title: Effect of methylmercury on glutamate-cysteine ligase expression in the placenta and yolk sac during mouse development.
abstract: The placenta and the yolk sac play critical roles in fetal development, including protection from oxidative stress through the presence of detoxifying enzymes. Glutathione (GSH; gamma-glutamylcysteinylglycine), a crucial molecule in the maintenance of cellular redox status, plays a critical role in development, and it is also protective against methylmercury toxicity. Glutamate-cysteine ligase (GCL), the enzyme that catalyzes the rate-limiting step in GSH synthesis, is widely expressed in the mouse embryo and extraembryonic membranes throughout development. The aim of this study was to investigate the effect of low-level subchronic methylmercury exposure on GCL expression in the mouse placenta and yolk sac, after describing the basal developmental expression of the enzyme in these tissues. We found that basal mRNA expression levels increased dramatically in the placenta and the yolk sac at gd 18, whereas protein levels did not increase in parallel with the mRNA. We also found that methylmercury induced GCLc mRNA expression in the placenta at gd 18 in a dose-dependent manner, suggesting an important role for this enzyme in the response of the placenta to toxicants. These changes in expression may be useful as a biomarker of MeHg exposure during development.
authors.affiliation: Department of Environmental Health, University of Washington, Mail Box 354695, 4225 Roosevelt Way NE, Seattle, WA 98195, USA.
authors.forename: Dolores
authors.initials: D
authors.lastname: Díaz
authors.forename: Cecile M
authors.initials: CM
authors.lastname: Krejsa
authors.forename: Collin C
authors.initials: CC
authors.lastname: White
authors.forename: Jay S
authors.initials: JS
authors.lastname: Charleston
authors.forename: Terrance J
authors.initials: TJ
authors.lastname: Kavanagh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis* / Q000235:genetics; D017403:In Situ Hybridization; D008297:Male; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014881:Water Supply; D015017:Yolk Sac / Q000187:drug effects* / Q000201:enzymology
chemical_list: D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D012333:RNA, Messenger; D005721:Glutamate-Cysteine Ligase