Publications by authors named "Sepideh Khodaverdi"

23 Publications

  • Page 1 of 1

Association Between Vitamin D Receptor (VDR) and Vitamin D Binding Protein (VDBP) Genes Polymorphisms to Endometriosis Susceptibility in Iranian Women.

Reprod Sci 2021 May 4. Epub 2021 May 4.

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Endometriosis is a chronic inflammatory disease that has been reported to be associated with immune system dysfunction. On the other hand, the effect of Vitamin D as an immune modulator and its relation with several autoimmune and inflammatory diseases has been previously investigated. Moreover, several studies have reported the polymorphisms of VDR and VDBP genes can change the functions of these molecules. Therefore, these polymorphisms may be influential on endometriosis pathogenesis. In this study, we aimed at evaluating the association between VDR gene (FokI (F/f), BsmI (B/b), ApaI (A/a), TaqI (T/t)), and VDBP gene (GC*1S, GC*1F, and GC*2) polymorphisms with endometriosis in Iranian women population. This case-control study was performed on 120 women with endometriosis and 110 healthy women. ARMS-PCR and PCR-RFLP methods were used to inspect polymorphisms in VDR and VDBP genes, respectively. Based on the results, there was no statistically significant difference between the cases with endometriosis and control subjects in terms of genotypes and allele frequencies of VDR and VDBP gene polymorphisms. These data suggest that VDR and VDBP gene polymorphisms may have no role in endometriosis susceptibility in Iranian women.
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http://dx.doi.org/10.1007/s43032-021-00598-zDOI Listing
May 2021

The effects of resveratrol on the expression of VEGF, TGF-β, and MMP-9 in endometrial stromal cells of women with endometriosis.

Sci Rep 2021 Mar 15;11(1):6054. Epub 2021 Mar 15.

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Resveratrol is a phytochemical with anti-angiogenic, anti-inflammatory, and antioxidant properties. The present study has evaluated the effect of resveratrol on the expression of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β) and matrix metalloproteinase-9 (MMP-9) as factors related to endometriosis progression. Thirteen eutopic (EuESCs) and 8 ectopic (EESCs) endometrial stromal cells from women with endometriosis and 11 control endometrial stromal cells (CESCs) were treated with resveratrol (100 µM) for 6, 24 and 48 h. The gene and protein expression levels of VEGF, TGF-β, and MMP-9 were measured using real-time PCR and ELISA methods, respectively. Results showed that the basal gene and protein expression of VEGF and MMP-9 were higher in EESCs compared to EuESCs and CESCs (P < 0.01 to  < 0.001 and P < 0.05 to  < 0.01 respectively). Also, resveratrol treatment decreased the gene and protein expression of VEGF and MMP-9 in EuESCs, EESCs and CESCs (P < 0.05 to  < 0.01 and P < 0.05 to  < 0.01 respectively) and gene and protein expression of TGF-β in EESCs and EuESCs (P < 0.05 to  < 0.01). The effect of resveratrol in reduction of VEGF gene expression was statistically more noticeable in EESCs compared to EuESCs and CESCs (P < 0.05). According to the findings, resveratrol may ameliorate endometriosis progression through reducing the expression of VEGF, TGF-β, and MMP-9 in endometrial stromal cells (ESCs).
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http://dx.doi.org/10.1038/s41598-021-85512-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961000PMC
March 2021

The effect of agar substrate on growth and development of cryopreserved-thawed human ovarian cortical follicles in organ culture.

Eur J Obstet Gynecol Reprod Biol 2021 Mar 29;258:139-145. Epub 2020 Dec 29.

Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. Electronic address:

Objective: To preserve human ovarian tissue structure and improve follicular growth and survival during in-situ culture, various biomaterials are used. In this study we aimed to compare agar as a cultivation substrate with matrigel-coated insert in order to achieve an optimum system for in-situ human follicle culture.

Study Design: Frozen-thawed human ovarian cortical tissues were cultured on either matrigel-coated inserts or agar-soaked substrates. The proportion of morphologically viable and degenerated follicles at different developmental stages, secreted hormonal levels, and apoptotic and proliferation gene expressions were compared between the cultured groups after 7-days of culture.

