Results
| PMID | 25446850 |
| Gene Name | PLA2G4A |
| Condition | Endometriosis |
| Association |
Associated |
| Population size | 57 |
| Population details | 57 (29 patients with ovarian endometriosis, 28 control healthy women) |
| Age | Patients: 33 ± 6 yrs, Controls: 41 ± 3 yrs |
| Sex | Female |
| Infertility type | Female infertility |
| Associated genes | PGF2A, AKR1B1, AKR1C3, PLA2G2A, PTGS2/COX-2, ABCC4 and PTGFR , PLA2G4A and HPGD |
| Other associated phenotypes |
Endometriosis |
|
Chem Biol Interact. 2015 Jun 5;234:320-31. doi: 10.1016/j.cbi.2014.11.009. Epub Sinreih, Masa| Anko, Maja| Kene, Neli Hevir| Kocbek, Vida| Rizner, Tea Lanisnik Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.| Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.| Institute of Biochemistry, Faculty of Medicine, University of 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 PGF2alpha. The AKR1B1 and AKR1C3 enzymes act as PG synthases and catalyze reduction of PGH2 to PGF2alpha, and PGD2 to 9alpha,11beta-PGF2alpha, respectively. AKR1B1 and AKR1C3 may thus be associated with increased PGF2alpha 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 PGF2alpha concentrations in peritoneal fluid from endometriosis patients and healthy women. We also examined expression of AKR1B1, AKR1C3 and other genes involved in PGF2alpha 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 PGF2alpha 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 PGF2alpha 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 PGF2alpha-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 PGF2alpha in the pathophysiology of endometriosis and the involvement of AKR1B1 and AKR1C3. Mesh Terms: 3-Hydroxysteroid Dehydrogenases/*genetics/metabolism| Adult| Aldehyde Reductase/*genetics/metabolism| Case-Control Studies| Cell Line| Dinoprost/*biosynthesis/*genetics| Down-Regulation/genetics| Endometriosis/*genetics/metabolism| Endometrium/met |
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