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母体暴露于邻苯二甲酸二正丁酯(DBP)后雄性大鼠子代前列腺形态发生的改变。

Alterations in prostate morphogenesis in male rat offspring after maternal exposure to Di-n-butyl-phthalate (DBP).

作者信息

de Mello Santos Talita, da Silveira Lívia Teresa Ribeiro, Rinaldi Jaqueline Carvalho, Scarano Wellerson Rodrigo, Domeniconi Raquel Fantin

机构信息

Department of Anatomy, Institute of Biosciences, Univi Estadual Paulista/UNESP, Botucatu, SP, Brazil.

Department of Morphology, Institute of Biosciences, Univi Estadual Paulista/UNESP, Botucatu, SP, Brazil.

出版信息

Reprod Toxicol. 2017 Apr;69:254-264. doi: 10.1016/j.reprotox.2017.03.010. Epub 2017 Mar 21.

Abstract

Prostate morphogenesis is regulated by androgens hormones and modulated by morphogenetic proteins such as Bone Morphogenetic Proteins (BMPs). This study aims to investigate the effects on prostate development in male offspring and differentiation after gestational and lactational maternal exposure to Di-n-butyl-phthalate (DBP), an important environmental contamination. Pregnant Wistar rats received 100 or 500mg/kg of DBP (DBP100 and DBP500), by gavage, from gestation day 15 (GD15) until postnatal day 21 (PND21). The pups were euthanized on PND1 and PND21. Anogenital distance and testosterone levels decreased in animals from exposed mothers (DBP100 and 500) on PND1. A three-dimensional reconstruction model of the prostatic urethra showed reduction in the prostatic buds in the DBP500 group. AR expression and α-actin immunoreactivity decreased, and BMP-4 expression was lower on PND1 for DBP500. These results showed that DBP exposure, especially at a higher dose, delayed prostate morphogenesis by reducing the testosterone/AR axis and BMP-4 expression.

摘要

前列腺形态发生受雄激素调节,并受形态发生蛋白如骨形态发生蛋白(BMPs)的调控。本研究旨在调查孕期和哺乳期母体暴露于重要环境污染物邻苯二甲酸二丁酯(DBP)后,对雄性后代前列腺发育和分化的影响。怀孕的Wistar大鼠从妊娠第15天(GD15)至出生后第21天(PND21),通过灌胃给予100或500mg/kg的DBP(DBP100和DBP500)。幼崽在出生后第1天(PND1)和第21天(PND21)实施安乐死。出生后第1天,暴露组母亲的子代(DBP100和DBP500)的肛门生殖器距离和睾酮水平降低。前列腺尿道的三维重建模型显示,DBP500组的前列腺芽减少。出生后第1天,DBP500组的AR表达和α-肌动蛋白免疫反应性降低,且BMP-4表达较低。这些结果表明,暴露于DBP,尤其是高剂量时,会通过降低睾酮/AR轴和BMP-4表达来延迟前列腺形态发生。

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