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

Autor: Balin PDS; Department of Morphology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista, Botucatu (UNESP), São Paulo State, Brazil., Jorge BC; Department of Morphology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista, Botucatu (UNESP), São Paulo State, Brazil., Leite ARR; Department of Morphology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista, Botucatu (UNESP), São Paulo State, Brazil., Borges CS; Department of Morphology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista, Botucatu (UNESP), São Paulo State, Brazil., Oba E; Department of Animal Reproduction, Faculty of Veterinary Medicine, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo State, Brazil., Silva EJR; Department of Pharmacology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo State, Brazil., de Barros AL; Department of Morphology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista, Botucatu (UNESP), São Paulo State, Brazil., Horta-Júnior JAC; Department of Anatomy, Institute of Biosciences of Botucatu, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo State, Brazil., Arena AC; Department of Morphology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista, Botucatu (UNESP), São Paulo State, Brazil; Center of Toxicological Assistance (CEATOX), Institute of Biosciences of Botucatu, Univ. Estadual Paulista, Botucatu (UNESP), São Paulo State, Brazil. Electronic address: arielle.arena@unesp.br.
Jazyk: angličtina
Zdroj: Regulatory toxicology and pharmacology : RTP [Regul Toxicol Pharmacol] 2020 Mar; Vol. 111, pp. 104576. Date of Electronic Publication: 2020 Jan 03.
DOI: 10.1016/j.yrtph.2020.104576
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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