Correlation between dioxin and endometriosis: an epigenetic route to unravel the pathogenesis of the disease.
BACKGROUND
Environmental toxicants can act as endocrine disrupters on the female reproductive system. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is resistant to degradation and due to its lipophilic nature, accumulates in the fat tissue and in the food chain. Human and animal exposure to TCDD affects levels of the steroid receptors and steroid-responsive gene expression and has an impact on metabolism and serum transport of steroids. Gene expression is commonly altered in endometriosis and in the eutopic endometrium of women with the disease. Aberrantly expressed genes include those associated with the regulation of transcription, proliferation, sex steroid metabolism, apoptosis, cell cycle, the immune response and cell adhesion.


METHODS
In this paper, we review the evidence about TCDD's effect on eutopic and ectopic endometrium, in order to unravel the machinery behind the dysregulation of immune and hormonal homeostasis caused by this environmental toxicant.


CONCLUSIONS
The evidence collected in this review suggests that TCDD could modulate transcription at multiple levels, including the epigenetic level, and via microRNAs, thus disturbing the physiologic processes mediated through the aryl hydrocarbon receptor pathways. Exposure to TCDD also modulates the immune response by influencing the production and action of endometrial cytokines and chemokines, destroying mucosal immunity of the reproductive tract and re-directing the tissue distribution and behavior of leukocytes. Despite this large body of evidence, current human-based epidemiological studies on the association between TCDD and endometriosis remain controversial.
Department of Environmental Sciences, Safety, Territory, Food and Health, University of Messina, Via C. Valeria 1, 98125, Messina, Italy.
Vincenza
V
Sofo
Department of Gynecology and Obstetrics, Münster University Hospital, 48149, Münster, Germany.
Martin
M
Götte
Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Via C. Valeria 1, 98125, Messina, Italy. antlagana@unime.it.
Antonio Simone
AS
Laganà
Department of Environmental Sciences, Safety, Territory, Food and Health, University of Messina, Via C. Valeria 1, 98125, Messina, Italy.
Francesca Maria
FM
Salmeri
Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Via C. Valeria 1, 98125, Messina, Italy.
Onofrio
O
Triolo
Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Via C. Valeria 1, 98125, Messina, Italy.
Emanuele
E
Sturlese
Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Via C. Valeria 1, 98125, Messina, Italy.
Giovanni
G
Retto
Department of Environmental Sciences, Safety, Territory, Food and Health, University of Messina, Via C. Valeria 1, 98125, Messina, Italy.
Maria
M
Alfa
Department of Pediatric, Gynecological, Microbiological and Biomedical Sciences, University of Messina, Via C. Valeria 1, 98125, Messina, Italy.
Roberta
R
Granese
Department of Obstetrics and Gynecology, São Paulo University (USP), São Paulo, Brazil.
Mauricio Simões
MS
Abrão
D000818:Animals; D004147:Dioxins / Q000378:metabolism*; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism*; D004717:Endometrium / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects / Q000378:metabolism*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins
2,3,7,8-Tetrachlorodibenzo-p-dioxin; Aryl hydrocarbon receptor; Endometriosis; Epigenetics; Sex hormone receptors