Summary.A suitable hormonal environment is a prerequisite for blastocyst implantation. Experimental diabetes was previously shown to modify the hormonal milieu and produce alterations in oestrogen receptor kinetics in the uterine tissue. In the present work, oestrogen and progestogen receptor levels were measured on the morning of day 6 of pregnancy in normal and in streptozotocin-induced diabetic rats, both in implantation sites and in interembryonic segments of endometrium and myometrium. Receptor levels were different in the implantation sites compared to the interembryonic segments of endometrium, both in the control and in the diabetic animals. Indeed, implantation sites were characterized by lower oestrogen receptor levels in cytosol and higher progestogen receptor levels in cytosol and nuclei. However, compared to the control rats, the diabetic rats had lower oestrogen receptor levels in implantation sites, both in cytosol and nuclei. In the myometrium, the differences between sites or between types of rats were minimal. Plasma levels of oestradiol were lower in diabetic rats than in control animals, whereas progesterone levels were similar. A 20% lower implantation rate was found in diabetic rats, compared to normal rats. These results show that the specific distribution of oestrogen and progestogen receptors between implantation sites and interembryonic segments was preserved in the diabetic rats; however the absolute level of oestrogen receptor was lower. This abnormal endocrine milieu might arise from a lower oestradiol level and a decreased oestradiol/progesterone ratio in the circulating blood. Whether the lower implantation rate in diabetic rats might be a consequence of the overall disturbed hormonal status remains to be elucidated.

Estrogens play a central role in the mechanism of blastocyst implantation. Whether the blastocyst itself contributes to this hormonal effect by locally releasing estrogens at the site of implantation remains debatable. Indirect evidence of estrogen production by the embryo could be obtained if specific estrogenic effects were found to a greater extent at the implantation sites, when compared to the interembryonic segments. Six-day pregnant rats were injected in the morning with Evans' blue, and the uterine blue stripes revealing the implantation sites were separated from the interembryonic segments. Endometrial and myometrial portions of the two sites were separately pooled and analyzed for protein, estradiol receptor (E2R) and progesterone receptor (Prog.R) contents, in cytosol and nuclear fractions. The present results show a significantly higher protein concentration in cytosol of endometrium (20 +/- 6.2 vs. 12 +/- 7.6) (means +/- SD) and, to a lesser extent, in the cytosol of myometrium (10 +/- 2.5 vs. 8.1 +/- 2.2 mg/mg DNA) at the implantation sites as compared to interembryonic segments. Protein levels were slightly higher in nuclei of endometrium only (8.3 +/- 3.4 vs. 6.4 +/- 4.5 mg/mg DNA). E2R concentrations were significantly lower in cytosol of endometrium from implantation sites (3.5 +/- 1.4 vs. 5.0 +/- 2.6 pmol/mg DNA), whereas nuclear levels were higher (0.63 +/- 0.38 vs. 0.47 +/- 0.24 pmol/mg DNA); nuclei-cytosol ratios were significantly higher in endometrium from implantation sites (16 +/- 7 vs. 9.7 +/- 5%). In myometrium no differences were observed between the two sites. Prog.R were higher both in cytosol (3.3 +/- 1.0 vs. 2.0 +/- 0.3) and in nuclei (3.0 +/- 1.2 vs. 1.4 +/- 0.7 pmol/mg DNA) of endometrium from implantation sites; nuclei-cytosol ratios were also higher (97 +/- 32 vs. 71 +/- 34%). In myometrium, differences between the sites were minimal. Our results show higher protein concentration in endometrium from implantation sites, mostly in cytosol and to a lesser extent in nuclei; lower cytosol but higher nuclear E2R concentrations, and both higher cytosol and nuclear Prog.R concentrations in endometrium from implantations sites, and strongly suggest a local estrogenic effect on tissues in close vicinity of the blastocyst. Thus they favor the hypothesis of estrogen release by the embryo itself.

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