Embryo survival, and fetal and placental growth following elevation of maternal estradiol blood concentrations in the rat.

Abstract

High doses of estrogens cause embryonic mortality, and fetal and placental growth retardation in rats. This study addresses the physiological relevance of such findings. Estradiol benzoate (EB), by s.c. injection, or estradiol-17beta (E2), delivered by a miniosmotic pump, raised maternal E2 concentrations from only slightly above control values to 5-fold. EB (1 microgram/day) over Days 6-13, 8-13, and 11-13, and continuous infusion of E2 (15 ng/h; Days 10-13) reduced fetal survival to 0%, 0%, 22%, and 75%, respectively. Single injections of EB showed that its lethal effect declined rapidly over Days 9 (44% survival) to 13 (90% survival). Embryos died within 48 h, but death was not due to luteal failure since progesterone levels were maintained and progesterone administered with EB did not reduce mortality. Administration of EB at 1 microgram/day (Days 14-21) or E2 at 40 ng/h (Days 13-16) retarded fetal and placental growth but did not affect survival. The rat embryo is highly sensitive to elevated maternal estradiol concentrations over much of gestation. The early lethal effect implies that endogenous E2 production is carefully regulated to maintain pregnancy; the latter growth-retarding effect suggests that E2 may have a role in the normal control of fetal growth.