Expression of Ah Receptor and Dioxin-Related Genes in Human Uterine Endometrium in Women with or without Endometriosis.

Abstract

Abstract.2,3,7,8-Tetrachlorodibenzo p-dioxin (TCDD) has been suggested as a possible etiologic factor for endometriosis, a condition in which endometrium-like tissues are present outside the uterus. The prevailing view pertaining to the origin of endometriotic cells is that they are from eutopic endometrial cells which regurgitate through fallopian tubes. In order to get insight into the possible involvement of TCDD in the pathogenesis of endometriosis, we suspected that TCDD may act differently on the endometrium with or without endometriosis. To address this, we examined the presence of messenger RNAs of arylhydrocarbon receptor (AhR), AhR nuclear translocator (Arnt) and two dioxin-responsive genes, cytochrome P-450 1B1 (CYP1B1) and downstream of tyrosine kinases (p62(dok)), in the endometrium of women with or without endometriosis using semi-quantitative reverse transcription-polymerase chain reaction. All the genes were expressed throughout the menstrual cycle. The expression level of p62(dok) was higher in the proliferative phase than in the secretory phase. In contrast, the expression levels of AhR, Arnt and CYP 1 B 1 seemed to be constant during the cycle. In terms of the comparison between non-endometriosis and endometriosis group, the mRNA levels of AhR, Arnt, CYP 1 B 1 and p62(dok) were essentially similar. Interestingly, AhR mRNA level was significantly lower in smokers than in non-smokers.Based on the regression analysis, significant linear and positive correlations were observed between AhR and Arnt mRNA levels, and between Arnt and p62(dok) mRNA levels. In summary, expression of AhR and dioxin-related genes in the endometrium did not differ in women with or without endometriosis.

Expression of the arylhydrocarbon receptor in the peri-implantation period of the mouse uterus and the impact of dioxin on mouse implantation

“…Although the expression of the AhR mRNA and protein was identified in utero-placental tissue in several species (Dolwick et al, 1993;Igarashi et al, 1999;Küchenhoff et al, 1999;Tscheudschilsuren et al, 1999aTscheudschilsuren et al, , 1999bBuchanan et al, 2000;Pitt et al, 2001;Kitajima et al, 2004), this is the first report on the spatio-temporal expression of the AhR protein in the pregnant mouse uterus with implanted embryos during the peri-implantation period. In the present study, intense AhR expression was detected in the mouse uterine vasculature throughout this dynamic reproductive process.…”

ERβ- and Prostaglandin E2-Regulated Pathways Integrate Cell Proliferation via Ras-like and Estrogen-Regulated Growth Inhibitor in Endometriosis

“…Analysis of the additional 69 ER␤ targets will further establish the role of ER␤ in endometriosis. Interesting candidates among the remaining ER␤ targets include the serum-and glucocorticoid-regulated kinase (SGK1), which regulates endometrial cell survival in response to oxidative stress, thioredoxin (TXNRD1), which encodes an enzyme involved in the regulation of intracellular reactive oxygen species, or cytochrome P450 1B1 (CYP1B1), an estradiol-metabolizing enzyme that is associated with endometriosis and increased exposure to dioxins (33,36,42,43). Future studies using ER␤-ChIP-Seq in E-Osis are warranted to obtain a comprehensive data set of ER␤ transcriptional targets in E-Osis.…”

Dioxin may promote inflammation-related development of endometriosis

“…All TCDD-like ligands act via the AhR, a ligand-activated orphan nuclear receptor that is expressed in both somatic endometrial cells (74,75) and in immune cells (76)(77)(78)(79). In each of these cell types, the unliganded AhR is present in the cytosol as a multiprotein complex bound to chaperone proteins.…”