successful implantation. Blastocyst hatching is regulated by various molecules. Of them, cytokines, expressed by preimplantation embryos, are thought to be functionally important in blastocyst development and hatching, but their mechanistic roles are not clearly understood. Here, we examined the involvement of two cytokines, namely, interleukin-1β (IL-1β) and its natural antagonist, IL-1ra, in blastocyst hatching in the golden hamster. Blastocysts expressed both cytokines and their receptor, IL-1rt1. Supplementation of IL-1β to cultured eight-cell embryos improved blastocyst hatching (84.1% ± 4.2% vs. 66.6% ± 6.8%; treated vs. control). This improvement was diminished by IL-1ra treatment (23.6% ± 12.9% vs. 76.4% ± 12.9%; treated vs. control). Interestingly, IL-1β-treated embryos showed increased messenger RNA expression of zonalytic proteases, that is, cathepsin-L and -B by 1.9 ± 0.5- and 3.5 ± 0.1-folds, respectively. This was accompanied by their increased enzyme activities; cathepsin-L by 2.8 ± 0.7 fold and -B by 2.3 ± 0.7-fold. Strikingly, proteases and IL-1β were intensely colocalized to trophectodermal projections of hatching blastocysts. This is the first report to show the involvement of embryonic IL-1β in regulating hatching-associated proteases required for blastocyst hatching.

Keywords: hamster embryo; hatching failure; preimplantation development; proinflammatory cytokines; proteases.