Antagonistic Effects of a Mixture of Low-Dose Nonylphenol and Di-N-Butyl Phthalate (Monobutyl Phthalate) on the Sertoli Cells and Serum Reproductive Hormones in Prepubertal Male Rats In Vitro and In Vivo
Antagonistic Effects of a Mixture of Low-Dose Nonylphenol and Di-N-Butyl Phthalate (Monobutyl Phthalate) on the Sertoli Cells and Serum Reproductive Hormones in Prepubertal Male Rats In Vitro and In Vivo
复制标题
小剂量壬基酚和邻苯二甲酸二正丁酯（邻苯二甲酸单丁酯）混合物对青春期前雄性大鼠体外和体内支持细胞和血清生殖激素的拮抗作用
DOI：
10.1371/journal.pone.0093425
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发表时间：
2014-03-27
期刊：
影响因子：
3.7
通讯作者：
Li, Dongmei
中科院分区：
文献类型：
--
作者：
Hu, Yang;Wang, Ruoyu;Li, Dongmei
雌激素化学物质壬基酚（NP）和抗雄激素剂邻苯二甲酸二正丁酯（DBP）被认为是广泛存在的环境内分泌干扰物（EDC），在某些实验动物（例如小鼠和大鼠）中高剂量使用时，会对雄性生殖和发育产生不利影响。鉴于环境中各种类型的 EDC 普遍共存，它们的综合影响值得澄清。在本研究中，我们试图通过数学模型的定量数据分析来确定NP和DBP对雄性大鼠睾丸支持细胞和血清中生殖内分泌激素的混合影响。在体外实验中，使用DBP的活性代谢物邻苯二甲酸单丁酯（MBP）代替DBP。从 9 日龄 Sprague-Dawley 大鼠中分离支持细胞，然后单独或联合使用 NP 和 MBP 进行治疗。测试了细胞活力、细胞凋亡、坏死、膜完整性和抑制素 B 浓度。在体内实验中，大鼠在出生后 23-35 天接受单一或联合 NP 和 DBP 治疗。记录血清生殖激素水平。接下来，采用布利斯独立模型来分析从体外和体内研究获得的定量数据。拮抗作用被确定为 NP 和 DBP (MBP) 的混合效应。在这项研究中，我们证明了 Bliss Independence 模型在预测雌激素和抗雄激素药物之间相互作用的潜力。
The estrogenic chemical nonylphenol (NP) and the antiandrogenic agent di-n-butyl phthalate (DBP) are regarded as widespread environmental endocrine disruptors (EDCs) which at high doses in some species of laboratory animals, such as mice and rats, have adverse effects on male reproduction and development. Given the ubiquitous coexistence of various classes of EDCs in the environment, their combined effects warrant clarification. In this study, we attempted to determine the mixture effects of NP and DBP on the testicular Sertoli cells and reproductive endocrine hormones in serum in male rats based on quantitative data analysis by a mathematical model. In the in vitro experiment, monobutyl phthalate (MBP), the active metabolite of DBP, was used instead of DBP. Sertoli cells were isolated from 9-day-old Sprague-Dawley rats followed by treatment with NP and MBP, singly or combined. Cell viability, apoptosis, necrosis, membrane integrity and inhibin-B concentration were tested. In the in vivo experiment, rats were gavaged on postnatal days 23–35 with a single or combined NP and DBP treatment. Serum reproductive hormone levels were recorded. Next, Bliss Independence model was employed to analyze the quantitative data obtained from the in vitro and in vivo investigation. Antagonism was identified as the mixture effects of NP and DBP (MBP). In this study, we demonstrate the potential of Bliss Independence model for the prediction of interactions between estrogenic and antiandrogenic agents.