Enhancing the developmental competence of the early embryo using secretory leukocyte peptidase inhibitor

Abstract

Secretory leukocyte peptidase inhibitor (SLPI) plays a role in proliferation and differentiation via the autocrine and paracrine systems. SLPI's expression is well-documented in the reproductive tract, but it remains unclear whether it is active during early embryonic development. In this study, the expression and role of Slpi in the early embryo were evaluated. In vitro embryo cultures in chemically defined simple medium resulted in a reduction in developmental speed from the 8-cell stage, as well as implantation rate compared with in vivo embryos. SLPI protein was localized to the membrane or submembrane cytoplasm in an embryonic stage-dependent manner. In vitro cultured embryos exhibited lower levels of Slpi mRNA expression than in vivo embryos. Slpi knockdown by antisense oligonucleotides attenuated the developmental speed and implantation rate compared with Slpi sense oligonucleotide-transfected embryos and in vitro controls. The critical period for the attenuation of developmental speed occurred after the 8-cell stage. SLPI treatment accelerated development, increased implantation rate, and ameliorated the suppressive effects of Slpi knockdown. Slpi knockdown did not induce changes in the total cell number or inner cell number in blastocysts. Meanwhile, SLPI upregulated the expression of the developmental factors matrix metalloproteinase-14, neutrophil elastase, and tissue inhibitor of metalloproteinase-1. Together, these results suggest that SLPI is an effective regulator of developmental speed and implantation competence in an autocrine and paracrine manner, respectively, and plays a role in controlling the expression of embryonic development factors, such as MMP family members.