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青春期前暴露于布洛芬会损害成年雄性大鼠的精子参数,并损害下一代。

Pre-pubertal exposure to ibuprofen impairs sperm parameters in male adult rats and compromises the next generation.

机构信息

Department of Structural and Functional Biology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista - Botucatu (UNESP) , São Paulo, Brazil.

College of Health Science, Federal University of Grande Dourados - Dourados , Mato grosso do Sul, Brazil.

出版信息

J Toxicol Environ Health A. 2020 Aug 17;83(15-16):559-572. doi: 10.1080/15287394.2020.1786483. Epub 2020 Jul 2.

DOI:10.1080/15287394.2020.1786483
PMID:32615883
Abstract

Ibuprofen is one of the most commonly prescribed anti-inflammatory drugs in pediatric practice. This drug inhibits the cyclooxygenase enzyme, reducing the production of prostaglandin, an important mediator on male reproductive function. We examined if pre-pubertal treatment with ibuprofen in male rats can affect the reproductive parameters of these animals in adult life and on their descendants. Male rats (23 days old) received ibuprofen (0; 2.4; 7.2 or 14.3 mg/kg/day), per gavage, from postnatal day (PND) 23 to 53. At sexual maturity, treated males were placed with untreated females for obtaining the next generation (F1). The highest dose of ibuprofen interfered in sexual behavior and reduced the fertility potential of these animals in adulthood. Additionally, the ibuprofen treatment altered the sperm quantity and quality, as evidenced by a decrease in sperm motility and in the daily sperm production in the testis. Testosterone levels were also reduced by pre-pubertal treatment. The paternal treatment with this drug also influenced the reproductive outcomes of progeny. The male offspring from males treated exhibited acceleration in sperm transit time in the epididymis and the number and volume of Leydig cell nuclei were decreased, while the estrous cyclicity was displayed and the fertility potential reduced in the female offspring. The pre-pubertal ibuprofen-treatment caused negative reproductive impacts in adulthood, compromising sperm quality and quantity, as well as interfered in the reproductive outcomes of the next generation.

摘要

布洛芬是儿科实践中最常用的抗炎药之一。这种药物抑制环氧化酶,减少前列腺素的产生,前列腺素是男性生殖功能的重要介质。我们研究了在雄性幼鼠的青春期前给予布洛芬是否会影响这些动物在成年后的生殖参数及其后代。雄性幼鼠(23 天大)从出生后第 23 天到第 53 天每天通过灌胃接受布洛芬(0;2.4;7.2 或 14.3 mg/kg/天)。在性成熟时,用未处理的雌性与处理过的雄性交配以获得下一代(F1)。最高剂量的布洛芬会干扰性行为,并降低这些动物在成年期的生育能力。此外,布洛芬处理还改变了精子的数量和质量,表现为精子活力降低和睾丸内每日精子生成减少。睾酮水平也因青春期前的处理而降低。这种药物的亲代处理也会影响后代的生殖结果。来自接受处理的雄性的雄性后代表现出附睾中精子转运时间加速,以及莱迪希细胞核的数量和体积减少,而雌性后代则表现出发情周期和生育能力降低。青春期前的布洛芬处理导致成年后生殖受到负面影响,影响精子质量和数量,并干扰下一代的生殖结果。

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