Maternal exposure to ibuprofen can affect the programming of the hypothalamus of the male offspring

Author(s)

Balin, Paola da Silva ^[1] ; Jorge, Barbara Campos ^[1] ; Ribeiro Leite, Andressa Rejani ^[1] ; Borges, Cibele Santos ^[1] ; Oba, Eunice ^[2] ; Ramo Silva, Erick Jose ^[3] ; de Barros, Aline Lima ^[1] ; Castro Horta-Junior, Jose de Anchieta ^[4] ; Arena, Arielle Cristina ^{[1, 5]}

Affiliation

^[1] Univ Estadual Paulista, Inst Biosci Botucatu, Dept Morphol, UNESP, Dist Rubido Jr S-N, Caixa Postal 510, Botucatu, SP - Brazil

^[2] Univ Estadual Paulista, Fac Vet Med, Dept Anim Reprod, UNESP, Botucatu, SP - Brazil

^[3] Univ Estadual Paulista, Inst Biosci Botucatu, Dept Pharmacol, UNESP, Botucatu, SP - Brazil

^[4] Univ Estadual Paulista, Inst Biosci Botucatu, Dept Anat, UNESP, Botucatu, SP - Brazil

^[5] Univ Estadual Paulista, Ctr Toxicol Assistance CEATOX, Inst Biosci Botucatu, UNESP, Botucatu, SP - Brazil

• Document type: Journal article
• Source: REGULATORY TOXICOLOGY AND PHARMACOLOGY; v. 111, MAR 2020.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 16/12110-3 - Male reproductive parameters of rats exposed perinatally to Ibuprofen: morphological, seminal, behavioral and molecular aspects.
• Grantee: Arielle Cristina Arena
• Support Opportunities: Regular Research Grants