Results: The follicular growth was not significantly different between the two cultured groups, although showing higher percentage of growing follicles in agar cultured group. The secreted hormonal levels didn't have any difference between two cultured groups. Although the apoptotic gene expressions didn't show any difference between the cultured groups, the apoptotic index was lower in agar cultured group. In addition, Ki67 gene expression, a proliferative marker, showed a significantly higher expression in agar cultured group.

Conclusion: Based on the results, agar is as suitable as matrigel-coated inserts for the survival and growth of follicles during culture. Therefore, agar can be an inexpensive alternative substrate for culturing frozen-thawed human ovarian cortical strips.
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http://dx.doi.org/10.1016/j.ejogrb.2020.12.048DOI Listing
March 2021

Vitamin D deficiency as a risk factor for endometriosis in Iranian women.

J Reprod Immunol 2021 02 17;143:103266. Epub 2020 Dec 17.

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Purpose: Vitamin D (Vit D), as an immunomodulator, has been hypothesized to play a critical role in the pathogenesis of endometriosis. Thus, in this study, we evaluated whether there is an association between 25-hydroxyvitamin D [25(OH)D] and susceptibility to endometriosis in Iranian women.

Methods: Women at reproductive age, including 56 healthy women and 54 patients with endometriosis, were enrolled in the study. Serum levels of 25(OH)D, calcium, parathyroid hormone (PTH), and peritoneal fluid (PF) levels of 25(OH)D were assessed.

Results: The serum and PF levels of 25(OH)D in the patients with endometriosis were significantly lower than the control group (P = 0.001 and P = 0.03, respectively). Subjects with serum levels of 25(OH)D lower than 20 ng/mL had a 2.7 times higher risk of endometriosis than people with 25(OH)D serum levels higher than 20 ng/mL (non-deficient) (OR = 2.7, 95 % confidence interval: 1.24-5.80, P = 0.01). The serum levels of calcium and PTH were significantly lower and higher in patients with endometriosis compared with controls, respectively (P < 0.001, P = 0.02, respectively). Also, the serum levels of 25(OH)D were lower in stages I-II endometriosis than stage III-IV; however, no significant difference was observed.

Conclusion: Our findings showed that people with Vit D deficiency are at higher risk of endometriosis.
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http://dx.doi.org/10.1016/j.jri.2020.103266DOI Listing
February 2021

Resveratrol treatment reduces expression of MCP-1, IL-6, IL-8 and RANTES in endometriotic stromal cells.

J Cell Mol Med 2021 Jan 15;25(2):1116-1127. Epub 2020 Dec 15.

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Endometriosis is an inflammatory disease affecting reproductive-aged women. Immunologic disturbance, as well as inflammation, have crucial roles in the pathogenesis of endometriosis. In this study, we evaluated the effects of resveratrol treatment on expression of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), IL-8, and regulated upon activation, normal T cell expressed and secreted (RANTES) in endometrial stromal cells from patients with endometriosis compared with non-endometriotic controls. Thirteen eutopic (EuESCs) and nine ectopic (EESCs) endometrial stromal cells from endometriotic patients as well as eleven endometrial stromal cells from non-endometriotic controls (CESCs) were treated with resveratrol (100 μmol/L) or ethanol, and gene and/or protein expression of MCP-1, IL-6, IL-8 and RANTES was examined at 6, 24 and 48 hours following treatment in the cells from all origins. Resveratrol treatment significantly reduced gene and protein expression of MCP-1, IL-6, and IL-8 in EuESCs and EESCs compared with CESCs (P < .05-.001, P < .05-.001 and P < .05-<.01, respectively), and this reduction was more noticeable in EESCs than EuESCs (P < .05-<.001). Besides, resveratrol treatment significantly reduced RANTES protein expression in EESCs in all time intervals (P < .05). Resveratrol treatment significantly reduced the expression of MCP-1, IL-6, IL-8 and RANTES in EESCs.
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http://dx.doi.org/10.1111/jcmm.16178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812293PMC
January 2021

Superior hypogastric plexus block as an effective treatment method for endometriosis-related chronic pelvic pain: an open-label pilot clinical trial.

