Reproductive outcomes in rat female offspring from male rats co-exposed to rosuvastatin and ascorbic acid during pre-puberty

Author(s)

Araujo Leite, Gabriel Adan ^{[1, 2]} ; Figueiredo, Thamiris Moreira ^[1] ; Pacheco, Taina Louise ^[1] ; Guerra, Marina Trevizan ^[1] ; Anselmo-Franci, Janete Aparecida ^[3] ; Kempinas, Wilma De Grava ^[1]

Affiliation

^[1] Sao Paulo State Univ, UNESP, Inst Biosci, Dept Morphol, Botucatu, SP - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Inst Biol, Grad Program Cell & Struct Biol, Campinas - Brazil

^[3] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES; v. 81, n. 17, p. 873-892, 2018.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 14/13659-3 - Short and long-term effects of the exposure to rosuvastatin, in the presence or absence of vitamin C, during prepuberty, on the rat male reproductive systemShort and long-term effects of the exposure to rosuvastatin, in the presence or absence of vitamin C, during prepuberty, on the rat male reproductive system
• Grantee: Thamiris Moreira Figueiredo
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/22495-1 - Male rats exposed to rosuvastatin during prepuberty in the absence or presence of vitamin C: immediate and late effects on genital system and the fertility of generations F0 and F1
• Grantee: Gabriel Adan Araújo Leite
• Support Opportunities: Scholarships in Brazil - Doctorate