Degradation of estrogen receptor α in activated blastocysts is associated with implantation in the delayed implantation mouse model

Abstract

Implantation of a blastocyst into a receptive uterus involves a series of highly coordinated cellular and molecular events directed by ovarian estrogen and progesterone. In particular, estrogen is essential for on-time uterine receptivity and blastocyst activation in mice. Although estrogen receptor α (ER α) is expressed in blastocysts, its targeted disruption leaves embryonic development and implantation unaffected. Therefore, the role of ERα in implanting blastocysts remains unclear. Using a delayed implantation model in mice, we showed increased expression of ER? in implantation-induced (activated) blastocysts; however, this ER α expression in activated blastocysts decreased within 6-h culture. In contrast, breast cancer 1 (Brca1) was maintained in the blastocysts during the culture. The treatment of activated blastocysts with the proteasome inhibitor MG132 demonstrated that proteolysis is associated with down-regulation of ER α expression in activated blastocysts. Embryo transfer of MG132-treated activated blastocysts into recipient mice on the morning of Day 4 of pseudopregnancy (Day 1 = vaginal plug) showed a decreased implantation rate, whereas combined treatment with MG132 and the ER antagonist, ICI 182,780, resulted in recovery of the rate of implantation. This study has revealed that down-regulation of ER? in activated blastocyst is associated with completion of blastocyst implantation after embryo transfer on the morning of Day 4 of pseudopregnancy. Our results also suggest that selective protein turnover, such as that of ER α, occurs in activated blastocysts, while expression of other proteins, including Brca1, is maintained at the same stage. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.