Hu Yang, Wang Ruoyu, Xiang Zou, Qian Weiping, Han Xiaodong, Li Dongmei
Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China.
Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, China.
PLoS One. 2014 Mar 27;9(3):e93425. doi: 10.1371/journal.pone.0093425. eCollection 2014.
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.
雌激素类化学物质壬基酚（NP）和抗雄激素剂邻苯二甲酸二正丁酯（DBP）被视为广泛存在的环境内分泌干扰物（EDCs），在某些实验动物物种（如小鼠和大鼠）中，高剂量时会对雄性生殖和发育产生不利影响。鉴于环境中各类EDCs普遍共存，它们的联合效应有待阐明。在本研究中，我们试图基于数学模型的定量数据分析，确定NP和DBP对雄性大鼠睾丸支持细胞及血清中生殖内分泌激素的混合效应。在体外实验中，使用DBP的活性代谢物单丁基邻苯二甲酸酯（MBP）代替DBP。从9日龄的斯普拉格-道利大鼠中分离出支持细胞，然后单独或联合用NP和MBP处理。检测细胞活力、凋亡、坏死、膜完整性和抑制素B浓度。在体内实验中，在出生后第23至35天对大鼠进行单次或联合NP和DBP处理。记录血清生殖激素水平。接下来，采用布利斯独立模型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。在本研究中，我们证明了布利斯独立模型在预测雌激素类和抗雄激素剂之间相互作用方面的潜力。