J Obstet Gynaecol 2020 Nov 26:1-6. Epub 2020 Nov 26.

Resident of Anesthesiology, Iran University of Medical Sciences, Tehran, Iran.

We aimed to investigate the effect of superior hypogastric plexus (SHP) block on pain relief and quality of life of patients with refractory endometriosis. Sixteen patients with refractory endometriosis underwent SHP block. The outcome measures included visual analogue scale (VAS) for chronic pelvic pain, VAS for dysmenorrhoea, and VAS for dyspareunia. The short-form endometriosis health profile (EHP-5) was used to measure quality of life. All the outcome measures were evaluated at weeks 0, 1, 4, 12 and 24. The mean baseline VAS scores significantly improved after the SHP block ( < .001 for all). The mean overall EHP-5 score also significantly improved from 54.3 ± 18.2 to 24.6 ± 13.3 ( < .001). The positive effects of SHP were not diminished over time. No serious adverse effect was noticed in any of the patients. Preliminary results suggest that SHP block could be used as an effective method in pain control and improvement of quality of life in refractory endometriosis.IMPACT STATEMENT Safety and efficacy of SHP block in the treatment of CPP has been revealed in earlier investigations. However, the efficacy of SHP block for pain management in patients with refractory endometriosis has not been investigated in earlier investigations. SHP block is an effective method for pain control and improvement of quality of life in patients with refractory endometriosis. The positive effects of this treatment did not diminish over 24-weeks follow-up of the study. No serious adverse effect was noticed in any of the patients. Preliminary results suggest that SHP block could be used safely and effectively for controlling pain and improvement of quality of life in patients with refractory endometriosis.
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http://dx.doi.org/10.1080/01443615.2020.1820468DOI Listing
November 2020

The Effects of Resveratrol Treatment on Bcl-2 and Bax Gene Expression in Endometriotic Compared with Non-Endometriotic Stromal Cells.

Iran J Public Health 2020 Aug;49(8):1546-1554

Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.

Background: We aimed to examine resveratrol effects on gene expression of Bcl-2, Bax and Bcl-2/Bax ratio in endometrial stromal cells derived from women with and without endometriosis.

Methods: Endometrial tissues were obtained from 40 endometriotic patients and 15 non-endometriotic controls undergoing laparoscopic surgery or hysterectomy in the gynecology ward of Rassoul Akram Hospital, Tehran, Iran from 2015 to 2017. After the enzymatic digestion, eutopic (EuESCs) and ectopic (EESCs) endometrial stromal cells from patients with endometriosis as well as endometrial stromal cells from non-endometriotic controls (CESCs) were treated with or without resveratrol (100 μM) and the levels of Bcl-2, Bax and Bcl-2/Bax gene expression ratio in the cells from all origins were examined at 6, 24 and 48 h post-treatment by real-time PCR.

Results: Resveratrol treatment increased Bcl-2 expression in CESCs at 24 and 48 h and in EuESCs at 48 h (<0.05), but had no significant effects on the expression of this gene in EESCs. On the other hand, resveratrol treatment increased Bax expression in EuESCs at 6 h and decreased its expression in EESCs at 48 h (<0.05). Regarding the Bcl-2/Bax gene expression ratio, resveratrol treatment increased Bcl-2/Bax gene expression ratio in CESCs and EuESCs at 48 h (<0.01). However, this treatment had no significant differential effect on Bcl-2 and Bcl-2/Bax gene expression ratio between CESCs and EuESCs at 48 h.

Conclusion: Resveratrol treatment significantly increased Bcl-2/Bax gene expression ratio in EuESCs and CESCs but had no significant effect in EESCs.
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http://dx.doi.org/10.18502/ijph.v49i8.3900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554380PMC
August 2020

The Diagnostic Accuracy of Combined Enolase/Cr, CA125, and CA19-9 in the Detection of Endometriosis.

Biomed Res Int 2020 2;2020:5208279. Epub 2020 Sep 2.

