Adult exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of the hypothalamic-pituitary-testicular axis

被引:207
作者
Wisniewski, Patricia [1 ]
Romano, Renata M. [1 ]
Kizys, Marina M. L. [2 ]
Oliveira, Kelen C. [2 ]
Kasamatsu, Teresa [2 ]
Giannocco, Gisele [2 ]
Chiamolera, Maria I. [2 ]
Dias-da-Silva, Magnus R. [2 ]
Romano, Marco A. [1 ]
机构
[1] State Univ Ctr Ooeste, Dept Pharm, Lab Reprod Toxicol, BR-85040080 Guarapuava, Parana, Brazil
[2] Univ Fed Sao Paulo Unifesp EPM, Lab Mol & Translat Endocrinol, Dept Med, Escola Paulista Med, Sao Paulo, SP, Brazil
关键词
Bisphenol A; Sperm function; Sperm production; Gonadotropins; Gene expression; Testosterone; ESTROGEN-RECEPTOR; OXIDATIVE STRESS; GENE-EXPRESSION; SEMEN QUALITY; 5TH EDITION; SPERMATOGENESIS; EXTRACTION; MORPHOLOGY; DIAGNOSIS; CHEMICALS;
D O I
10.1016/j.tox.2015.01.002
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Reproductive physiology involves complex biological processes that can be disrupted by exposure to environmental contaminants. The effects of bisphenol A (BPA) on spermatogenesis and sperm quality is still unclear. The objective of this study was to investigate the reproductive toxicity of BPA at dosages considered to be safe (5 or 25 mg BPA/kg/day). We assessed multiple sperm parameters, the relative expression of genes involved in the central regulation of the hypothalamic-pituitary-testicular axis, and the serum concentrations of testosterone, estradiol, LH and FSH. BPA exposure reduced sperm production, reserves and transit time. Significant damage to the acrosomes and the plasma membrane with reduced mitochondrial activity and increased levels of defective spermatozoa may have compromised sperm function and caused faster movement through the epididymis. BPA exposure reduced the serum concentrations of testosterone, LH and FSH and increased the concentration of estradiol. The relative gene expression revealed an increase in gonadotropin releasing hormone receptor (Gnrhr), luteinizing hormone beta (Lhb), follicle stimulating hormone beta (Fshb), estrogen receptor beta (Esr2) and androgen receptor (Ar) transcripts in the pituitary and a reduction in estrogen receptor alpha (Esr1) transcripts in the hypothalamus. In this study, we demonstrated for the first time that adult male exposure to BPA caused a reduction in sperm production and specific functional parameters. The corresponding pattern of gene expression is indicative of an attempt by the pituitary to reestablish normal levels of LH, FSH and testosterone serum concentrations. In conclusion, these data suggest that at dosages previously considered nontoxic to reproductive function, BPA compromises the spermatozoa and disrupts the hypothalamic-pituitary-gonadal axis, causing a state of hypogonadotropic hypogonadism. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
引用
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页码:1 / 9
页数:9
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