Developmental and behavioral neurotoxicity of endocrine disrupting chemicals

Abstract

Endocrine disrupting chemicals (EDCs) are environmental contaminants that mimic or interfere with hormones. Many EDCs are estrogenic and may have the potential to cause alterations in reproduction or development at environmental exposure levels. The brain of rodents is extremely sensitive to estradiol and has long been a model for sexual differentiation. The hypothesis is that sexual differentiation of the rat brain is altered after exposure to EDCs during estrogen-sensitive periods of development and may be a model for studying mechanisms of action of EDCs. Prenatal exposure to 5 mg/kg of the estrogenic pesticide, chlordecone (CD), on day 16 of gestation altered sexually differentiated behaviors and brain morphology. Exposed female rats had decreased anxiety in the open field, and increased homotypic and heterotypic sex behaviors as compared to female controls. Exposed male rats had no change in activity levels in the open field or elevated plus maze, but had increased homotypic and heterotypic sex behaviors as compared to male controls. The volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA), a morphological measure of exposure to estrogen during development, was not different between CD-exposed and control adult animals of either gender. When SDN-POA volume was analyzed during the neonatal period, prenatal CD exposure increased SDN-POA volume in female rats at postnatal day (PN) 6-8. Increased incidence of pyknotic cells in the SDN-POA occurred at PN 8 and may explain the return to control values at PN 10. Prenatal exposure to 5 mug/kg of the synthetic estrogen diethylstilbestrol (DES), caused a similar increase in SDN volume at PN 6, but not at PN 12 or 18, and exposure to 5 mg/kg bisphenol A (BPA), a weak estrogen in plastics, did not alter SDN-POA volume. In conclusion, prenatal exposure to relatively low doses of some EDCs altered the function and development of the brain in male and female rats. Changes in the SDN-POA volume occurred in females only during the neonatal period and were associated with changes in cell death. The transient effects detected in the SDN-POA suggest that developmental changes may have occurred in brain regions involved in adult behavior.