title: Effects of di-(2-ethylhexyl) phthalate and four of its metabolites on steroidogenesis in MA-10 cells.
abstract: Phthalate plasticizers are used in the plastics industry to aid in processing and impart flexibility to plastics. Due to the broad use of plastics, and the tendency of plasticizers to leach out of polymers, plasticizers have become ubiquitous in the environment. Concerns about the testicular toxicity of phthalate plasticizers, in particular di-(2-ethylhexyl) phthalate (DEHP), have arisen due to their ability to cause male reproductive tract abnormalities in animal models. It has been assumed that the DEHP metabolite, mono-(2-ethylhexyl) phthalate (MEHP), is the active compound, however, metabolites such as 2-ethylhexanol, 2-ethylhexanal and 2-ethylhexanoic acid, have not been thoroughly investigated. The aim of this study was to evaluate the anti-androgenic potential of these metabolites in vitro with a mouse Leydig tumor cell line, MA-10 cells. DEHP, MEHP and 2-ethylhexanal were found to decrease cell viability, as well as steroidogenic potential. The latter was assessed using an enzyme-linked immunosorbent assay (ELISA) to quantify steroid production and quantitative real-time polymerase chain reaction (qRT-PCR) to assess gene expression analysis of key steroidogenic enzymes. 2-Ethylhexanal proved to be the most potent steroidogenic disruptor, offering intriguing implications in the search for the mechanism of phthalate testicular toxicity. Overall, the study suggests the involvement of multiple active metabolites in the testicular toxicity of DEHP.
authors.affiliation: Department of Chemical Engineering, McGill University, 3610 University Street, Montréal, QC, Canada H3A 2B2.
authors.forename: Carlie D
authors.initials: CD
authors.lastname: Piché
authors.affiliation: Department of Chemical Engineering, McGill University, 3610 University Street, Montréal, QC, Canada H3A 2B2; Department of Chemical and Materials Engineering, University of Alberta, 9107 116 Sreet, Edmonton, AB, Canada T6G 2V4.
authors.forename: Dominic
authors.initials: D
authors.lastname: Sauvageau
authors.affiliation: Department of Chemical Engineering, McGill University, 3610 University Street, Montréal, QC, Canada H3A 2B2.
authors.forename: Marie
authors.initials: M
authors.lastname: Vanlian
authors.affiliation: Department of Chemical Engineering, McGill University, 3610 University Street, Montréal, QC, Canada H3A 2B2.
authors.forename: Hanno C
authors.initials: HC
authors.lastname: Erythropel
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montréal, QC, Canada H3G 1Y6.
authors.forename: Bernard
authors.initials: B
authors.lastname: Robaire
authors.affiliation: Department of Chemical Engineering, McGill University, 3610 University Street, Montréal, QC, Canada H3A 2B2. Electronic address: richard.leask@mcgill.ca.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Leask
mesh_terms: D000447:Aldehydes / Q000633:toxicity; D000818:Animals; D002208:Caproates / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D000441:Hexanols / Q000633:toxicity; D007984:Leydig Cell Tumor / Q000378:metabolism; D008297:Male; D051379:Mice; D010968:Plasticizers / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D013256:Steroids / Q000502:physiology
chemical_list: D000447:Aldehydes; D002208:Caproates; D052244:Endocrine Disruptors; D000441:Hexanols; D010968:Plasticizers; D013256:Steroids; C040668:2-ethylhexanoic acid; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate; C040669:2-ethylhexanal; C034017:2-ethylhexanol