Zhou Changqing, Flaws Jodi A
Department of Comparative Biosciences, University of Illinois, Urbana, Illinois 61802.
Toxicol Sci. 2017 Mar 1;156(1):217-229. doi: 10.1093/toxsci/kfw245.
Phthalates are used in building materials, medical devices, and personal care products. Most studies on phthalates have focused on single phthalates, but it is important to study mixtures of phthalates because humans are exposed to such mixtures daily. We tested the hypothesis that phthalate mixture exposure decreases antral follicle growth, compromises steroidogenic capacity, and induces atresia. Antral follicles from adult CD-1 mice were cultured with vehicle control or phthalate mixture (1-500 µg/ml) for 96 h. The mixture was made of 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. During culture, antral follicle diameters were measured every 24 h to monitor growth. After culture, media were subjected to measurements of sex steroid hormones and follicles were subjected to evaluation of gene expression and atresia. The phthalate mixture (100 and 500 µg/ml) decreased antral follicle growth starting at 24 h compared to controls. The mixture at 10, 100, and 500 µg/ml also decreased androstenedione, testosterone, estrone, and estradiol levels compared to control. The mixture (10, 100, and 500 µg/ml) reduced atresia rating, but it induced more oocyte fragmentation compared to control. The phthalate mixture at different doses adversely affected cell cycle regulators, antioxidant enzymes, apoptotic factors, steroidogenic enzymes, and receptors. Collectively, these data indicate that exposure to an environmentally relevant phthalate mixture reduces antral follicle growth, induces oocyte fragmentation, and decreases hormone production by adversely affecting the expression of cell cycle regulators, apoptotic factors, steroidogenic enzymes, and receptors.
邻苯二甲酸盐被用于建筑材料、医疗设备和个人护理产品中。大多数关于邻苯二甲酸盐的研究都集中在单一邻苯二甲酸盐上，但研究邻苯二甲酸盐混合物很重要，因为人类每天都会接触到此类混合物。我们检验了以下假设：接触邻苯二甲酸盐混合物会减少窦卵泡生长、损害类固醇生成能力并诱导闭锁。将成年CD-1小鼠的窦卵泡与溶剂对照或邻苯二甲酸盐混合物（1-500μg/ml）培养96小时。该混合物由35%的邻苯二甲酸二乙酯、21%的邻苯二甲酸二（2-乙基己基）酯、15%的邻苯二甲酸二丁酯、15%的邻苯二甲酸二异壬酯、8%的邻苯二甲酸二异丁酯和5%的苄基丁基邻苯二甲酸酯组成。在培养过程中，每24小时测量一次窦卵泡直径以监测生长情况。培养后，对培养基进行性甾体激素测量，对卵泡进行基因表达和闭锁评估。与对照组相比，邻苯二甲酸盐混合物（100和500μg/ml）从24小时开始就减少了窦卵泡生长。与对照组相比，10、100和500μg/ml的混合物也降低了雄烯二酮、睾酮、雌酮和雌二醇水平。该混合物（10、100和500μg/ml）降低了闭锁评分，但与对照组相比，它诱导了更多的卵母细胞碎片化。不同剂量的邻苯二甲酸盐混合物对细胞周期调节因子、抗氧化酶、凋亡因子、类固醇生成酶和受体产生了不利影响。总体而言，这些数据表明，接触与环境相关的邻苯二甲酸盐混合物会通过对细胞周期调节因子、凋亡因子、类固醇生成酶和受体的表达产生不利影响，从而减少窦卵泡生长、诱导卵母细胞碎片化并降低激素产生。
