The developmental expression of the CDK inhibitor p57kip2 (Cdkn1c) in the early mouse placenta

SUMMARY p57 kip2 (encoded by the Cdkn1c gene) is a member of the cip/kip family of cyclin‐dependent kinase inhibitors that mediates cell cycle arrest in G1, allowing cells to differentiate. In the placenta, p57 kip2 is involved in endoreduplication, formation of trophoblast giant cells, trophoblast invasion, and expansion of placental cell layers. Here, we quantitatively and qualitatively define the cell‐ and region‐specific expression of mouse placental p57 kip2 using laser‐capture microdissection, in situ hybridization, and immunohistochemistry. Cdkn1c RNA was quantified by real‐time quantitative PCR. Co‐expression of Pl1 was used to identify trophoblast giant cells while Tbpba was used to identify spongiotrophoblast cells. Timed sacrifices were also carried out at embryonic days E7.5, E8.5, E9.5, and E12.5 to profile the expression in embryos and their placentas. At E8.5, intense expression of Cdkn1c was seen in invasive TGCs and the ectoplacental cone. Cdkn1c expression was more diffuse and more abundant in the labyrinth that in the junctional zone at both E9.5 and E12.5. Immunohistochemistry revealed robust p57 kip2 staining in trophoblast giant cells and in the ectoplacental cone at E8.5. p57 kip2 protein was seen in giant cells and throughout the labyrinth, although its abundance was reduced in the junctional zone at E9.5, and became more diffuse by E12.5. The early and intense expression in trophoblast giant cells is consistent with a role for p57 kip2 in the invasive phenotype of these cells. Mol. Reprod. Dev. 83: 405–412, 2016. © 2016 Wiley Periodicals, Inc .