New insights into the roles of CUL1 in mouse placenta development.

CULLIN1 (CUL1) protein, as a scaffold protein in Skp1-CUL1-F box (SCF) E3 ligases complex, was reported involved in different cellular functions to regulate the early embryonic development. In our previous study, we have demonstrated that CUL1 promote trophoblast cell invasion at the maternal-fetal interface in human and the CUL1 protein significantly decreased in preeclampsia (PE) placenta, but how CUL1 involved in placentation is still obscure. Due to the embryo lethal in CUL1 knockout mice, the lentivirus mediated placenta-specific CUL1 knockdown mice model was constructed to uncover the potential role of CUL1 in placentation. In this study, CUL1 was first detected in mouse placenta. CUL1 mainly expressed in trophoblast giant cell at E9.5, and spongiotrophoblast at E11.5 and E13.5 by using immunohistochemistry and int situ hybridization. In lentivirus mediated placenta specific mouse model, the number of implanted embryos was reduced in CUL1 shRNA group at E13.5 and E18.5 compared to control group. Based on the morphological analysis of histologic staining, we observed that spongiotrophoblast layer is expanded, fetal angiogenesis in labyrinth was obstructed and fetus blood cells were accumulated in vessels. These results indicated that decreased expression of CUL1 affect placentation of mice, which give new insights into the cause of gestational diseases, but the exactly mechanism still needs further study.