title: Sexually dimorphic effects of gestational endocrine-disrupting chemicals on microRNA expression in the developing rat hypothalamus.
abstract: This study examined developmental changes and sexual dimorphisms in hypothalamic microRNAs, and whether gestational exposures to environmental endocrine-disrupting chemicals (EDCs) altered their expression patterns. Pregnant rat dams were treated on gestational days 16 and 18 with vehicle, estradiol benzoate, or a mixture of polychlorinated biphenyls. Male and female offspring were euthanized on postnatal days (P) 15, 30, 45, or 90, and microRNA and mRNA targets were quantified in the medial preoptic nucleus (MPN) and ventromedial nucleus (VMN) of the hypothalamus. MicroRNAs showed robust developmental changes in both regions, and were sexually dimorphic in the MPN, but not VMN. Importantly, microRNAs in females were up-regulated by EDCs at P30, and down-regulated in males at P90. Few changes in mRNAs were found. Thus, hypothalamic microRNAs are sensitive to prenatal EDC treatment in a sex-, developmental age-, and brain region-specific manner.
authors.affiliation: Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Viktoria Y
authors.initials: VY
authors.lastname: Topper
authors.affiliation: Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Deena M
authors.initials: DM
authors.lastname: Walker
authors.affiliation: Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA; Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA; Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: andrea.gore@austin.utexas.edu.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Gore
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004785:Environmental Pollutants / Q000008:administration & dosage* / Q000494:pharmacology; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D035683:MicroRNAs / Q000187:drug effects / Q000235:genetics*; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage* / Q000494:pharmacology; D011247:Pregnancy; D011301:Preoptic Area / Q000254:growth & development / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D051381:Rats; D012727:Sex Characteristics; D014697:Ventromedial Hypothalamic Nucleus / Q000254:growth & development* / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D035683:MicroRNAs; D012333:RNA, Messenger; C074283:estradiol 3-benzoate; D004958:Estradiol; D011078:Polychlorinated Biphenyls
keywords: Endocrine-disrupting chemicals (EDCs); Hypothalamus; Medial preoptic nucleus (MPN); MicroRNA; Polychlorinated biphenyls (PCBs); Ventromedial nucleus (VMN)