Abstract
Although perinatal exposure of female rats to estrogenic compounds produces irreversible changes in brain function, it is still unclear how the amount and timing of exposure to those substances affect learning function, or if exposure alters estrogen receptor α (ERα) expression in the hippocampus and cortex. In adult female rats, we investigated the effects of neonatal exposure to a model estrogenic compound, ethinyl estradiol (EE), on passive avoidance learning and ERα expression. Female Wistar-Imamichi rats were subcutaneously injected with oil, 0.02 mg/kg EE, 2 mg/kg EE, or 20 mg/kg 17β-estradiol within 24 h after birth. All females were tested for passive avoidance learning at the age of 6 weeks. Neonatal 0.02 mg/kg EE administration significantly disrupted passive avoidance compared with oil treatment in gonadally intact females. In a second experiment, another set of experimental females, treated as described above, was ovariectomized under pentobarbital anesthesia at 10 weeks of age. At 15–17 weeks of age, half of each group received a subcutaneous injection of 5 μg estradiol benzoate a day before the passive avoidance learning test. Passive avoidance learning behavior was impaired by the 0.02 mg/kg EE dose, but notably only in the estradiol benzoate-injected group. At 17–19 weeks of age, hippocampal and cortical samples were collected from rats with or without the 5 μg estradiol benzoate injection, and western blots used to determine ERα expression. A significant decrease in ERα expression was observed in the hippocampus of the estradiol-injected, neonatal EE-treated females. The results demonstrated that exposure to EE immediately after birth decreased learning ability in adult female rats, and that this may be at least partly mediated by the decreased expression of ERα in the hippocampus.
Highlights
Xenoestrogens are compounds in the environment that mimic the physiologic activity of estrogen; they are contained in industrial contaminants, plastics or plasticizers, pesticides, and certain plants [1,2]
The results of this study show that a single exposure to 0.02 mg/kg of ethinyl estradiol (EE) within 24 h after birth lowered performance in the passive avoidance learning test
This study reveals a tendency towards shorter latencies to enter the shock compartment in the passive avoidance learning test of the LEE OVX group that received estradiol benzoate (EB) after maturation as a normal/fertile female model
Summary
Xenoestrogens are compounds in the environment that mimic the physiologic activity of estrogen; they are contained in industrial contaminants, plastics or plasticizers, pesticides, and certain plants [1,2]. Exposure to such estrogenic substances can have a profound adverse influence on the development of the nervous system in both animals and humans. One such influence is the impairment of learning and memory [4,5,6,7,8,9]. The female offspring of Wistar rat dams exposed during pregnancy and lactation to bisphenol A (BPA), an estrogenic agent in polycarbonate plastics, demonstrated impaired learning in step-down passive avoidance tasks as adults [6]. The female progeny of dams exposed from gestation to lactation to the estrogenic agent isobutylparaben, a widely used preservative, demonstrated poor social recognition performance [7]. The heavy metal pollutant cadmium can mimic estrogens [10], such that cadmium toxicity can inhibit avoidance acquisition in female offspring [9]
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