EFFECTS OF FLUTAMIDE ON SEX MATURATION AND BEHAVIOR OF OFFSPRING BORN TO FEMALE RATS TREATED DURING LATE PREGNANCY
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概要
- 論文の詳細を見る
Flutamide, when administered subcutaneously to female rats at doses of 3, 10, or 30 mg/kg/day during late pregnancy (gestational days 16-21), significantly and dose-dependently decreased anogenital distance (AGD) of the male offspring in each dose group compared to controls Significant delays in preputial separation were found in males at a dose of 30 mg/kg, but body weight gain was not inhibited Cryptorchidism and absence of the prostate gland and seminal vesicles were found in males at doses ≥ 10 mg/kg, and testicular hypoplasia at a dose of 30 mg/kg Hypospadias was noted in all dose groups and vaginal pouches at doses of ≥ 10 mg/kg The effects on the accessory reproductive organs were severe, although the effects on the testes themselves were mild However, those effects appeared to become more pronounced with growth, as evaluated on Days 30 and 42 and Weeks 16 to 18 Most of these affected animals displayed cryptorchidism Male offspring exposed to flutamide in utero showed impairments of sexual behavior as adults in a dose-related manner Number and frequency of mounts with intromissions was markedly decreased in all treated groups as compared to controls At 10 mg/kg, no mounting with ejaculation was observed, and at a dose of 30 mg/kg, no mounting with intromission or ejaculation was observed These changes in sexual behavior were closely associated with abnormalities of the external genitalia Animals with hypospadias did not display mounts with ejaculation However, Fl males that copulated at a dose of 3 mg/kg had a normal reproductive function Histological examination of the reproductive organs revealed degeneration of the seminiferous tubules, hypospermatogenesis, and hypoplasia and inflammation of the seminal vesicles and prostate Serum levels of FSH, LH, and testosterone in these animals were comparable between control and all dose groups Therefore, the male reproductive dysfunction seen in the present study could not be attributed to abnormal sex hormone levels during maturation, but to possible demasculinization of the brain and progressively delayed dysmorphorogy of the male genitalia caused by fetal exposure to flutamide
- 日本トキシコロジー学会の論文
- 2004-12-27
著者
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鈴木 浩悦
日本獣医生命科学大学獣医学部
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KOIZUMI Keiji
Toxicological Research Department, Odawara Research Center, Nippon Soda Co., Ltd.
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FUJII Yoshinobu
Toxicological Research Department, Odawara Research Center, Nippon Soda Co., Ltd.
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SAIKA Osamu
Toxicological Research Department, Odawara Research Center, Nippon Soda Co., Ltd.
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SUZUKI Hiroetsu
Nippon Veterinary and Animal Science University
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SAITO Kenichi
Nippon Veterinary and Animal Science University
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SUZUKI Katsushi
Nippon Veterinary and Animal Science University
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SUZUKI Katsushi
Laboratory of Veterinary Physiology, Nippon Veterinary and Life Science University
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Saito Kenichi
Department Of Veterinary Physiology Nippon Veterinary And Life Science University
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Fujii Yoshinobu
Toxicological Research Department Odawara Research Center Nippon Soda Co. Ltd.
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Fujii Yoshinobu
Department Of Electronics And Information Systems Osaka University
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GOTO Kazunori
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka
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Goto K
Toxicological Research Department Odawara Research Center Nippon Soda Co. Ltd.
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Goto Kazunori
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences University Of Shizuoka
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Saika O
Toxicological Research Department Odawara Research Center Nippon Soda Co. Ltd.
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Koizumi Keiji
Toxicological Research Department Odawara Research Center Nippon Soda Co. Ltd.
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Suzuki Katsushi
Laboratory Of Veterinary Physiology Nippon Veterinary And Life Science University
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Suzuki Hiroetsu
Department Of Veterinary Physiology Nippon Veterinary And Animal Science University
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Furuyama Yuko
Imamichi Institute For Animal Reproduction
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KOIZUMI Keiji
Department of Toxicology Research, Odawara Research Center Nippon Soda Co, Ltd
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TAKAORI Hitoshi
Department of Toxicology Research, Odawara Research Center Nippon Soda Co, Ltd
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FURUYAMA Yuko
Department of Toxicology Research, Odawara Research Center Nippon Soda Co, Ltd
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SAIKA Osamu
Department of Toxicology Research, Odawara Research Center Nippon Soda Co, Ltd
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Suzuki Hodaka
Department Of Veterinary Pathology The University Of Tokyo
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Takaori Hitoshi
Department Of Toxicology Research Odawara Research Center Nippon Soda Co Ltd
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