title: Contribution of G protein-coupled estrogen receptor 1 (GPER) to 17β-estradiol-induced developmental toxicity in zebrafish.
abstract: Exposure to 17β-estradiol (E2) influences the regulation of multiple signaling pathways, and E2-mediated disruption of signaling events during early development can lead to malformations such as cardiac defects. In this study, we investigated the potential role of the G-protein estrogen receptor 1 (GPER) in E2-induced developmental toxicity. Zebrafish embryos were exposed to E2 from 2h post fertilization (hpf) to 76 hpf with subsequent transcriptional measurements of heart and neural crest derivatives expressed 2 (hand2), leucine rich repeat containing 10 (lrrc10), and gper at 12, 28 and 76 hpf. Alteration in the expression of lrrc10, hand2 and gper was observed at 12 hpf and 76 hpf, but not at 28 hpf. Expression of these genes was also altered after exposure to G1 (a GPER agonist) at 76 hpf. Expression of lrrc10, hand2 and gper all coincided with the formation of cardiac edema at 76 hpf as well as other developmental abnormalities. While co-exposure of G1 with G36 (a GPER antagonist) rescued G1-induced abnormalities and altered gene expression, co-exposure of E2 with G36, or ICI 182,780 (an estrogen receptor antagonist) did not rescue E2-induced cardiac deformities or gene expression. In addition, no effects on the concentrations of downstream ER and GPER signaling molecules (cAMP or calcium) were observed in embryo homogenates after E2 treatment. These data suggest that the impacts of E2 on embryonic development at this stage are complex and may involve multiple receptor and/or signaling pathways.
authors.affiliation: Department of Environmental Sciences, University of California, Riverside, Riverside, CA 92507, United States. Electronic address: gdiam001@ucr.edu.
authors.forename: Graciel
authors.initials: G
authors.lastname: Diamante
authors.affiliation: Department of Environmental Sciences, University of California, Riverside, Riverside, CA 92507, United States.
authors.forename: Norma
authors.initials: N
authors.lastname: Menjivar-Cervantes
authors.affiliation: Department of Environmental Sciences, University of California, Riverside, Riverside, CA 92507, United States.
authors.forename: Man Sin
authors.initials: MS
authors.lastname: Leung
authors.affiliation: Department of Environmental Sciences, University of California, Riverside, Riverside, CA 92507, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Volz
authors.affiliation: Department of Environmental Sciences, University of California, Riverside, Riverside, CA 92507, United States. Electronic address: daniel.schlenk@ucr.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Schlenk
mesh_terms: D000818:Animals; D047108:Embryonic Development / Q000187:drug effects*; D004958:Estradiol / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000196:embryology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical / Q000633:toxicity; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; C549840:gper1 protein, zebrafish; D004958:Estradiol
keywords: 17β-Estradiol; Cardiac development; Endocrine system and estrogenic compounds; Zebrafish; gper