Department of Obstetrics and Gynecology, Kiel School of Gynaecological Endoscopy, University Hospital Schleswig Holstein, Campus Kiel, Arnold-Heller-Str. 3, Haus C, 24105 Kiel, Germany.

Background: The present study was designed to verify the accuracy of the noninvasive biomarkers enolase/Cr, CA125, and CA19-9 as a clinical diagnostic tool for the detection of endometriosis.

Methods: A cross-sectional study was performed at Rasool-e-Akram Hospital affiliated to Iran University of Medical Sciences, Tehran, Iran, from April 2015 to April 2018. Eighty-six women were scheduled to undergo laparoscopy due to chronic pelvic pain, infertility, pelvic mass, and abnormal uterine bleeding. Serum and urine samples of all patients were collected preoperatively. Serum levels of CA125 and CA19-9, and urine levels of enolase-1 were measured. Serum levels of CA125 and CA19-9 were determined by the electrochemiluminescence method (ECL). Urinary enolase-1 was measured by the ELISA method.

Result: Serum levels of CA125 and CA19-9 were significantly higher in the endometriosis group than in controls ( < 0.001, = 0.004, respectively). Levels of enolase I and enolase/Cr were higher in patients with endometriosis, but the differences were not statistically significant. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of combined enolase/Cr, CA125, and CA19-9 were 65%, 66.6%, 71%, and 60.1%, respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of combined enolase/Cr, CA125, and CA19-9 was 1.94 and 0.52, respectively. The area under the ROC curve for enolase/Cr + CA125 + CA19 - 9 was 0.675 (95% confidence interval 0.573-0.710).

Conclusion: The present study revealed that concurrent measurement of enolase-1, CA125, and CA19-9 might be a valuable noninvasive test for the identification of endometriosis.
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http://dx.doi.org/10.1155/2020/5208279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545435PMC
May 2021

Deregulation of Stemness-Related Genes in Endometriotic Mesenchymal Stem Cells: Further Evidence for Self-Renewal/Differentiation Imbalance.

Iran Biomed J 2020 09 18;24(5):333-9. Epub 2020 Apr 18.

Endometriosis Research Center, Iran University of Medical Science, Tehran, Iran.

Background: Any irregularities in self-renewal/differentiation balance in endometriotic mesenchymal stem cells (MSCs) can change their fate and function, resulting in endometriosis development. This study aimed to evaluate the expression of OCT4 transcripts (OCT4A, OCT4B, and OCT4B1), SOX2, and NANOG in endometriotic MSCs to show their aberrant expression and to support self-renewal/differentiation imbalance in these cells.

Methods: MSCs were isolated from three endometriotic and three normal endometrium samples and characterized and analyzed for the expressions of OCT4A, OCT4B, OCT4B1, SOX2, and NANOG using the quantitative real-time PCR.

Results: The expressions of OCT4 transcripts and NANOG increased significantly in endometriotic MSCs, whereas SOX2 expression did not show any significant difference.

Conclusion: Our findings provide further evidence for confirming the self-renewal/ differentiation imbalance in endometriotic MSCs, as the main underlying cause of endometriosis development. This study also paves the way for further research on endometriosis treatment by focusing on endometriotic stem cells.
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http://dx.doi.org/10.29252/ibj.24.5.328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392139PMC
September 2020

Hemoperitoneum due to bleeding from a vein overlying a subserous uterine myoma: a case report.

J Med Case Rep 2020 May 8;14(1):55. Epub 2020 May 8.

Endometriosis Research Center, Rasoul Akram Hospital, Iran University of Medical Science, P.O. Box 1445613131, Tehran, Iran.

Background: Fibroids are the most common pelvic tumors in women; serious complications are rare but can be life-threatening.

Case Presentation: We present a case report of a 38-year-old Persian woman with acute abdominal pain and a history of uterine fibroids. The patient refused to undergo a laparoscopic myomectomy. Her ultrasound examination revealed free fluid in the abdominal cavity, and her vital signs were indicative of vasogenic shock. A diagnostic laparoscopy was performed to identify and control the source of bleeding: 400 ml of blood and blood clots were removed. Active bleeding was seen from a vein overlying a subserosal myoma. A laparotomic myomectomy was performed, and the patient was discharged 3 days after surgery with no complications.

