Embryo-Dependent Induction of Uterine Receptivity Assessed by an in Vitro Model of Implantation in Mice1

To investigate the molecular basis of initial interactions between the trophoblast and the uterine epithelium at implantation, we developed an in vitro model for implantation in mice using primary uterine organ cultures as the substrate. In this model, embryos attached to the endometrial explants within 60 min. We were able to observe the attachment between embryos and endometrial explants in real time. Using this model, we investigated the attachment of embryos to uterine strips cultured from pregnant mice, pseudopregnant mice, pseudopregnant mice that had received hCG injections, and pregnant mice whose utero-tubal junctions had been ligated on Day 2 of pregnancy. The serum levels of progesterone in pregnant and pseudopregnant mice were also compared. The percentages of embryos that attached to uterine strips cultured from pregnant mice on Days 1–4 were low (0.0–15.0%). However, by Days 5–7, percentages of attachment increased markedly (66.8–74.8%). These levels were significantly higher than those observed for pseudopregnant mice (0.0–18.0%) and pseudopregnant mice that had received hCG injections (0.0–15.0%). The percentages of attachment to the ligated horns of pregnant Day 5 uteri (58.3–61.5%) were significantly higher than that of pseudopregnant mice (10.0%). The percentages of attachment to the ligated horns of pregnant Day 6 and 7 uteri decreased significantly (3.2%–19.4%). On the other hand, the percentages of attachment to the unligated horns of pregnant Day 6 and 7 mouse uteri did not decrease significantly (61.1–70.0%). The serum progesterone levels of pseudopregnant mice were not significantly lower than those of pregnant mice on Days 1–5. These results suggest that endometrial receptivity appears on Day 5 of pregnancy and an embryonic factor(s) is involved in the acquisition of receptivity by surface epithelium, but direct contact between the embryo and the endometrium is not essential. These results also suggest that the appearance of endometrial receptivity is transient, and when embryo-endometrial interactions have not taken place, endometrial receptivity will be lost on Day 6 of pregnancy. On the other hand, when embryo-endometrial interactions do take place, endometrial receptivity will continue through Days 6 and 7 of pregnancy.