Baldridge M G, Marks G T, Rawlins R G, Hutz R J
College of Natural Sciences and Health Sciences, Department of Health and Medicine, Carroll University, Waukesha, WI 53186, United States.
College of Natural Sciences and Health Sciences, Department of Physical Sciences, Carroll University, Waukesha, WI 53186, United States.
Reprod Toxicol. 2015 Apr;52:57-61. doi: 10.1016/j.reprotox.2015.02.003. Epub 2015 Feb 16.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic congener of the polyhalogenated aromatic hydrocarbons (PAH), which causes anatomical abnormalities and developmental defects, impairs ovulation and reduces fertility. TCDD's endocrine-disrupting effects are, in part, caused by a direct action at the ovary. Herein we investigated the in-vitro effects of environmentally relevant doses of TCDD on estradiol-17β (E2) production by human luteinizing granulosa cells (hLGC) obtained from women stimulated for in-vitro fertilization (IVF). TCDD at all concentrations tested (3.1fM, 3.1pM and 3.1nM) significantly decreased E2 secretion when assayed for by radioimmunoassay (RIA). Herein we confirm that TCDD alters E2 secretion by hLGC in a time-, not dose-dependent fashion and are the first to show decreases in E2 secretion with fM concentrations of TCDD. Using real-time quantitative PCR (RT-qPCR), the decreased E2 secretion correlates with a decrease in the mRNA expression levels two enzymes in the estrogen biosynthesis pathway: CYP11A1 and CYP19A1.
2,3,7,8-四氯二苯并-对-二恶英（TCDD）是多卤代芳烃（PAH）中毒性最强的同系物，它会导致解剖结构异常和发育缺陷，损害排卵并降低生育能力。TCDD的内分泌干扰作用部分是由其对卵巢的直接作用引起的。在此，我们研究了环境相关剂量的TCDD对从接受体外受精（IVF）刺激的女性中获取的人黄体化颗粒细胞（hLGC）分泌雌二醇-17β（E2）的体外影响。通过放射免疫测定法（RIA）检测发现，所有测试浓度（3.1fM、3.1pM和3.1nM）的TCDD均显著降低了E2的分泌。在此我们证实，TCDD以时间而非剂量依赖的方式改变hLGC分泌E2的情况，并且我们首次发现fM浓度的TCDD会导致E2分泌减少。使用实时定量PCR（RT-qPCR）方法发现，E2分泌减少与雌激素生物合成途径中两种酶CYP11A1和CYP19A1的mRNA表达水平降低相关。
