Atypical Leydig Cell Hyperplasia in Adult Rats with Low T and High LH Induced by Prenatal Di(n-butyl) Phthalate Exposure

Author:

Wakui Shin12,Takahashi Hiroyuki2,Mutou Tomoko3,Shirai Masaru1,Jutabha Promsuk4,Anzai Naohiko4,Wempe Michael F.5,Kansaku Norio1,Hano Hiroshi2,Inomata Tomo1,Endou Hitoshi6

Affiliation:

1. Department of Toxicology and Laboratory Animal Science, Azabu University School of Veterinary Medicine, Kanagawa, Japan

2. Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan

3. Drug Safety Testing Center, Saitama, Japan

4. Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan

5. School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

6. J-Pharma Co., Ltd., Tokyo, Japan

Abstract

The present study describes atypical Leydig cell (LC) hyperplasia in 20-week-old Sprague-Dawley rats with low testosterone and high luteinizing hormone levels after prenatal administration of 100 mg/kg/day di( n-butyl) phthalate on days 12 to 21 postconception. Light microscopy revealed LC hyperplasia surrounded by severely degenerated seminiferous tubules. Aggregated LCs had large ovoid nuclei with nucleoli and abundant eosinophilic cytoplasm. Immunohistochemical analysis showed expression of proliferating cell nuclear antigen and vimentin in many hyperplastic LCs. Electron microscopy revealed atypical nuclei, abundant free ribosomes, stripped rough endoplasmic reticulum, intermediate-size filaments, elongated cytoplasmic filopodia, atypical tight junctions, and cilia formations, but smooth endoplasmic reticulum was scarcely observed.

Publisher

SAGE Publications

Subject

Cell Biology,Toxicology,Molecular Biology,Pathology and Forensic Medicine

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