Department of Morphology, São Paulo State University (UNESP), Institute of Biosciences, Botucatu, Brazil.
Department of Morphology, Stomatology and Physiology, School of Dentistry, USP - University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
J Appl Toxicol. 2018 Jun;38(6):914-929. doi: 10.1002/jat.3599. Epub 2018 Feb 19.
The increase of obesity, bad eating habits and the lack of physical exercises are highly related to dyslipidemias. Rosuvastatin is a lipid-lowering drug and has been indicated to prevent cardiovascular diseases and to treat dyslipidemias due to its higher efficiency to reduce serum cholesterol concentrations. This study aimed to evaluate the reproductive adverse effects on sexual maturity due to rosuvastatin exposure in juvenile male rats during prepuberty. Three groups were randomly formed with newly weaned rats: control, whose rats received saline solution 0.9% and rosuvastatin at doses of 3 or 10 mg kg day , administered orally by gavage, from postnatal day 21 until preputial separation (average of 45 days for controls and 49 days for statin-treated animals), indicative of puberty onset. Male rats were maintained until sexual maturity and were killed on postnatal day 110. In the rosuvastatin-treated groups, the results showed diminished follicle-stimulating hormone, luteinizing hormone and testosterone concentrations, increased estradiol and prolactin concentrations, histopathologic alterations on testis and epididymis and decreased sperm quality. Moreover, statin-exposed groups showed decreased expression of androgen receptor on testis and epididymis and lower expression of aquaporin-9 on epididymal epithelium. In conclusion, administration of rosuvastatin to prepubertal male rats provoked long-term hormonal deregulation and impaired reproduction at adulthood.
肥胖、不良饮食习惯和缺乏体育锻炼与血脂异常高度相关。 瑞舒伐他汀是一种降脂药物，由于其降低血清胆固醇浓度的效率更高，已被证明可预防心血管疾病和治疗血脂异常。本研究旨在评估瑞舒伐他汀暴露于青春期前雄性幼鼠对性成熟的生殖不良影响。将刚断奶的大鼠随机分为三组：对照组，大鼠接受 0.9%生理盐水；瑞舒伐他汀组，剂量为 3 或 10mg/kg/天，通过灌胃给药，从出生后第 21 天至包皮分离（对照组平均为 45 天，他汀类治疗组为 49 天），提示青春期开始。雄性大鼠维持至性成熟，于出生后第 110 天处死。在瑞舒伐他汀治疗组中，结果显示卵泡刺激素、黄体生成素和睾酮浓度降低，雌二醇和催乳素浓度升高，睾丸和附睾组织学改变，精子质量下降。此外，暴露于他汀类药物的大鼠睾丸和附睾的雄激素受体表达减少，附睾上皮的水通道蛋白-9 表达降低。总之，给青春期前雄性大鼠灌胃瑞舒伐他汀会引起长期的激素失调，并在成年期损害生殖功能。
