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Male reproductive toxicity and b-luteinizing hormone gene expression in sexually mature and immature rats exposed to 2-bromopropane

Institut für Klinische Pharmakologie und Toxikologie, Freie Universität Berlin, Garystraûe 5, 14195 Berlin, Germany; National Evaluation Center for the Toxicology of Fertility Regulating Drugs, Shanghai 200032, China

A S Faqi

Institut für Klinische Pharmakologie und Toxikologie, Freie Universität Berlin, Garystraûe 5, 14195 Berlin, Germany; Department of Anatomy, Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA

J Yang

X Ding

X Jiang

National Evaluation Center for the Toxicology of Fertility Regulating Drugs, Shanghai 200032, China

I Chahoud

Institut für Klinische Pharmakologie und Toxikologie, Freie Universität Berlin, Garystraûe 5, 14195 Berlin, Germany

1. 1 The reproductive effects of 2-bromopropane (2-BP) in sexually mature and immature male Sprague-Dawley rats were investigated. The animals were randomly divided into three treatment groups and one control group each of which comprised six mature and six immature rats. The treated groups were injected s.c. 200, 600 and 1800 mg/kg of 2-BP on 5 days a week for 5-7 weeks and the control group received the vehicle.
   
2. 2 The absolute and relative testis weights were significantly reduced in 600 and 1800 mg/kg b.w. dose groups in both mature and immature rats. The absolute epididymis, prostate, seminal vesicle, and pituitary weights and the relative epididymis weights, however, were significant only at the highest dose level used in both mature and immature rats.
   
3. 3 The sperm concentration and sperm viability in epididymal duct decreased and the percentage of abnormal sperm increased in a dose-dependent manner in both mature and immature rats. Additionally, serum testosterone level was significantly decreased in all dose groups in mature rats, and was significantly reduced only in the group treated with the middle and highest dose in immature rats.
   
4. 4 In both mature and immature rats treated with 200 and 600 mg/kg, the seminiferous tubules were atrophied and all types of germ cells were decreased in number. At the highest dose level, the effect was more marked showing severely atrophied seminiferous tubules and a complete loss of all types of germ cells.
   
5. 5 The mating, pregnancy and fertility indices were significantly reduced in the 600 and 1800 mg/kg groups. Additionally, at the highest dose group the number of implantations and viable fetuses per litter were reduced and the resorption rate was increased significantly.
   
6. 6 In the mature rats, the b-LH gene expression increased significantly in the 1800 mg/kg group when compared to the control group.
   
7. 7 It can be concluded that 2-BP induces alterations in both neuro-endocrine axis and the reproductive tract under the present experimental conditions. The no observed adverse effect level (NOAEL) in this study could be estimated to be lower than 200 mg/kg/b.w. based on the alteration in testicular morphology as well as on sperm parameters observed at the dose level of 200 mg/kg.
   

Key Words: 2-bromopropane • male reproductive organ • sperm parameter • testosterone • male fertility • b-luteinizing hormone gene

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