Very low-dose (femtomolar) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) disrupts steroidogenic enzyme mRNAs and steroid secretion by human luteinizing granulosa cells |
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| Affiliation: | 1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China;2. Department of Clinical Pharmacy, The First People''s Hospital of Changzhou, Changzhou, China;3. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China;1. Institute of Epigenetics and Epigenomics, Yangzhou University, 48 Wenhui East Road, Yangzhou, Jiangsu 225009, China;2. College of Animal Science and Technology, Yangzhou University, 48 Wenhui East Road, Yangzhou, Jiangsu 225009, China;3. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC 29425, USA;4. Ralph H Johnson Veteran''s Affairs Medical Center, 109 Bee St, 29403, Charleston, SC, USA;5. Union Hospital of Cecil County, 106 Bow St, Elkton, MD 21921, USA |
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| 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 (3.1 fM, 3.1 pM and 3.1 nM) 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. |
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| Keywords: | Dioxin Estrogen Granulosa cells Low dose Ovary RT-qPCR |
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