title: Hypothalamic transcriptomic alterations in male and female California mice (Peromyscus californicus) developmentally exposed to bisphenol A or ethinyl estradiol.
abstract: Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) prevalent in many household items. Rodent models and human epidemiological studies have linked this chemical to neurobehavior impairments. In California mice, developmental exposure to BPA results in sociosexual disorders at adulthood, including communication and biparental care deficits, behaviors that are primarily regulated by the hypothalamus. Thus, we sought to examine the transcriptomic profile in this brain region of juvenile male and female California mice offspring exposed from periconception through lactation to BPA or ethinyl estradiol (EE, estrogen present in birth control pills and considered a positive estrogen control for BPA studies). Two weeks prior to breeding, P0females were fed a control diet, or this diet supplemented with 50 mg BPA/kg feed weight or 0.1 ppb EE, and continued on the diets through lactation. At weaning, brains from male and female offspring were collected, hypothalamic RNA isolated, and RNA-seq analysis performed. Results indicate that BPA and EE groups clustered separately from controls with BPA and EE exposure leading to unique set of signature gene profiles.Kcnd3was downregulated in the hypothalamus of BPA- and EE-exposed females, whereasTbl2,Topors,Kif3a, andPhactr2were upregulated in these groups. Comparison of transcripts differentially expressed in BPA and EE groups revealed significant enrichment of gene ontology terms associated with microtubule-based processes. Current results show that perinatal exposure to BPA or EE can result in several transcriptomic alterations, including those associated with microtubule functions, in the hypothalamus of California mice. It remains to be determined whether these genes mediate BPA-induced behavioral disruptions.
authors.affiliation: Bond Life Sciences Center, University of Missouri, Columbia, Missouri.|Biomedical Sciences, University of Missouri, Columbia, Missouri.|Animal Sciences, University of Missouri, Columbia, Missouri.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Johnson
authors.affiliation: Bond Life Sciences Center, University of Missouri, Columbia, Missouri.|Informatics Research Core Facility University of Missouri, Columbia, Missouri.
authors.forename: William G
authors.initials: WG
authors.lastname: Spollen
authors.affiliation: Bond Life Sciences Center, University of Missouri, Columbia, Missouri.|Biomedical Sciences, University of Missouri, Columbia, Missouri.
authors.forename: Lindsey K
authors.initials: LK
authors.lastname: Manshack
authors.affiliation: DNA Core Facility, University of Missouri, Columbia, Missouri.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Bivens
authors.affiliation: Bond Life Sciences Center, University of Missouri, Columbia, Missouri givans@missouri.edu rosenfeldc@missouri.edu.|Informatics Research Core Facility University of Missouri, Columbia, Missouri.|Molecular Microbiology and Immunology, University of Missouri, Columbia, Missouri.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Givan
authors.affiliation: Bond Life Sciences Center, University of Missouri, Columbia, Missouri givans@missouri.edu rosenfeldc@missouri.edu.|Biomedical Sciences, University of Missouri, Columbia, Missouri.|Genetics Area Program, University of Missouri, Columbia, Missouri.|Thompson Center for Autism and Neurobehavioral Disorders, University of Missouri, Columbia, Missouri.
authors.forename: Cheryl S
authors.initials: CS
authors.lastname: Rosenfeld
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D015536:Down-Regulation; D052244:Endocrine Disruptors / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D018811:Maternal Exposure; D010542:Peromyscus; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism*; D059467:Transcriptome / Q000187:drug effects*; D015854:Up-Regulation; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004997:Ethinyl Estradiol; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Brain; DOHaD; RNA‐seq; endocrine‐disrupting chemicals; estrogens