Journal
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
Volume 81, Issue 17, Pages 873-892Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15287394.2018.1504702
Keywords
Vitamin C; rosuvastatin; female offspring; reproduction; toxicology
Funding
- Sao Paulo Research Foundation (FAPESP) [013/22495-1, 014/13659-3]
- National Council for Scientific and Technological Development (CNPq) [308842/2013-8]
- Coordination for the Improvement of Higher Education Personnel (CAPES)
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [14/13659-3] Funding Source: FAPESP
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Dyslipidemias are occurring earlier in different countries due to the increase of obesity, bad eating habits, and sedentary lifestyle. Rosuvastatin reduces serum cholesterol; however, several studies associated statin exposure with male reproduction impairment. Ascorbic acid (AA) is an antioxidant substance that plays a protective role in the male reproductive system. Male rats were randomly divided into 6 experimental groups (n=10), which received saline solution 0.9%, 3 or 10mg/kg/day of rosuvastatin, 150mg/day of AA or 3 or 10mg/kg/day of rosuvastatin associated with 150mg/day of AA from post-natal day (PND) 23 until PND 53. On PND 100, males were mated with non-treated female rats to obtain the female pups. The day of vaginal opening and the first estrus were assessed in the offspring. Two sets of females were euthanized on the first estrus after PND 42 and PND 75 to evaluate the histology of reproductive organs and hormone levels. A third set was used for sexual behavior and fertility test around PND 75. Female offspring from males exposed or co-exposed to the higher dose of statinexhibited a lower number of corpora lutea during puberty. On sexual maturity, the experimental group from males that were exposed to 3mg displayed lower uterine luminal epithelium area. Paternal exposure to rosuvastatin at pre-puberty diminished uterine luminal epithelium in female offspring suggesting epigenetic changes were initiated by statin. Ascorbic acid co-administered to pre-pubertal males was able to ameliorate the reproductive damage in rat female offspring in adulthood.
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