2,3,7,8-Tetrachlorodibenzo-p-dioxin increases glycodelin gene and protein expression in human endometrium.
BACKGROUND
Glycodelin (GdA) is an immunosuppressive endometrial glycoprotein critical for embryonic implantation and pregnancy establishment.


OBJECTIVE
The aim of the present study was to examine the effect of dioxin [2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)] on GdA production in human endometrial cells.


METHODS
Controlled endometrial explant (EE) and cell cultures were used in this study.


METHODS
Work was conducted at university hospital research laboratories in Bern, Switzerland, and in San Francisco, California.


METHODS
Ovulatory women provided endometrial biopsies in the proliferative or secretory phase.


METHODS
EEs and cells were cultured without and with TCDD.


METHODS
GdA protein and gene expression were quantified.


RESULTS
A 2.5-fold increase in GdA production was demonstrated in EEs treated with 10 nm TCDD for 9 d. Fluorography revealed a 3- to 4-fold increase in new GdA biosynthesis and secretion in TCDD-treated endometrial epithelial cells. Because the action of dioxin is mediated by the aryl hydrocarbon receptor (AhR), we ascertained that primary epithelial and Ishikawa cells express AhR. Dose responses to TCDD and expressed AhR were established in transiently transfected Ishikawa cells using luciferase fusion vectors containing 1.0 kb of 5' flanking DNA relative to the GdA transcriptional start site but not when shorter promoter constructs were used. A dioxin response element was mapped to nucleotides -539 to -533 of the gene promoter and verified by site-directed mutagenesis.


CONCLUSIONS
We demonstrated a direct AhR-mediated effect of dioxin on GdA gene transcription and protein secretion that might influence human female fertility.
Mueller
Michael D
MD
Endometriosis Center, Department of Obstetrics and Gynaecology, Inselspital, University of Bern, Effingerstrasse 102, 3010 Bern, Switzerland. michel.mueller@insel.ch
Vigne
Jean-Louis
JL
Streich
Matthias
M
Tee
Meng Kian
MK
Raio
Luigi
L
Dreher
Ekkehard
E
Bersinger
Nick A
NA
Taylor
Robert N
RN
D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D000071816:Glycodelin; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011257:Pregnancy Proteins / Q000235:genetics* / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
D004785:Environmental Pollutants; D000071816:Glycodelin; D006023:Glycoproteins; C045246:PAEP protein, human; D000072317:Polychlorinated Dibenzodioxins; D011257:Pregnancy Proteins; D018336:Receptors, Aryl Hydrocarbon