Conclusion: Surgeons should consider the possibility of this complication in women with acute abdominal pain and a history of uterine leiomyoma.
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http://dx.doi.org/10.1186/s13256-020-02383-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210684PMC
May 2020

Evaluating Inhibitory Effects of Paclitaxel and Vitamin D Loaded Poly Lactic Glycolic Acid Co-Delivery Nanoparticles on the Breast Cancer Cell Line.

Adv Pharm Bull 2020 Jan 11;10(1):30-38. Epub 2019 Dec 11.

Urology Research Center, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.

Paclitaxel (PTX) has transpired as a significant agent in the treatment of breast cancer. Meanwhile, polylactic glycolic acid (PLGA) nanoparticles (NPs) are able to increase the anticancer effect of the PTX in the blood. Nano-precipitation was used to prepare the PLGA-PTX-VitD3 co-delivery NPs. Drug loading, encapsulation efficiency, in vitro release profile, cell viability, migration, apoptosis, and bcl2 expression of NPs were evaluated. The average size of co-delivery NPs was 231 ± 46 nm. Observed was a controlled release of the PTX and vitamin D3 from co-delivery NPs between 0.5 and 240 hours. MTT showed the ability of 8 μg.mL-1 of co-delivery NPs to kill 50 % of the MCF-7; likewise, the co-delivery NPs prevented MCF-7 migration. The co-delivery NPs led 46.35 % MCF-7 to enter primary apoptosis. 60.8% of MCF-7 in the control group were able to enter the G (1) phase of the cell cycle. The co-delivery NPs increased expression of bax. In addition to its higher toxicity against MCF-7 than that of PTX, co-delivery NPs were able to release drugs continuously for a long period, which indeed increased the efficiency of the drugs. The effect of co-delivery NPs on MCF-7 cell viability was different from that in other drugs. In fact, the co-deliver NPs were able to release drugs continuously for a long time, this could induce primary apoptosis in the MCF-7 and decrease the metastasis and toxicity of drugs.
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http://dx.doi.org/10.15171/apb.2020.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983998PMC
January 2020

Beneficial Effects of Oral Lactobacillus on Pain Severity in Women Suffering from Endometriosis: A Pilot Placebo-Controlled Randomized Clinical Trial.

Int J Fertil Steril 2019 Oct 14;13(3):178-183. Epub 2019 Jul 14.

Endometriosis Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.

Background: This study assessed the effects of a lactobacillus-based medication on pain intensity scores in women with endometriosis.

Materials And Methods: The present randomized pilot placebo-controlled trial was done on eligible women who were surgically and pathologically diagnosed with endometriosis. Thirty-seven participants who had not received hormonal treatment in the last three months, were enrolled and randomized into LactoFem® and placebo groups. Lactobacillus capsules or placebo were administrated orally once a day for 8 weeks. Patients were assessed for pain severity using Visual Analogue Scale (VAS) scores for dysmenorrhea, dyspareunia and chronic pelvic pain at baseline and after 8 and 12 weeks post-intervention.

Results: Mean age of participants and mean body mass index (BMI) for the LactoFem® and control groups were comparable. All patients had stage 3 and 4 of the disease based on revised American fertility society (AFS) classification of endometriosis. Mean initial pain scores for dysmenorrhea, dyspareunia and chronic pelvic pain were 6.53 ± 2.88, 4.82 ± 3.76 and 4.19 ± 3.53, respectively in the LactoFem® group and 5.60 ± 2.06, 3.67 ± 2.64 and 2.88 ± 2.80, respectively for the control group; the two groups had comparable scores in this regard. There was more decrease in pain scores for both dysmenorrhea and the overall pain after 8 weeks of treatment in LactoFem® group compared to the control group. The scores for dysmenorrhea were 6.53 ± 2.88 and 5.60 ± 2.06 in the LactoFem® and control groups, respectively, before intervention but, after 8-week treatment, these values were 3.07 ± 2.49 and 4.47 ± 2.13 (P=0.018), respectively. The changes in overall pain score in the LactoFem® and control group during this period were 7.33 ± 7.00 and 4.11 ± 1.68, respectively (P=0.017).

