BLASTOCYSTS STATE OF ACTIVITY DETERMINES THE WINDOW OF IMPLANTATION IN THE RECEPTIVE MOUSE UTERUS

The present investigation studied the influence of the blastocyst's st ate of activity on the ''window'' of implantation in the receptive ute rus in the mouse. The receptive state of the uterus is defined as the limited time when the uterine milieu is favorable to blastocyst accept ance and implantation. In the mouse, implantation occurs on day 4 (day 1 = vaginal plug). Ovariectomy in the morning of day 4 prior to preim plantation estrogen secretion results in blastocyst dormancy and delay ed implantation. These conditions are maintained by continued progeste rone (P4) treatment but can be terminated with an injection of estroge n leading to blastocyst activation and subsequent implantation. Blasto cyst transfers into intact pseudopregnant mice demonstrated that the w indow of implantation on day 4 remains open at least through 1800 h fo r normal day 4 blastocysts but only up to 1400 h for dormant blastocys ts. These results suggested that the blastocyst's state of activity in fluenced the normally operative window of implantation in the receptiv e uterus. This finding was further confirmed by inducing conditions of delayed implantation in pregnant donors and pseudopregnant recipients . They were ovariectomized on the morning of day 4 and maintained with daily injections of P4 from days 5 to 7. On day 7, dormant blastocyst s from P4-treated delayed donors were transferred into the uteri of P4 -treated delayed pseudopregnant recipients at 1, 2, 4, or 8 h after an injection of 17 beta-estradiol (E2). Dormant blastocysts transferred into delayed recipients at 1 h after E2 treatment resulted in implanta tion in most of the animals as compared to complete failure of blastoc ysts to implant after transfer to P4-treated delayed recipients at 4 o r 8 h after E2 treatment. However, implantation did occur in P4-treate d delayed recipients at these later hours of E2 treatment when the P4- treated delayed donors also received E2 prior to blastocyst transfer. Furthermore, the majority of day 4 normal blastocysts implanted when t ransferred into P4-treated delayed recipients even at 16 h after E2 tr eatment. Interestingly, day 7 dormant blastocysts cultured for 8 or 24 h for in vitro activation failed to implant after transfer to P4-trea ted delayed pseudopregnant recipients at 4 or 8 h after E2 treatment, although they did implant after transfer at 1 h after E2 treatment. As expected, normal day 4 blastocysts failed to implant after transfer t o P4-treated delayed pseudopregnant recipients. Thus, these results es tablish that the blastocyst's state of activity alters the timing of i mplantation (window) in the receptive uterus. Thus, the window for suc cessful implantation could be defined as a limited time span when the activated stage of the blastocyst is superimposed on the receptive sta te of the uterus. This window remains open for a shorter period for do rmant blastocysts than for normal or dormant blastocysts after E2 acti vation. Furthermore, dormant blastocysts, which apparently achieved me tabolic activation in vitro, failed to attain the same status as blast ocysts activated in utero by E2 for implantation into the receptive ut erus. A key finding of this investigation is that E2 induces very rapi dly, but transiently (1 h), a factor(s) in the P4-primed uterus that a ctivates the dormant blastocysts for implantation in the receptive ute rus.