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The present study examined the effects of progesterone (P) and 17β-estradiol (E2) on fetal damage and intrauterine pressure in ovariectomized pregnant mice. The mice were ovariectomized on gestational day (GD) 9 (copulation plug = GD 0), and daily subcutaneous injection of various doses of P (2, 3 or 4 mg) or 4 mg P plus E2 (0.05 or 0.1 μg) was given thereafter. Although P alone increased percentage of normal fetuses on GD 17 dose-dependently, fetal injury with edematous hematomata on their extremities was frequently observed. In the group treated with 4 mg P, the injured fetus was found at the highest percentage (18%) and intrauterine pressure was significantly higher than that in intact pregnant mice (controls). No injured fetus on GD 17 was found by the treatment with 4 mg P plus 0.05 or 0.1 μg E2, and the treatments decreased the intrauterine pressure to the level of controls. Percentage of normal fetuses in the ovariectomized mice treated with 4 mg P plus 0.05 μg E2 was similar to that of controls, while that in the ovariectomized mice treated with 4 mg P plus 0.1 μg E2 markedly decreased. The results suggest that estrogen decreases intrauterine pressure to defend fetal damage in ovariectomized P-treated mice, and a high estrogen level interrupted pregnancy while keeping this estrogen action.

Rescue of the fetal damage associated with high intrauterine pressure by 17β-estradiol injection in ovariectomized progesterone-treated pregnant mice