Low-Dose Reproductive Effects Resulting From Prenatal Exposure to EstrogenEPA Grant Number: U914991
Title: Low-Dose Reproductive Effects Resulting From Prenatal Exposure to Estrogen
Investigators: Thayer, Kristina A.
Institution: University of Missouri - Columbia
EPA Project Officer: Lee, Sonja
Project Period: January 1, 1996 through January 1, 1999
Project Amount: $102,000
RFA: STAR Graduate Fellowships (1996) RFA Text | Recipients Lists
Research Category: Fellowship - Toxicology , Academic Fellowships , Health Effects
The overall objective of this research project was to provide information regarding the effects of prenatal exposure to low doses of estrogens. More specifically, in the first experiment, our objective was to examine the consequences for offspring resulting from maternal ingestion of clinically relevant doses of a synthetic estrogen found in many oral contraceptives (OCs), 17-ethinyl estradiol (EE2), because millions of women continue to take OCs while pregnant. In another experiment, we sought to characterize the response to maternal ingestion of the synthetic estrogen, diethylstilbestrol (DES), in offspring with three genotypes: mice lacking an allele (--) for estrogen receptor alpha (ERa), animals heterozygous for this mutation (+-), and wild-type (++) animals.
Our approach is to dose pregnant mice with synthetic estrogens during various critical periods in gestation, and examine the reproductive organs of the offspring at several times throughout life. Specifically, in the first experiment, pregnant mice were fed clinically relevant doses ranging from 0.002-2 mg/kg body weight (ppb) of EE2 on days 0-17 of pregnancy. The male offspring were examined at 2 and 5 months of age with regard to reproductive organ weights and daily sperm production. In the second experiment, pregnant dams heterozygous for a mutation in the ERa gene were fed doses ranging from 0.02-20 mg/kg DES on days 11-17 of pregnancy. The reproductive organs and daily sperm production were assessed in males at 6 months of age. Female offspring were ovariectomized and implanted with an estradiol capsule (5 mg/mouse) at 6 months of age, and the uterus was weighed.