Delayed reproductive development in pubertal male rats exposed to the hypolipemiant agent rosuvastatin since prepuberty

Leite, Gabriel Adan Araújo; Rosa, Josiane de Lima; Sanabria, Marciana; Cavariani, Marília Martins; Franci, Janete Aparecida Anselmo; Pinheiro, Patrícia Fernanda Felipe; Kempinas, Wilma De Grava

doi:10.1016/j.reprotox.2014.01.004

Cited by 35 publications

(44 citation statements)

References 38 publications

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“…In the rosuvastatin-exposed groups, the epididymis showed several histopathologic changes, such as clear cell hyperplasia in the proximal epididymis cauda, which may be associated with delayed epididymal development, as previously reported (Leite et al, 2014), and a higher frequency of leukocyte infiltrate, which may be related to androgen depletion and consequently an increase in inflammatory mediators, such as tumor necrosis factor-α (Chen et al, 2016), leading to an augmentation on the inflammatory response.…”

Section: Discussionsupporting

confidence: 69%

“…Moreover, there was a deregulation in spermatogenesis kinetics with an increased percentage of seminiferous tubules during stages I-VI and a diminution of the frequency of stages VII-VIII in the rosuvastatin-exposed rats. Tanaka et al, 2000) or have associated androgen depletion with germ cell death in the testis (Leite et al, 2014;2017). This study showed increased rate of acidophilic germ cells, indicative of germ cell death, in the seminiferous epithelium of adult animals exposed to the statin.…”

Section: Discussionmentioning

confidence: 66%

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

Leite

Sanabria

Cavariani

et al. 2018

J of Applied Toxicology

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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.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 66%

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

Leite

Sanabria

Cavariani

et al. 2018

J of Applied Toxicology

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“…There were also testicular alterations, such as seminiferous tubules with acidophilic spermatogonia and spermatocytes, especially in stages IX-XIV, that might be related to delayed puberty and decrease of serum testosterone. 66 …”

Section: Prepubertal Androgen Deprivationmentioning

confidence: 99%

Interpreting histopathology in the epididymis

Kempinas

Klinefelter

2014

Spermatogenesis

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“…Moreover, it shows superior inhibitory effects on cholesterol biosynthesis in comparison with other statins (Holdgate et al, 2003;McTaggart, 2003;Olsson et al, 2002). Contrary to the benefits, previous studies showed that statins may interfere with male reproductive development (Leite et al, 2014;, are able to diminish serum testosterone levels (Hsieh & Huang, 2016;Leite et al, 2014;Leite, Figueiredo, Pacheco, et al, 2017; and decrease sperm quality in adult men treated with the medication (Pons-Rejraji et al, 2014).…”

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confidence: 99%

Ascorbic acid supplementation ameliorates testicular hormonal signaling, sperm production and oxidative stress in male rats exposed to rosuvastatin during pre‐puberty

Leite

Barros

Martins

et al. 2018

J of Applied Toxicology

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Dyslipidemias are occurring earlier in the population due to the augmentation of obesity. Rosuvastatin reduces cholesterol and triglycerides; however, previous studies have shown that it may affect male reproduction. Ascorbic acid (AA), an antioxidant compound, plays a protective role in the male reproductive system. This study aimed to evaluate whether pre‐pubertal exposure to rosuvastatin may impair testicular structure and antioxidant status in male rats and if supplementation with AA may alleviate these damages. Male rats were randomly divided into six experimental groups (n = 10) on postnatal day (PND) 23 and received the different treatments by gavage from PND 23 to 53. The experimental groups received vehicle (saline solution 0.9%), 3 or 10 mg/kg/day of rosuvastatin diluted in saline solution 0.9%, supplementation with 150 mg/day of AA, 3 mg/kg/day of rosuvastatin in association with 150 mg/day of AA or 10 mg/kg/day of rosuvastatin associated with 150 mg/day of AA. Testicular parameters were assessed on PND 53 and 110. There were diminished androgen receptors staining in the Sertoli cells and increased germ cell death in rosuvastatin‐exposed groups, in both periods. Spermatids showed lower estrogen alpha‐receptors staining in the group exposed to 10 mg of statin at adulthood. There were androgen depletion and increased lipid peroxidation and catalase activity in statin‐exposed groups. Rosuvastatin exposure during pre‐puberty impaired testicular structure, steroid receptor distribution and increased oxidative stress; however, AA was able to ameliorate the impairment provoked by statin exposure.

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Delayed reproductive development in pubertal male rats exposed to the hypolipemiant agent rosuvastatin since prepuberty

Cited by 35 publications

References 38 publications

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

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

Interpreting histopathology in the epididymis

Ascorbic acid supplementation ameliorates testicular hormonal signaling, sperm production and oxidative stress in male rats exposed to rosuvastatin during pre‐puberty

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