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倍他米松宫内暴露对未成年大鼠睾丸和附睾的影响。

Impact of intrauterine exposure to betamethasone on the testes and epididymides of prepubertal rats.

机构信息

Department of Morphology, São Paulo State University (UNESP), Institute of Biosciences, Botucatu, SP, Brazil.

Department of Morphology, São Paulo State University (UNESP), Institute of Biosciences, Botucatu, SP, Brazil.

出版信息

Chem Biol Interact. 2018 Aug 1;291:202-211. doi: 10.1016/j.cbi.2018.06.030. Epub 2018 Jun 25.

Abstract

Therapy with betamethasone, a synthetic glucocorticoid, is used in cases of preterm birth risk, in order to promote fetal lung maturation, and decrease neonatal mortality and morbidity. However, late reproductive disorders related to the prenatal exposure to this compound have been reported by our Laboratory, in both male and female rats. Thus, the present study aimed to evaluate the impact of betamethasone on postnatal reproductive development, during pre-puberty, of male offspring exposed in utero to this synthetic glucocorticoid. For this purpose, pregnant Wistar rats were allocated into two groups: Control, treated with saline, and the group treated with betamethasone at 0.1 mg/kg/day. Control and betamethasone groups were treated with intramuscular injection on gestational days 12, 13, 18 and 19, critical days of prenatal reproductive development. The treatment is associated with reduced body and organ weights, disorders in initial reproductive parameters of pre-pubertal male offspring exposed in utero to betamethasone, such as reduction of anogenital distance, alterations in histomorphometric parameters and immunostaining pattern of androgen and estrogen receptors on testicles and epididymides. Our results suggest that prenatal exposure to betamethasone potentially causes reproductive reprogramming and impairs male postnatal reproductive development. This data raise concerns about the use of betamethasone for human antenatal therapy.

摘要

倍他米松是一种合成的糖皮质激素,用于有早产风险的病例,以促进胎儿肺成熟,降低新生儿死亡率和发病率。然而,我们实验室已经报道了产前暴露于这种化合物与雄性和雌性大鼠的生殖后期障碍有关。因此,本研究旨在评估倍他米松对宫内暴露于这种合成糖皮质激素的雄性后代的青春期前生殖发育的影响。为此,将怀孕的 Wistar 大鼠分为两组:对照组,用生理盐水处理;倍他米松组,用 0.1mg/kg/天的倍他米松处理。对照组和倍他米松组在妊娠第 12、13、18 和 19 天(产前生殖发育的关键期)接受肌肉注射治疗。该治疗与体重和器官重量减轻有关,还与宫内暴露于倍他米松的青春期前雄性后代的初始生殖参数异常有关,例如,肛殖距离缩短,睾丸和附睾中雄激素和雌激素受体的组织形态计量学参数和免疫染色模式改变。我们的结果表明,产前暴露于倍他米松可能导致生殖重编程,并损害雄性后代的产后生殖发育。这些数据引起了对人类产前治疗中使用倍他米松的关注。

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