title: Phthalate esters affect maturation and function of primate testis tissue ectopically grafted in mice.
abstract: Di-n-Butyl (DBP) and Di-(2-EthylHexyl) (DEHP) phthalates can leach from daily-use products resulting in environmental exposure. In male rodents, phthalate exposure results in reproductive effects. To evaluate effects on the immature primate testis, testis fragments from 6-month-old rhesus macaques were grafted subcutaneously to immune-deficient mice, which were exposed to 0, 10, or 500 mg/kg of DBP or DEHP for 14 weeks or 28 weeks (DBP only). DBP exposure reduced the expression of key steroidogenic genes, indicating that Leydig cell function was compromised. Exposure to 500 mg/kg impaired tubule formation and germ cell differentiation and reduced numbers of spermatogonia. Exposure to 10 mg/kg did not affect development, but reduced Sertoli cell number and resulted in increased expression of inhibin B. Exposure to DEHP for 14 week also affected steroidogenic genes expression. Therefore, long-term exposure to phthalate esters affected development and function of the primate testis in a time and dosage dependent manner.
authors.affiliation: Department of Comparative Biology & Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348, United States.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Rodriguez-Sosa
authors.affiliation: Department of Comparative Biology & Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Alla
authors.initials: A
authors.lastname: Bondareva
authors.affiliation: Department of Comparative Biology & Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Lin
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Gleide F
authors.initials: GF
authors.lastname: Avelar
authors.affiliation: Department of Comparative Biology & Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Krysta M
authors.initials: KM
authors.lastname: Coyle
authors.affiliation: Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Modelski
authors.affiliation: Department of Comparative Biology & Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Whitney
authors.initials: W
authors.lastname: Alpaugh
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, United States.
authors.forename: Alan
authors.initials: A
authors.lastname: Conley
authors.affiliation: Department of Comparative Biology & Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Katherine
authors.initials: K
authors.lastname: Wynne-Edwards
authors.affiliation: Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Luiz R
authors.initials: LR
authors.lastname: França
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, United States.
authors.forename: Stuart
authors.initials: S
authors.lastname: Meyers
authors.affiliation: Department of Comparative Biology & Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348, United States. Electronic address: idobrins@ucalgary.ca.
authors.forename: Ina
authors.initials: I
authors.lastname: Dobrinski
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003993:Dibutyl Phthalate / Q000009:adverse effects* / Q000494:pharmacology; D004051:Diethylhexyl Phthalate / Q000009:adverse effects* / Q000494:pharmacology; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005854:Germ Cells / Q000166:cytology; D007265:Inhibins / Q000096:biosynthesis; D007985:Leydig Cells / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012671:Seminiferous Tubules / Q000196:embryology; D012708:Sertoli Cells / Q000166:cytology; D013093:Spermatogonia / Q000166:cytology; D013737:Testis / Q000254:growth & development* / Q000637:transplantation*; D014183:Transplantation, Heterologous
chemical_list: C422364:inhibin B; D003993:Dibutyl Phthalate; D007265:Inhibins; D004051:Diethylhexyl Phthalate
keywords: Non-human primates; Phthalates; Spermatogenesis; Steroidogenesis; Testis; Testis development