title: Disposition of glycolic acid into rat and rabbit embryos in vitro.
abstract: High dose gavage administration of ethylene glycol (EG) induces teratogenicity in rodents, but not in rabbits, resulting from saturation of intermediate EG metabolism and glycolic acid (GA) accumulation. In vivo, rat embryos sequester GA 2-4-fold higher than maternal blood, a phenomenon absent in rabbits and proposed not to occur in humans. This research explored the mechanisms of GA disposition into rat and rabbit conceptuses using whole embryo culture (WEC). Rat and rabbit embryos concentrated GA from the culture medium. In vitro to in vivo discordance in the rabbit plausibly stemmed from anatomical differences between these models. GA sequestration was attenuated at 4°C in both species. Rat embryos further demonstrated pH-dependence of GA sequestration and inhibition by D-lactic acid. These data suggest GA disposition into rat and rabbit embryos is energy- and pH-dependent, and carrier-mediated. Anatomical and maternal-to-conceptal pH gradient differences likely underlie the lack of enhanced GA disposition in non-rodent species.
authors.affiliation: Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland 48674, USA. Electronic address: rellis-hutchings@dow.com.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ellis-Hutchings
authors.affiliation: Toxicology and Environmental Research and Consulting, Dow Europe GmbH, Horgen, Switzerland.
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Moore
authors.affiliation: Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland 48674, USA.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Marshall
authors.affiliation: Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland 48674, USA.
authors.forename: Reza J
authors.initials: RJ
authors.lastname: Rasoulpour
authors.affiliation: Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland 48674, USA.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Carney
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D046149:Embryo Culture Techniques; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D006016:Glycolates / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000378:metabolism; D011247:Pregnancy; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature
chemical_list: D006016:Glycolates; D011506:Proteins; C031149:glycolic acid; D019344:Lactic Acid
keywords: Ethylene glycol; Glycolic acid; Ion trapping; Rabbit; Rat; Sequestration; Whole embryo culture