Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois.
Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign, Urbana, Illinois.
Toxicol Sci. 2019 May 1;169(1):246-259. doi: 10.1093/toxsci/kfz047.
Phthalates are synthetic chemicals with widespread human exposure due to their use as additives in consumer products. Phthalate diesters are hydrolyzed in the environment and in the body to monoesters that may be more toxic than the parent compounds. This study tested the hypothesis that adult mouse antral follicles, but not neonatal ovaries, are able to metabolize an environmentally relevant mixture of phthalates. Whole neonatal ovaries and isolated adult antral follicles from CD-1 mice were cultured in media treated with vehicle control or 0.1-10 µg/ml of a mixture composed of 35% diethyl phthalate (DEP), 21% di(2-ethylhexyl) phthalate (DEHP), 15% dibutyl phthalate (DBP), 15% diisononyl phthalate (DiNP), 8% diisobutyl phthalate (DiBP), and 5% benzylbutyl phthalate (BzBP). After 4 days of culture, media were subjected to high-performance liquid chromatography tandem mass spectrometry to measure the amounts of diester phthalates and monoester metabolites. Ovaries and follicles were collected to measure the gene and protein expression of the enzymes required for phthalate metabolism. Monoester metabolites for all phthalates except DiNP were detected in the media for both culture types at most doses. The long-chain phthalates (BzBP, DEHP, and DiNP) were metabolized less than the short-chain phthalates (DEP, DBP, and DiBP) compared with respective controls. Expression of metabolizing enzymes was observed for all treatment groups in both culture types. These data indicate that mouse ovaries are capable of metabolizing low doses of phthalates and suggest that metabolic capacity differs for follicles at different stages of development.
邻苯二甲酸酯是一种合成化学物质，由于其作为消费品添加剂的广泛使用，人类接触广泛。邻苯二甲酸酯二酯在环境中和体内被水解为单酯，其毒性可能比母体化合物更大。本研究检验了这样一个假设，即成年小鼠窦卵泡，但不是新生卵巢，能够代谢环境相关的邻苯二甲酸酯混合物。将来自 CD-1 小鼠的整个新生卵巢和分离的成年窦卵泡在含有对照溶剂或 0.1-10μg/ml 由 35%邻苯二甲酸二乙酯 (DEP)、21%邻苯二甲酸二(2-乙基己基)酯 (DEHP)、15%邻苯二甲酸二丁酯 (DBP)、15%邻苯二甲酸二异壬酯 (DiNP)、8%邻苯二甲酸二异丁酯 (DiBP) 和 5%邻苯二甲酸丁基苄基酯 (BzBP) 组成的混合物处理的培养基中进行培养。培养 4 天后，用高效液相色谱串联质谱法测量二酯邻苯二甲酸酯和单酯代谢物的含量。收集卵巢和卵泡以测量用于邻苯二甲酸代谢的酶的基因和蛋白质表达。在大多数剂量下，两种培养类型的培养基中都检测到除 DiNP 外所有邻苯二甲酸的单酯代谢物。与各自的对照相比，长链邻苯二甲酸酯（BzBP、DEHP 和 DiNP）的代谢量低于短链邻苯二甲酸酯（DEP、DBP 和 DiBP）。两种培养类型的所有处理组均观察到代谢酶的表达。这些数据表明，小鼠卵巢能够代谢低剂量的邻苯二甲酸，并表明不同发育阶段的卵泡代谢能力不同。
