Expression of AKR1B1, AKR1C3 and other genes of prostaglandin F2α biosynthesis and action in ovarian endometriosis tissue and in model cell lines
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This study investigated the expression of AKR1B1, AKR1C3, and other prostaglandin F2α biosynthesis and action genes in ovarian endometriosis tissue and model cell lines.
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Abstract
Endometriosis is a frequent benign gynecological disease characterized by endometrial tissue outside the uterine cavity. The estimated prevalence in the general population is 6-10%, but this reaches 30-50% in women with infertility and/or pain. As ectopic tissue within the pelvic cavity provokes inflammation, endometriosis is also considered a chronic inflammatory disease, and is characterized by increased peritoneal fluid levels of prostaglandin (PG)E2 and PGF2α. The AKR1B1 and AKR1C3 enzymes act as PG synthases and catalyze reduction of PGH2 to PGF2α, and PGD2 to 9α,11β-PGF2α, respectively. AKR1B1 and AKR1C3 may thus be associated with increased PGF2α production in endometriosis patients, as supported by our previous report of increased AKR1C1-AKR1C3 mRNA levels in endometriotic tissue, compared to control endometrium. Here, we initially evaluated PGF2α concentrations in peritoneal fluid from endometriosis patients and healthy women. We also examined expression of AKR1B1, AKR1C3 and other genes involved in PGF2α biosynthesis, metabolism, and action in ovarian endometriosis tissue versus healthy endometrium, and in peritoneal endometriosis and control endometrium model cell lines. Compared to controls, increased PGF2α concentrations in peritoneal fluid of patients were supported by endometriotic tissue showing increased AKR1B1 mRNA and protein levels, but unchanged AKR1C3 protein levels. Among genes involved in PGF2α biosynthesis, metabolism and action PLA2G2A, PTGS2/COX-2, ABCC4 and PTGFR were up-regulated, mRNA levels of SLCO2A, PTGDS and HPGDS were unchanged, and genes PLA2G4A and HPGD were down-regulated in diseased tissue. All of these PGF2α-associated genes were also expressed in control endometrial HIEEC epithelial and HIESC stromal cell lines, and in peritoneal endometriosis 12-Z epithelial and 22-B stromal cell lines. Higher expression of PLA2G2A, PTGS2, AKR1B1, AKR1C3 and ABCC4 was seen in 22-B endometriosis cells compared to HIESC control cells. These cell models characterized in this study will enable further investigations into the role of PGF2α in the pathophysiology of endometriosis and the involvement of AKR1B1 and AKR1C3.
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- Integrated analysis of genome-wide gene expression and DNA methylation profiles reveals candidate genes in ovary endometriosis 2023
- Is intracrinology of endometriosis relevant in clinical practice? A systematic review on estrogen metabolism 2022
- The Genetic-Epigenetic Pathophysiology of Endometriosis: A Surgeon’s View 2020
- Establishment of endometriotic models: the past and future 2020
- Effect of Tahiti lime (Citrus latifolia) juice on the Production of the PGF2α/PGE2 and Pro-Inflammatory Cytokines involved in Menstruation 2020
- Future directions in endometriosis treatment: discovery and development of novel inhibitors of estrogen biosynthesis 2019
- Aldo-keto reductase 1C3—Assessment as a new target for the treatment of endometriosis 2019
- Analysis of key candidate genes and pathways of endometriosis pathophysiology by a genomics-bioinformatics approach 2019
- Is it time for a paradigm shift in drug research and development in endometriosis/adenomyosis? 2018
- PTGFR activation promotes the expression of PTGS-2 and growth factors via activation of the PKC signaling pathway in bovine endometrial epithelial cells 2018
- SULFATION PATHWAYS: Contribution of intracrine oestrogens to the aetiology of endometriosis 2018
- Pathogenesis of endometriosis: the genetic/epigenetic theory 2018
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