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Amodiaquine‐induced reproductive toxicity in adult male rats
Author(s) -
Niu YanRu,
Wei Bing,
Chen Bi,
Xu LiHua,
Jing Xia,
Peng CaiLing,
Ma TianZhong
Publication year - 2016
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.22603
Subject(s) - spermatogenesis , biology , reproductive toxicity , testosterone (patch) , endocrinology , medicine , sertoli cell , andrology , tunel assay , toxicity , apoptosis , luteinizing hormone , immunostaining , reproductive system , hormone , immunohistochemistry , immunology , biochemistry
SUMMARY Amodiaquine (AQ) is routinely prescribed as an anti‐malarial drug. Here, we evaluated AQ‐induced toxicity in the male reproductive system. Eighty adult male Sprague‐Dawley rats were randomly divided into four groups that received distilled water (control) or daily doses of 5 mg/kg body weight, 10 mg/kg, or 15 mg/kg AQ for 2 weeks. Testes morphology was analyzed using hematoxylin‐and‐eosin staining, terminal dUTP nicked‐end labeling (TUNEL), and immunostaining whereas protein expression was determined by Western blotting. AQ dose‐dependently led to abnormal spermatogenesis. Disruption of the blood‐testis barrier and increased germ cell apoptosis were observed in all three AQ‐treated groups. Interestingly, AQ‐induced damage of spermatogenesis recovered over time, based on the survival of promyelocytic leukemia zinc‐finger (PLZF)‐positive, undifferentiated spermatogonia. Serum levels of luteinizing hormone and testosterone, as well as testicular testosterone levels, were not significantly altered in AQ‐treated groups compared with controls. Collectively, our study suggests that AQ exerts substantial acute side effects on the reproductive systems of adult male rats by inducing the apoptosis of differentiating spermatogenic cells and disruption of blood‐testis barrier function. Mol. Reprod. Dev. 83: 174–182, 2016. © 2015 Wiley Periodicals, Inc .