Embryo

Effects of Progranulin on Blastocyst Hatching and Subsequent Adhesion and Outgrowth in the Mouse

Abstract
Using cDNA microarray methodology, we had previously shown that transcripts of progranulin gene (Grn, also known as acrogranin), a recently identified autocrine growth factor, were up-regulated in mouse blastocysts adhered to the filter membrane in an in vitro culture system. In this study, we investigated the expression and effects of progranulin on blastocyst hatching, adhesion and embryo outgrowth during the peri-implantation period in the mouse. During this time period, substantial amounts of Grn mRNA were present in both inner cell mass (ICM) and trophectoderm. Progranulin was exclusively localized to the surface of the trophectoderm at the stages of early and pre-/post-adhesion blastocysts as well as in both trophoblast cells and ICM of outgrowth embryos, which was secreted as a 88 kDa single form into the surrounding medium. NIH3T3 cells that had been transfected with a progranulin expression construct secreted the 88 kDa form of the protein, from which a 68 kDa form could be generated by deglycosylation. In vitro treatment of blastocysts with recombinant progranulin promoted blastocyst hatching, adhesion and outgrowth, whereas rabbit anti-mouse progranulin IgG reduced the incidence of blastocyst hatching, adhesion and outgrowth. Bromodeoxyuridine (BrdU) incorporation and immunodisection of ICM studies revealed that progranulin was effective on the trophectoderm, not ICM. These results indicate that progranulin is an important factor for the processes of blastocyst hatching, adhesion and outgrowth, and suggest that the effects of progranulin on blastocyst adhesion and outgrowth may have been triggered by the prior action of progranulin to induce hatching of the blastocysts.

Key words: Embryo • Cytokines • Early development • Growth factors • Implantation

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