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. 2015 Apr:52:57-61.
doi: 10.1016/j.reprotox.2015.02.003. Epub 2015 Feb 16.

Very low-dose (femtomolar) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) disrupts steroidogenic enzyme mRNAs and steroid secretion by human luteinizing granulosa cells

M G Baldridge  1 , G T Marks  2 , R G Rawlins  3 , R J Hutz  4
Affiliations

Very low-dose (femtomolar) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) disrupts steroidogenic enzyme mRNAs and steroid secretion by human luteinizing granulosa cells

M G Baldridge et al. Reprod Toxicol. 2015 Apr.

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.

Keywords: Dioxin; Estrogen; Granulosa cells; Low dose; Ovary; RT-qPCR.

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Figures

Figure 1
Figure 1. Estrogen Accumulation by hLGC Treated with 3.1 fM TCDD
Estradiol accumulation by human luteinizing granulosa cells (hLGC) treated in vitro with 3.1 fM TCDD at various time intervals. Values are given as a percentage relative to accumulation by untreated control cells (control = 100%).
Figure 2
Figure 2. Average Relative Fold Change of Aromatase and Side Chain Cleavage Treated with 3.1 fM TCDD
Relative fold changes as determined by RT-qPCR of mRNA expression of side chain cleavage (diamonds) and aromatase (squares) in cells treated with 3.1 fM concentration of TCDD. Fold changes are relative to untreated hGLC normalized to RPL13.
See this image and copyright information in PMC

References

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