title: Male rats exposed in utero to di(n-butyl) phthalate: Age-related changes in Leydig cell smooth endoplasmic reticulum and testicular testosterone-biosynthesis enzymes/proteins.
abstract: This study investigated the age-related (i.e., weeks 5, 7, 9, 14 and 17) morphological changes of Leydig cell smooth endoplasmic reticulum (LCs-ER) and testicular testosterone biosynthesis/protein expression in rats in utero exposed to di(n-butyl) phthalate (DBP) (intragastrically; 100mg/kg/day) on days 12-21 post-conception. Ultrastructural observations revealed the LCs-ER of the DBP group were non-dilated until peri-puberty, and thereafter decreased and disappeared. RT-PCR and Western blotting analyses revealed that StAR and P450scc levels in the DBP group were significantly lower at 5 and 7 weeks compared with the vehicle group but became similar during weeks 9-17. Although 3β-HSD, P450c17, and 17β-HSD levels of mRNA and protein in the DBP group were similar to the vehicle control group at 5 and 7 weeks of age, they were significantly lower during weeks 9-17. In utero DBP exposure results in age-related LCs-ER changes corresponding to reduction of testicular testosterone biosynthesis enzymes/associated proteins.
authors.affiliation: Department of Toxicology, Laboratory Animal Science, Veterinary Anatomy, Animal Breeding, and Genetics, Azabu University School of Veterinary Medicine, Kanagawa, Japan. Electronic address: qv1128@azabu-u.ac.jp.
authors.forename: Masaya
authors.initials: M
authors.lastname: Motohashi
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Wempe
authors.affiliation: Toxicology and Pathology Res, SRICC, Sapporo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mutou
authors.affiliation: Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Toxicology, Laboratory Animal Science, Veterinary Anatomy, Animal Breeding, and Genetics, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Kansaku
authors.affiliation: Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikegami
authors.affiliation: Department of Toxicology, Laboratory Animal Science, Veterinary Anatomy, Animal Breeding, and Genetics, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
authors.forename: Tomo
authors.initials: T
authors.lastname: Inomata
authors.affiliation: Department of Toxicology, Laboratory Animal Science, Veterinary Anatomy, Animal Breeding, and Genetics, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Asari
authors.affiliation: Department of Toxicology, Laboratory Animal Science, Veterinary Anatomy, Animal Breeding, and Genetics, Azabu University School of Veterinary Medicine, Kanagawa, Japan; Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: wakui@azabu-u.ac.jp.
authors.forename: Shin
authors.initials: S
authors.lastname: Wakui
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D048430:Cell Shape / Q000187:drug effects; D003993:Dibutyl Phthalate / Q000633:toxicity*; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*
chemical_list: D012333:RNA, Messenger; D003993:Dibutyl Phthalate; D013739:Testosterone; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; C582555:CYP17A1 protein, rat; D013254:Steroid 17-alpha-Hydroxylase
keywords: 17β-HSD; 3β-HSD; In utero DBP exposure; Leydig cell sER; P450c17; P450scc; Rat; StAR