Lower sperm quality and testicular and epididymal structural impairment in adult rats exposed to rosuvastatin during prepuberty

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 10mg kg(-1) day(-1), administered orally by gavage, from postnatal day 21 until preputial separation (average of 45days for controls and 49days 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. Prepubertal exposure to rosuvastatin promoted reduced serum follicle-stimulating hormone, luteinizing hormone and testosterone concentrations and increased serum prolactin and estradiol concentrations, leading to a hormonal deregulation on sexual maturity. Furthermore, rosuvastatin-exposed groups exhibited augmented germ cell death, decreased expression of androgen receptors on testis and epididymis and lower expression of aquaporin-9 on epididymal epithelium. In conclusion, administration of rosuvastatin to juvenile male rats impaired male reproduction at adulthood.