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Influence of in utero and lactacional exposure to the anti-inflammatory ibuprofen: late repercussion on male reproductive parameters in rats

Grant number: 17/03997-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2017
Effective date (End): July 31, 2019
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Arielle Cristina Arena
Grantee:Andressa Rejani Ribeiro Leite
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated scholarship(s):17/23356-6 - Impact of inhibiting cerebellar prostaglandin or estradiol production during the second postnatal week on later microglia activation state, BE.EP.IC

Abstract

Prostaglandin E2 (PGE2) is important in the process of hypothalamic sexual differentiation, promoting masculinization of the hypothalamus of males. Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (the third class of medications most commonly used by pregnant women) act through the non-selective inhibition of the enzyme cyclooxygenase (COX-1 and COX-2), leading to a reduction in PGE2. Due to the importance of PGE2 in the process of hypothalamic sexual differentiation, the use of anti-inflammatory drugs during pregnancy is of concern. The objective of this study was to evaluate the possible effects of in utero and lactational exposure to ibuprofen and its late repercussions on reproductive parameters in male rats. For this, pregnant rats will be exposed to three doses of ibuprofen (10; 30; 60 mg / kg) between the last week of pregnancy (gestational days 15-21) and the end of lactation (postnatal days 20) by gavage. After birth, male offspring will be evaluated through the following parameters: body weight determination, anogenital distance and ages of preputial separation and testicular descent. In adult life, these same animals will be investigated for: reproductive organ weights, sperm count, morphology and sperm motility, hormonal dosage, histopathological analysis of the testis, epididymis, Sertoli and Leydig cell counts. The present study, besides providing an opportunity to train qualified human resources, could generate important information for the implementation of governmental public health policies aimed at a greater control of the use of this medication class during pregnancy. (AU)