Conclusion: This study showed some beneficial effects of lactobacillus administration on endometriosis-related pain (Registration number: IRCT20150819023684N5).
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http://dx.doi.org/10.22074/ijfs.2019.5584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642422PMC
October 2019

Endometrial Preparation for Women Undergoing Embryo Transfer Frozen-Thawed Embryo Transfer With and Without Pretreatment With Gonadotropin Releasing Hormone Agonists.

J Family Reprod Health 2018 Dec;12(4):191-196

Department of Infertility, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

To evaluate the efficacy of endometrial preparation by exogenous steroids, with and without pretreatment by the use of GnRH agonist. This randomized interventional study was conducted on 100 women who underwent a FTET that were randomly assigned to receive GnRH agonist (buserelin) in the luteal phase or no receive this medication. In both groups endometrial preparation was achieved by the use of estradiol valerate pill started from the second day of the menstruation and used every day, with an initial dose of 2mg/d and every 3 days increased to 4 mg/d and 6 mg/d, respectively. Endometrial thickness was evaluated by vaginal ultrasound. Forty eight hours after beginning of progesterone administration 2 to 3 embryos surviving in freezing procedure were transferred. the two groups were similar in mean age, body mass index, duration of infertility, type of infertility, number of embryos transferred and endometrial thickness on the day of beginning progesterone therapy. Comparing outcome of FTET between the two groups scheduled for receiving GnRH agonist showed no significant difference in the rate of implantation (6.7% versus 10.0%), the rate of chemical pregnancy (21.7% versus 22.5%), clinical pregnancy rate (15.0% versus 17.5%), and also ongoing pregnancy (13.3% versus 12.5%). Endometrial preparation for FTET using GnRH agonists appears to be as effective as FTET without administrating these agonists.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581662PMC
December 2018

Resveratrol reduces the expression of insulin-like growth factor-1 and hepatocyte growth factor in stromal cells of women with endometriosis compared with nonendometriotic women.

Phytother Res 2019 Apr 6;33(4):1044-1054. Epub 2019 Mar 6.

Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.

Resveratrol, a phytoalexin polyphenol, has antiproliferative, antiangiogenic, anti-inflammatory, and antioxidant properties. The present study has assessed the effect of resveratrol treatment on the expression of insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) in endometrial stromal cells (ESCs) from women with and without endometriosis. Endometrial tissues were obtained from 40 endometriotic patients and 15 nonendometriotic control women. After the enzymatic digestion, 13 eutopic ESCs (EuESCs), 8 ectopic ESCs (EESCs), and 11 control ESCs (CESCs) were treated with resveratrol (100 μM) for 6, 24, and 48 hr. The gene and protein expressions of IGF-1 and HGF were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay methods, respectively. Results showed that resveratrol treatment decreased significantly the gene expression of IGF-1 and HGF in EuESCs, EESCs, and CESCs (p < 0.05). The effect of resveratrol treatment on the reduction of IGF-1 gene expression was statistically more noticeable in EESCs compared with CESCs (p < 0.05). Also, in the case of HGF gene expression, the reducing effect of resveratrol treatment was statistically more considerable in EESCs compared with EuESCs and CESCs (p < 0.05 and p < 0.01, respectively). The IGF-1 and HGF protein production decreased significantly in EuESCs and EESCs (p < 0.05) but not in CESCs. These findings suggest that resveratrol treatment could reduce the expression of IGF-1 and HGF in ESCs especially in EESCs, which play a pivotal role in disease progression.
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http://dx.doi.org/10.1002/ptr.6298DOI Listing
April 2019

Endometriotic Mesenchymal Stem Cells Epigenetic Pathogenesis: Deregulation of , , and in A Functional Imbalanced Epigenetic Disease.

Cell J 2019 Jul 20;21(2):179-185. Epub 2019 Feb 20.

Endometriosis Research Center, Iran University of Medical Science, Tehran, Iran.

