Regulation of arcuate genes by developmental exposures to endocrine-disrupting compounds in female rats

Reprod Toxicol. 2016 Jul:62:18-26. doi: 10.1016/j.reprotox.2016.04.014. Epub 2016 Apr 19.

Abstract

Developmental exposure to endocrine-disrupting compounds (EDCs) alters reproduction and energy homeostasis, both of which are regulated by the arcuate nucleus (ARC). Little is known about the effects of EDC on ARC gene expression. In Experiment #1, pregnant dams were treated with either two doses of bisphenol A (BPA) or oil from embryonic day (E)18-21. Neonates were injected from postnatal day (PND)0-7. Vaginal opening, body weights, and ARC gene expression were measured. Chrm3 (muscarinic receptor 3) and Adipor1 (adiponectin receptor 1) were decreased by BPA. Bdnf (brain-derived neurotropic factor), Igf1 (insulin-like growth factor 1), Htr2c (5-hydroxytryptamine receptor), and Cck2r (cholescystokinin 2 receptor) were impacted. In Experiment #2, females were exposed to BPA, diethylstilbestrol (DES), di(2-ethylhexyl)phthalate, or methoxychlor (MXC) during E11-PND7. MXC and DES advanced the age of vaginal opening and ARC gene expression was impacted. These data indicate that EDCs alter ARC genes involved in reproduction and energy homeostasis in females.

Keywords: Arcuate nucleus; Bisphenol a; Diethylstilbestrol; Endocrine-disrupting compounds; Energy homeostasis; Methoxychlor; Phthalates; Puberty.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Benzhydryl Compounds / toxicity
  • Brain-Derived Neurotrophic Factor / genetics
  • Diethylhexyl Phthalate / toxicity
  • Diethylstilbestrol / toxicity
  • Endocrine Disruptors / toxicity*
  • Female
  • Gene Expression Regulation, Developmental / drug effects*
  • Homeostasis / drug effects
  • Insulin-Like Growth Factor I / genetics
  • Methoxychlor / toxicity
  • Phenols / toxicity
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats, Inbred F344
  • Receptor, Cholecystokinin B / genetics
  • Receptor, Muscarinic M3 / genetics
  • Receptor, Serotonin, 5-HT2C / genetics
  • Receptors, Adiponectin / genetics
  • Sexual Maturation / drug effects

Substances

  • Benzhydryl Compounds
  • Brain-Derived Neurotrophic Factor
  • Endocrine Disruptors
  • Phenols
  • Receptor, Cholecystokinin B
  • Receptor, Muscarinic M3
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Adiponectin
  • adiponectin receptor 1, rat
  • insulin-like growth factor-1, rat
  • Insulin-Like Growth Factor I
  • Diethylstilbestrol
  • Diethylhexyl Phthalate
  • bisphenol A
  • Methoxychlor