期刊
REGULATORY TOXICOLOGY AND PHARMACOLOGY
卷 111, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yrtph.2020.104576
关键词
Prostaglandins; Brain sexual differentiation; Preoptic area; Sexually dimorphic nucleus; Sexual behavior
资金
- FAPESP -The State of Sao Paulo Research Foundation [2016/12110-3, 2017/039977]
Ibuprofen, a non-steroidal anti-inflammatory drug, inhibits the activity of cyclooxygenase enzyme, leading to reduction in Prostaglandin E-2 (PGE(2)) production. Due to the importance of PGE(2) in promoting the brain masculinization in male fetus, this study aimed to evaluate the effects of in utero and lactational exposure to ibuprofen and their late repercussions on reproductive parameters in male rats. Pregnant rats were exposed to ibuprofen (10, 30 or 60 mg/kg) or vehicle (control group) per gavage daily from gestational day 15 to day 21 after birth, and late reproductive effects were assessed during the sexual development and in the reproductive adult life in the male offspring. Males exposed to ibuprofen had a decrease in body weight and anogenital distance, as well as a delay in the ages of testicular descent and preputial separation. In adulthood, there was a decrease in the Leydig cells nuclei volume, testosterone levels and percentage of normal sperm morphology. All animals exposed to ibuprofen presented male copulatory behavior, however, in the presence of another male, they also presented a female-typical behavior. Maternal exposure to ibuprofen during the sensitive windows of brain development adversely impacted the reproductive parameters of male rats, suggesting an incomplete masculinization of the hypothalamus.
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