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孕期接触倍他米松致雌性大鼠生殖障碍。

Reproductive disorders in female rats after prenatal exposure to betamethasone.

机构信息

Departments of Morphology, Institute of Biosciences, Univ Estadual Paulista-UNESP, Distrito de Rubião Junior s/n°, 18618-970, Botucatu, SP, Brazil.

Departments of Pharmacology, Institute of Biosciences, Univ Estadual Paulista-UNESP, Distrito de Rubião Junior s/n°, 18618-970, Botucatu, SP, Brazil.

出版信息

J Appl Toxicol. 2017 Sep;37(9):1065-1072. doi: 10.1002/jat.3457. Epub 2017 Mar 21.

Abstract

Betamethasone is the drug of choice for antenatal treatment, promoting fetal lung maturation and decreasing mortality. Previous studies in rats reported male programming and alteration in sperm parameters and sexual behavior following intrauterine betamethasone exposure. The impact on the female reproductive development is not known. In this study, rat female offspring was assessed for sexual development, morphophysiology of the reproductive tract and fertility after maternal exposure to 0.1 mg kg of betamethasone or vehicle on gestational days 12, 13, 18 and 19. The treatment promoted reduction of litter weight on postnatal day 1, morphological masculinization in females, delay in the age of puberty onset, reduction in estrus number, increase in estrous cycle length and increase in luteinizing hormone serum levels and uterus weight. The females from the betamethasone group showed an increase of myometrial uterine area and decrease in endometrial uterine area. These animals also performed less lordosis during the sexual behavior test and showed impaired reproductive performance. The uterus showed higher contraction in the treated group as shown by a pharmacological assay. In conclusion, prenatal betamethasone exposure in rats promoted female masculinization, altered sexual development and reproductive parameters. Copyright © 2017 John Wiley & Sons, Ltd.

摘要

倍他米松是产前治疗的首选药物,可促进胎儿肺成熟并降低死亡率。先前在大鼠中的研究报告称,子宫内给予倍他米松会导致雄性编程和精子参数以及性行为改变。但其对女性生殖发育的影响尚不清楚。在这项研究中,对大鼠雌性后代进行了评估,以评估其在母鼠于妊娠第 12、13、18 和 19 天接受 0.1mg/kg 倍他米松或载体处理后,在性发育、生殖道形态生理学和生育能力方面的变化。该处理可导致产后第 1 天的窝重减少,雌性出现形态学男性化,青春期起始年龄延迟,发情次数减少,发情周期延长,血清促黄体生成素水平升高和子宫重量增加。倍他米松组的雌性动物表现出子宫肌层面积增加和子宫内膜子宫面积减少。这些动物在性行为测试中表现出的背弓姿势减少,并表现出生殖性能受损。通过药理学检测,发现子宫在处理组中的收缩增加。总之,大鼠产前暴露于倍他米松会导致雌性雄性化、性发育和生殖参数改变。版权所有 © 2017 约翰威立父子公司

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