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: 0.05mg/kg-d, BPA20: 20mg/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.
Laboratorio de Endocrinología y Tumores Hormonodependientes, School of Biochemistry and Biological Sciences, Universidad Nacional del Litoral, Santa Fe, Argentina.
L
L
Monje
J
J
Varayoud
M
M
Muñoz-de-Toro
E H
EH
Luque
J G
JG
Ramos
D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D030762:Estrous Cycle / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007438:Introns; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D012322:RNA Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D009419:Nerve Tissue Proteins; D010636:Phenols; D012322:RNA Precursors; D012333:RNA, Messenger; C006780:bisphenol A; D000098826:Bisphenol A Compounds