Degradation of estrogen receptor α in activated blastocysts is associated with implantation in the delayed implantation mouse model.
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 (ERα) 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 ERα in implantation-induced (activated) blastocysts; however, this ERα 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 ERα 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 ERα 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 ERα, occurs in activated blastocysts, while expression of other proteins, including Brca1, is maintained at the same stage.
Laboratory of Animal Breeding and Reproduction, Division of Animal Science, Faculty of Agriculture, Utsunomiya University, Utsunomiya, Tochigi 321-8505, Japan.
Kyosuke
K
Saito
Etsuko
E
Furukawa
Mitsuru
M
Kobayashi
Emiko
E
Fukui
Midori
M
Yoshizawa
Hiromichi
H
Matsumoto
D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism; D001755:Blastocyst / Q000187:drug effects / Q000378:metabolism*; D046149:Embryo Culture Techniques; D010065:Embryo Implantation, Delayed / Q000187:drug effects; D004624:Embryo Transfer; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D008813:Mice, Inbred ICR; D011247:Pregnancy; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology; D059748:Proteolysis; D015398:Signal Transduction; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D019313:BRCA1 Protein; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D061988:Proteasome Inhibitors; D025521:Tumor Suppressor Proteins; C491163:Bard1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
blastocyst; estrogen receptor α; implantation; pregnancy; proteolysis