Objective: Stem cell issue is a strong theory in endometriosis pathogenesis. It seems that endometriotic mesenchymal stem cells (MSCs) show different characteristics compared to the normal MSCs. Determined high proliferation and low differentiation/decidualization potential of endometriotic MSCs could be accompanied by their microRNAs deregulation influencing their fate and function. In this study for the first time, we evaluated the expression of , , and in endometriotic compared to non-endometriotic MSCs. These microRNAs are involved in biological pathways related to proliferation and differentiation of stem cells. Their aberrant expressions can disturb the proliferation/ differentiation balance in stem cells, altering their function and causing various diseases, like endometriosis.

Materials And Methods: In this experimental study, MSCs were isolated from three endometriotic and three nonendometriotic eutopic endometrium, followed by their characterization and culture. Expression of , , and was ultimately analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results: We found that the expression of was up-regulated (P<0.0001) whereas the expression of and was down-regulated (P<0.0001) in endometriotic MSCs in comparison with non-endometriotic normal controls.

Conclusion: Proliferation and differentiation are important dynamic balanced biological processes, while in equillibrium, they determine a healthy stem cell fate. It seems that they are deregulated in endometriotic MSCs and change their function. , , and are deregulated during endometriosis and they have pivotal roles in the modulating proliferation and differentiation of stem cells. We found up-regulation of and down-regulation of and in endometriotic MSCs. These changes can increase self-renewal and migration, while decreasing differentiation of endometriotic MSCs. Our achievements emphasize previous findings on the importance of proliferation/ differentiation balance in MSCs and clarify the role of microRNAs as main players in faulty endometriotic stem cells development.
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http://dx.doi.org/10.22074/cellj.2019.5903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397607PMC
July 2019

Differentiation of human mesenchymal stem cells (MSC) to dopaminergic neurons: A comparison between Wharton's Jelly and olfactory mucosa as sources of MSCs.

J Chem Neuroanat 2019 03 10;96:126-133. Epub 2019 Jan 10.

Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran. Electronic address:

The generation of dopaminergic neurons from stem cells is a potential therapeutic approach to treat neurodegenerative disorders, such as Parkinson's disease. The current study aims to investigate the potential of two different types of mesenchymal stem cells derived from human Wharton's jelly and nasal cavity for differentiation into dopaminergic neurons. The differentiation capacities of both cell types were evaluated using real-time PCR, immunocytochemistry, flow cytometry and HPLC. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are noted for their capability to differentiate into mesodermal and non-mesodermal cells, including neurons. However, it was demonstrated that having the same neuroectodermal origin as the nervous system, the olfactory ectomesenchymal stem cells (OE-MSCs) expressed the neural marker MAP2 as well as dopaminergic markers such as tyrosine hydroxylase (TH), dopamine transporter (DAT) and PITX3 to a greater extent than the WJ-MSCs both at the level of mRNA and protein. Furthermore, quantitative flow cytometric evaluation of these markers at 12 days post-induction supported the above-mentioned results. Finally, the assessment of the functionality of differentiated cells and their ability to synthesize dopamine measured by HPLC revealed that the OE-MSC-derived dopaminergic cells released almost the same amount of dopamine as that secreted by WJ-MSC-derived cells. Thus it showed the difference in their functionality to be negligible. Overall, it may be concluded that higher proliferation and differentiation capacity of OE-MSCs, along with their easier harvestability and autologous transplantability compared with WJ-MSCs, makes them a better cell source for stem cell therapy of neurodegenerative disorders which are caused by degeneration of dopaminergic neurons.
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http://dx.doi.org/10.1016/j.jchemneu.2019.01.003DOI Listing
March 2019

Adnexal mass with extremely high levels of CA-125 and CA19-9 but normal Human Epididymis Protein 4 (HE4) and Risk of Ovarian Malignancy Algorithm (ROMA): Endometriosis or ovarian malignancy? A case report.

Int J Reprod Biomed 2018 Jun;16(6):413-416

Endometriosis Research Center, Department of Obstetrics and Gynecology, Iran University of Medical Sciences (IUMS), Tehran, Iran.

