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Prenatal exposure to ethinylestradiol elicits behavioral abnormalities in the rat
M L Dugard1, H Tremblay-Leveau, D Mellier
1Laboratoire PSY.CO, U.F.R. de Psychologie, Université de Rouen, 76821 Mont-Saint-Aignan Cedex, France.
Insights
Prenatal exposure to 17alpha-ethinylestradiol in rats led to high neonatal death and significant adult behavioral abnormalities in survivors, suggesting developmental neurotoxicity.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Prenatal exposure to endocrine-disrupting chemicals can impact neurodevelopment.
- 17alpha-ethinylestradiol is a synthetic estrogen used in hormonal contraceptives.
Purpose of the Study:
- To investigate the long-term behavioral effects of prenatal exposure to 17alpha-ethinylestradiol on rat offspring.
- To assess potential alterations in cognitive and emotional processes due to gestational exposure.
Main Methods:
- Pregnant rats received daily intraperitoneal injections of 17alpha-ethinylestradiol or vehicle from day 9 to 14 of gestation.
- Offspring behavior was evaluated in adulthood, assessing motor activity, exploration, cognition, anxiety, and social interaction.
Main Results:
- A high percentage of neonatal death was observed in the prenatally exposed group.
- Surviving offspring exhibited increased spontaneous motor activity, reduced exploratory behavior, impaired cognition, and increased anxiety-like behavior and social neophobia.
- Behavioral alterations were consistent with disruptions in central nervous system ontogenesis affecting cognitive and emotional functions.
Conclusions:
- Gestational exposure to 17alpha-ethinylestradiol induces significant and lasting behavioral abnormalities in rat offspring.
- These findings suggest that ethinylestradiol can interfere with the developmental trajectory of brain regions crucial for behavior.
- The possibility of abnormal maternal behavior in treated dams as a confounding factor cannot be ruled out.
Abstract:
Pregnant rats were i.p. injected with a solution of 17alpha-ethinylestradiol (15 microg kg(-1)) every day between day 9 and day 14 of pregnancy and the behavior of the offspring was compared to that of rats born from dams injected with the vehicle only during the same gestational period. The percentage of neonatal death was dramatically high in the prenatally treated group. Growth of the surviving animals was even better than that of controls, but when adult, they exhibited a number of behavioral abnormalities: increased spontaneous motor activity, decreased exploratory behavior, impaired cognitive processing, qualitatively different exploratory drive, and/or persevering behavior, increased anxiety-like behavior and social neophobia. These behavioral alterations, which resemble a number of psychiatric syndromes, suggest that ethinylestradiol altered the ontogenesis of different parts of the central nervous system involved in cognitive and emotional processes. However, it cannot be excluded that the changes in behavior of ethinylestradiol exposed offspring were due to the abnormal maternal behavior of the estradiol treated dams.