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

Abstract

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.

Effect of atorvastatin on spermatogenesis in rats: A stereological study

“…Experimental rat studies have reported that statins increase DNA fragmentation in sperm and abnormal sperm rates, while reducing spermatozoa motility [4,5]. Similarly, studies of human males have observed that statins significantly compromise semen quality, particularly sperm motility [6,7].…”

Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty

“…The rosuvastatin doses chosen for this study are based on the lowest and highest doses applied in human therapy for children ( Leite et al, 2018a , Leite et al, 2019b , Leite et al, 2018c ), adapted for rodents considering their body surface area, as proposed for Reagan-Shaw et al ( Reagan‐Shaw et al, 2008 ).…”

“…Previous studies investigating peri -pubertal rosuvastatin exposure in a rodent experimental model revealed that this drug leads to reproductive impairments in male rats. Rosuvastatin can delay pubertal development, reduce sperm quality, impair spermatogenesis, and alter hormonal signaling ( Leite et al, 2014 , Leite et al, 2018a , Leite et al, 2019b ). Also, rosuvastatin exposure in male rats might affect reproductive function in an intergenerational manner, by damaging ovarian and uterine histophysiology of female offspring ( Leite et al, 2018 ).…”

Effect of statin on semen quality characteristics

“…Instead, the negative effects of statins on semen quality characteristics may be due to an alteration in gonadal hormones, mainly testosterone hormone, which is the main controller of spermatogenesis (Banihani, 2018b, 2020; Rogers et al, 2017), and luteinising hormone, which stimulates production of testosterone (Banihani, 2018a; El‐Migdadi, Banihani, & Banihani, 2005). It has been shown that male rats orally administered rosuvastatin at 3 or 10 mg kg −1 day −1 , from postnatal day 21 until preputial, had diminished levels of testosterone, luteinising hormone and follicle‐stimulating hormone (Leite et al, 2014; Leite, Sanabria, et al, 2018). In addition, a study on adult male rats showed that rosuvastatin supplementation at 3 or 10 mg kg −1 day −1 may lead to androgen depletion and germ cell death (Leite et al, 2017).…”