title: In utero-exposed di(n-butyl) phthalate induce dose dependent, age-related changes of morphology and testosterone-biosynthesis enzymes/associated proteins of Leydig cell mitochondria in rats.
abstract: Female pregnant Sprague-Dawley rats were intragastrically (ig) administered di(n-butyl) phthalate (DBP) at four doses (0, 10, 50 and 100 mg/kg) during gestation days (GD) 12-21 (n = 5 per group). The age-related morphological changes of Leydig cell mitochondrion (LC-Mt) and testosterone biosynthesis enzymes/associated genes/proteins expression levels were investigated. As compared to the control (no DBP), the 10 mg, and 50 mg DBP dose groups, the 100 mg DBP dose group at weeks 5 and 7 showed a significant amount of small LC-Mt. Thereafter, from weeks 9 to 17, the LC-Mt size and quantity in the 100 mg DBP dose group increased and became statistically similar to the other dose groups; hence, dose and time-dependent LC-Mt changes were observed. Throughout the study, the 100 mg DBP dose group had significantly lower testosterone levels. In addition, the 100 mg DBP dose group displayed lower StAR (StAR, steroidogenic acute regulatory protein) and P450scc (CYP11a1, cholesterol side-chain cleavage enzyme) levels at weeks 5 and 7, but they became statistically similar to all other dose groups at weeks 9 to 17; in contrast, the SR-B1 (Sarb1, scavenger receptor class B member 1) levels were similar for all DBP dose groups. The rats in utero 100 mg DBP /kg/day (GD 12-21) exposure results from this study indicate a dose-dependent, age-related morphological change in LC-Mt which are linked to reductions in testosterone biosynthesis genes / proteins expression, specifically StAR and P450scc.
authors.affiliation: Department of Toxicology, Azabu University School of Veterinary Medicine.
authors.forename: Masaya
authors.initials: M
authors.lastname: Motohashi
authors.forename: Michael F
authors.initials: MF
authors.lastname: Wempe
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mutou
authors.forename: Yuya
authors.initials: Y
authors.lastname: Okayama
authors.forename: Norio
authors.initials: N
authors.lastname: Kansaku
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikegami
authors.forename: Masao
authors.initials: M
authors.lastname: Asari
authors.forename: Shin
authors.initials: S
authors.lastname: Wakui
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics* / Q000378:metabolism*; D003993:Dibutyl Phthalate / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics*; D007985:Leydig Cells / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure*; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D051122:Scavenger Receptors, Class B / Q000235:genetics; D013739:Testosterone / Q000096:biosynthesis*; D013997:Time Factors; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D000098682:Steroidogenic Acute Regulatory Protein; D003993:Dibutyl Phthalate; D013739:Testosterone; D002786:Cholesterol Side-Chain Cleavage Enzyme