Implantation of the rabbit blastocyst: sequential changes in estradiol and progesterone and their receptors

To determine the temporal relationship of the endocrine events involved in rabbit blastocyst implantation, (1) progesterone (P) and estradiol (E) in plasma and uterine flushings, (2) P and E in the cytosol of endometrium and myometrium, and (3) P receptors (PR) and E receptors (ER) in endometrium and myometrium were examined from days 0 through 7 post coitum by radioimmunoassay and radioreceptorassay. Plasma P levels increased significantly from 0.3 +/- 0.06 to 76 +/- 9.4 ng/ml (p = less than 0.005) 2 hours after mating (day 0), declined to 10.0 +/- 1.2 ng/ml by day 6, and increased to 12.0 +/- 1.2 ng/ml by day 7. Cytosol P levels of endometrium and myometrium increased from 3.2 +/- 0.2 to 22.8 +/- 2.2 ng/gm and 2.1 +/- 0.4 to 14.1 +/- 2.1, respectively, from days 1 to 6. On day 7, cytosol P levels of the embryonic segment (8.2 +/- 0.5 ng/gm) were lower than those of the interembryonic segment (12.4 +/- 1.8 ng/gm). P levels in uterine flushings increased significantly from 0.05 +/- 0.01 ng/ml on day 0 to 19.9 +/- 0.7 ng/ml on day 7 (p = less than 0.001). In contrast, E levels in plasma, uterine flushings, and cytosol of uterine tissues showed no significant change from days 1 through 7, but the levels from 6 hours after mating were significantly higher than those before mating (p = less than 0.05). ER in the cytosol and nucleus of all uterine regions increased significantly after mating but decreased after implantation. In contrast, PR in the cytosol and nucleus of all uterine regions showed no significant change on days 0 to 6 post coitum. After implantation, the embryonic segment had significantly higher PR in the nucleus than that in the cytosol (13.0 +/- 1.5 versus 8.0 +/- 0.5 fmol/micrograms), whereas the interembryonic segment had significantly higher PR in the cytosol than that in the nucleus (12.0 +/- 0.5 versus 9.0 +/- 0.5 fmol/micrograms DNA). These findings showed that changes in P in the plasma and uterine flushings preceded those in uterine tissues before implantation. The changes in uterine tissue ER and PR after mating but before and after implantation suggest that the putative nidatory sites are prepared for implantation but undergo endocrine changes to protect the conceptus immediately after implantation.