Male Sprague-Dawley Rats Exposed to In Utero Di(n-butyl) Phthalate

Author:

Shirai Masaru1,Wakui Shin12,Wempe Michael F.3,Mutou Tomoko4,Oyama Noriko4,Motohashi Masaya1,Takahashi Hiroyuki2,Kansaku Norio1,Asari Masao1,Hano Hiroshi2,Endou Hitoshi5

Affiliation:

1. Department of Toxicology and Veterinary Anatomy, Azabu University School of Veterinary Medicine, Kanagawa, Japan

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

3. School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, Colorado

4. Drug Safety Testing Center, Saitama, Japan

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

Abstract

When 100 mg/kg/day of di( n-butyl) phthalate (DBP) was intragastrically administered to pregnant Sprague-Dawley rats throughout gestation days 12 to 21, the male pups had similar body weights with no apparent physical differences (e.g., litter size, sex ratio) compared to that of the vehicle group. However, prominent age-related morphological alterations in the smooth endoplasmic reticulum (sER) of testicular Leydig cells (LCs) were observed once these animals reached puberty. At weeks 5 to 7, the abundant sER with non-dilated cisternae was distributed in LCs. Subsequently, although the number of LCs significantly increased, the amount of sER was significantly decreased at 9 to 14 weeks of age and had disappeared at 17 weeks. In contrast, the number of LCs and the amount of sER in LCs of the lower dose groups (10, 30, and 50 mg/kg/day) were similar to those of the vehicle group. Further, serum testosterone levels in the 100 mg/kg dose group were significantly lower during 5 to 17 weeks of age. While their luteinizing hormone (LH) level was significantly lower at 5 to 7 weeks of age, it became significantly higher during 9 to 17 weeks. The amount of sER in LCs decreased with age with the increase in LCs proliferation and serum LH levels in rat exposed in utero to DBP in a dose-dependent manner.

Publisher

SAGE Publications

Subject

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

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