Exposure of neonatal female rats to bisphenol A disrupts hypothalamic LHRH pre-mRNA processing and estrogen receptor alpha expression in nuclei controlling estrous cyclicity

This study examines the effects of neonatal exposure to the endocrine disruptor bisphenol A (BPA) on the neural network that controls estrous cyclicity From postnatal day 1 (PND1) to PND7 female pups were injected with vehicle (control) or BPA (BPA 05 0 05 mg/kg-d BPA20 20 mg/kg-d) At PND100 BPA.05-females showed alterations in estrous cyclicity and BPA20-females were Incapable of producing an estradiol-induced LH surge By real-time PCR we determined that hypothalamic expression of mature LH-releasing hormone (LHRH) mRNA was increased in BPA 05 and decreased in BPA20-females Furthermore unprocessed intron A-containing LHRH RNA was decreased in the cytoplasm of hypothalamic cells of both groups Immunohistochemistry revealed that estrogen receptor alpha protein was up-regulated in anteroventral periventricular and down-regulated in arcuate nucleus of both groups Our results show that BPA permanently disrupts hypothalamic LHRH pre-mRNA processing and steroid receptors expression in nuclei that control estrous cyclicity in adult rats (C) 2010 Elsevier Inc All rights reserved