title: Very low-dose (femtomolar) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) disrupts steroidogenic enzyme mRNAs and steroid secretion by human luteinizing granulosa cells.
abstract: 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.
authors.affiliation: College of Natural Sciences and Health Sciences, Department of Health and Medicine, Carroll University, Waukesha, WI 53186, United States. Electronic address: mbaldrid@carrollu.edu.
authors.forename: M G
authors.initials: MG
authors.lastname: Baldridge
authors.affiliation: College of Natural Sciences and Health Sciences, Department of Physical Sciences, Carroll University, Waukesha, WI 53186, United States.
authors.forename: G T
authors.initials: GT
authors.lastname: Marks
authors.affiliation: Rush Copley Center for Reproductive Health, Aurora, IL 60504, United States.
authors.forename: R G
authors.initials: RG
authors.lastname: Rawlins
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 5321, United States; Department of OB/GYN, Medical College of Wisconsin, United States.
authors.forename: R J
authors.initials: RJ
authors.lastname: Hutz
mesh_terms: D001141:Aromatase / Q000235:genetics; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants; D004958:Estradiol / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D034461:Luteinization; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D012333:RNA, Messenger / Q000032:analysis; D013723:Teratogens
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D013723:Teratogens; D004958:Estradiol; D001141:Aromatase; C561410:CYP19A1 protein, human; D002786:Cholesterol Side-Chain Cleavage Enzyme
keywords: Dioxin; Estrogen; Granulosa cells; Low dose; Ovary; RT-qPCR