Histone chaperone APLF level dictate implantation of mouse embryo

Abstract

Our recent findings demonstrated that histone chaperone and DNA repair factor Aprataxin PNK like factor (APLF) could regulate Epithelial to mesenchymal transition (EMT) during reprogramming of murine fibroblast and in breast cancer metastasis. So, we investigated the function of APLF in EMT associated with mouse development. Here we show that APLF is predominantly enhanced in trophectoderm and lineages derived from trophectoderm in pre and post-implantation embryos. Downregulation of APLF induced hatching of embryos in vitro with a significant increase in Cdh1 and Cdx2 expression. Aplf shRNA microinjected embryos failed to implant in vivo. Rescue experiments neutralized the knockdown effects of APLF both in vitro and in vivo. Reduced expression of Snai2, Tead4 and the gain in Cdh1 and sFlt1 level marked the differentiation of APLF-knocked down Trophoblast Stem Cells that might contribute towards the impaired implantation of embryos. Hence, our findings suggest a novel role of APLF during implantation and post-implantation development of mouse embryos. We anticipate that APLF might contribute to the establishment of maternal-fetal connection, as its fine balance is required to achieve implantation and thereby attain proper pregnancy.