Progesterone supplementation extends uterine receptivity for blastocyst implantation in mice

We previously showed that blastocyst can initiate implantation beyond the normal 'window' of uterine receptivity on day 5 of pregnancy and pseudopregnancy (PSP) in mice. In this study, we investigated whether uterine receptivity for blastocyst implantation can be further extended on day 6 of PSP and the role of progesterone (P(4)) on this event. Embryo transfers, experimentally induced decidualization, in situ hybridization and [(3)H]thymidine incorporation were performed. Blastocysts initiate attachment reaction within 48 h when transferred on day 5, but not on day 6 of PSP. Likewise, decidualization reaction occurred on days 4 and 5 of PSP, but completely failed on day 6. However, P(4) supplementation partially retains uterine receptivity for blastocyst implantation and decidualization on day 6 of PSP. In addition, certain indicators of uterine receptivity, such as cell proliferation profile and expression patterns of implantation-related genes were similarly observed on days 4 and 5 of PSP, but not on day 6. Consistent with embryo transfer and decidualization, exogenous administration of P(4) partially restores these indicators on day 6 of PSP. We concluded that critical physiological changes occur between days 4 and 5 of PSP, leading to uterine non-receptivity on day 6, but P(4) is able to extend the uterine receptivity through day 6.