Ceratonia siliqua L. pod Effects on Viability Gene Expression of Endometrial Mesenchymal Stromal/Stem Cells Isolated from Women with Endometriosis-Associated Infertility
نویسندگان
1 Stem Cell Technology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
2 Department of Obstetrics and Gynaecology, Shiraz School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
3 Department of Obstetrics and Gynaecology, Shiraz School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
4 Maternal-Foetal Medicine Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
5 Stem Cell Technology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
6 Pharmaceutical Sciences Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
7 Phytopharmaceutical Technology and Traditional Medicine Incubator, Shiraz University of Medical Sciences, Shiraz, Iran
8 Department of Obstetrics and Gynaecology, Shiraz School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
9 The Persian Gulf Marine Biotechnology Research Centre, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
10 The Persian Gulf Marine Biotechnology Research Centre, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
11 Department of Anatomy, School of Biomedical Sciences, Medicine and Health, UNSW Sydney, Sydney, Australia
12 Infertility Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
13 Infertility Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
14 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
15 Stem Cell Technology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
16 Medicinal and Natural Products Chemistry Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
17 Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran
18 Infertility Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
19 General Surgery, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
20 General Surgery, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
21 Department of Oncology, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
doi
10.22074/ijfs.2023.2007228.1496چکیده
Background: This study aims to investigate the effects of carob (Ceratonia siliqua L.) pod extract (CPE) on theviability of human endometrial mesenchymal stromal/stem cells (EnMSCs) and its impact on mRNA and protein expressionsof DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B), histone deacetylase 1 (HDAC1), matrixmetalloproteinase-2 (MMP2), and cyclooxygenase-2 (COX-2) in endometriotic patients.Materials and Methods: In this experimental study, EnMSCs were derived from endometrium of patients with ovarianendometrioma (OMA-EnMSCs group) and deep infiltrative endometriosis (DIE) samples of 10 endometriosisassociatedinfertility (EAI) women (E-EnMSCs group) and compared to EnMSCs derived from the endometrium ofan endometriosis-free, normal woman as the control group (C-EnMSCs). The metabolic activity of the control andcase groups were evaluated by treating them with different concentrations of CPE. Cell viability was analysed byMTT. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to evaluatethe expression of specific genes at the mRNA and protein levels, respectively.Results: Treatment with 0.8 and 2 μg/mL of CPE downregulated COX-2 and HDAC1 in the E-EnMSC groupcompared to the C-EnMSCs group. Treatment with 0.8 μg/mL of CPE also decreased MMP2 and DNMT3B geneexpressions. The COX-2 and DNMT3A genes were significantly upregulated after treatment with 2 μg/mL of CPE.Expressions of the COX-2, HDAC1, DNMT1, DNMT3A, and DNMT3B peptides decreased in the all three groups after treatment with 0.8 and 2 μg/mL of CPE. Gas chromatography-mass spectroscopy (GC-MS) analysis of CPEidentified 14 bioactive compounds. Molecular docking showed the best position of each bioactive compound on thedifferent target proteins that are involved in the process of apoptosis in EnMSCs.Conclusion: In vitro and in silico analyses of CPE bioactive compounds show that they may downregulate the cellinflammatory pathway involved in the pathophysiology of endometriosis.
