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Maternal exposure to ibuprofen can affect the programming of the hypothalamus of the male offspring.
Regulatory Toxicology and Pharmacology ( IF 3.0 ) Pub Date : 2020-01-03 , DOI: 10.1016/j.yrtph.2020.104576 Paola da Silva Balin 1 , Bárbara Campos Jorge 1 , Andressa Rejani Ribeiro Leite 1 , Cibele Santos Borges 1 , Eunice Oba 2 , Erick José Ramo Silva 3 , Aline Lima de Barros 1 , José de Anchieta Castro Horta-Júnior 4 , Arielle Cristina Arena 5
Regulatory Toxicology and Pharmacology ( IF 3.0 ) Pub Date : 2020-01-03 , DOI: 10.1016/j.yrtph.2020.104576 Paola da Silva Balin 1 , Bárbara Campos Jorge 1 , Andressa Rejani Ribeiro Leite 1 , Cibele Santos Borges 1 , Eunice Oba 2 , Erick José Ramo Silva 3 , Aline Lima de Barros 1 , José de Anchieta Castro Horta-Júnior 4 , Arielle Cristina Arena 5
Affiliation
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Ibuprofen, a non-steroidal anti-inflammatory drug, inhibits the activity of cyclooxygenase enzyme, leading to reduction in Prostaglandin E2 (PGE2) production. Due to the importance of PGE2 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.
中文翻译：
孕妇暴露于布洛芬会影响雄性后代下丘脑的程序设计。
布洛芬是一种非甾体类抗炎药，可抑制环氧合酶的活性，从而降低前列腺素E2（PGE2）的产生。由于PGE2在促进雄性胎儿脑部男性化方面的重要性，因此本研究旨在评估子宫内和哺乳期布洛芬及其后期反应对雄性大鼠生殖参数的影响。从妊娠后第15天到出生后第21天，每天从管饲法对怀孕的大鼠每天每口饲喂布洛芬（10、30或60 mg / kg）或媒介物（对照组），并在性发育过程中和成年成年后评估晚期生殖作用生活在雄性后代。暴露于布洛芬的男性体重和肛门生殖器距离减少，睾丸后裔和包皮分离的年龄延迟。成年后，精巢细胞的核体积，睾丸激素水平和正常精子形态百分比降低。暴露于布洛芬的所有动物均表现出雄性交配行为，但是，在另一只雄性存在下，它们也呈现出典型的雌性行为。母体在大脑发育的敏感窗口期间母体接触布洛芬会对雄性大鼠的生殖参数产生不利影响，表明下丘脑的男性化不完全。
更新日期：2020-01-04
中文翻译：
孕妇暴露于布洛芬会影响雄性后代下丘脑的程序设计。
布洛芬是一种非甾体类抗炎药，可抑制环氧合酶的活性，从而降低前列腺素E2（PGE2）的产生。由于PGE2在促进雄性胎儿脑部男性化方面的重要性，因此本研究旨在评估子宫内和哺乳期布洛芬及其后期反应对雄性大鼠生殖参数的影响。从妊娠后第15天到出生后第21天，每天从管饲法对怀孕的大鼠每天每口饲喂布洛芬（10、30或60 mg / kg）或媒介物（对照组），并在性发育过程中和成年成年后评估晚期生殖作用生活在雄性后代。暴露于布洛芬的男性体重和肛门生殖器距离减少，睾丸后裔和包皮分离的年龄延迟。成年后，精巢细胞的核体积，睾丸激素水平和正常精子形态百分比降低。暴露于布洛芬的所有动物均表现出雄性交配行为，但是，在另一只雄性存在下，它们也呈现出典型的雌性行为。母体在大脑发育的敏感窗口期间母体接触布洛芬会对雄性大鼠的生殖参数产生不利影响，表明下丘脑的男性化不完全。
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