Background: It has been shown that Carbohydrate antigen (CA) 125 and CA 19-9 tumor markers are useful for diagnosis and follow up of ovarian carcinoma.

Case: In this case, we reported the high level of CA-125 and CA 19-9 with large right ovarian intact endometrioma and extensive involvement of omentum.

Conclusion: Human Epididymis protein (HE4) and Risk of ovarian malignancy algorithm (ROMA) can be useful in differentiation between malignancies and benign pathologies with a good sensitivity and specificity value.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079310PMC
June 2018

Conservative Management of Ovarian Fibroma in A Case of Gorlin-Goltz Syndrome Comorbid with Endometriosis.

Int J Fertil Steril 2018 Apr 15;12(1):88-90. Epub 2018 Jan 15.

Endometriosis Research Center, Iran University of Medical Science, Tehran, Iran.

Ovarian fibromas are the most common benign solid ovarian tumors, which are often difficult to diagnose preoperatively. Ovarian fibromas, especially in bilateral cases, may be cases of Gorlin-Goltz syndrome (GGS), a rare autosomal dominant disorder with predisposition to basal cell carcinomas (BCCs) and other various benign and malignant tumors. This case report describes a 25 year-old female with GGS, bilateral ovarian fibroma, endometriosis and septated uterus, which was referred to the Gynecology Clinic of Rasoul-e-Akram Hospital in October 2016. This patient had facial asymmetry due to recurrent odontogenic keratocysts. In young cases of ovarian fibromas as reported here, conservative surgical management can preserve ovarian function and fertility. These patients must be followed up by a multidisciplinary team and submitted to periodic tests.
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http://dx.doi.org/10.22074/ijfs.2018.5240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767939PMC
April 2018

Effects of Vitamin D on Endometriosis-Related Pain: A Double-Blind Clinical Trial.

Med Sci Monit 2016 Dec 17;22:4960-4966. Epub 2016 Dec 17.

Department of Endoscopic Surgery, Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran.

BACKGROUND Endometriosis is a disabling disease of reproductive-age women. Dysmenorrhea, dyspareunia, and pelvic pain are the main symptoms of endometriosis. Its etiology is not clear. Endometriosis may have various causes, including vitamin D deficiency, but its effect is controversial. MATERIAL AND METHODS In this double-blind clinical trial, we enrolled patients with endometriosis diagnosed and treated by laparoscopy, with scores of at least 3 for of dysmenorrhea and/or pelvic pain at 8 weeks after surgical treatment. They were randomly prescribed vitamin D (50 000 IU weekly for 12 weeks) or placebo. Severity of pain in the 2 groups (placebo and treatment) was compared by VAS test at 24 weeks after surgical treatment. RESULTS There were 19 patients in the vitamin D group and 20 in the placebo group. Baseline characteristics in the 2 groups were similar. Following the treatment with vitamin D or placebo, we did not find significant differences in severity of pelvic pain (p=0.24) and dysmenorrhea (p=0.45) between the 2 groups. Mean pelvic pain at 24 weeks after laparoscopy in the vitamin D group was 0.84±1.74 and in placebo group it was 0.68±1.70 (p=0.513). Mean dysmenorrhea was 2.10±2.33 in the vitamin D group and 2.73±2.84 in the placebo group (p=0.45). CONCLUSIONS After ablative surgery for endometriosis, vitamin D treatment did not have a significant effect in reducing dysmenorrhea and/or pelvic pain.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5189720PMC
http://dx.doi.org/10.12659/msm.901838DOI Listing
December 2016

Outcomes of assisted reproduction treatment after dopamine agonist -cabergoline- for prevention of ovarian hyper stimulation syndrome.

Med J Islam Repub Iran 2016 17;30:371. Epub 2016 May 17.

Master in Clinical Laboratory Sciences, Department of Infertility of Shariati hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: Release of vascular endothelial growth factor (VEGF) by ovaries in response to HCG administration is one of the main mechanisms of ovarian hyper stimulation syndrome. Since Dopamine/dopamine receptor2 (Dp-r2) pathway activity -mediated by VEGF/ Vascular endothelial growth factor receptor 2 (VEGFR- 2) signaling-, is associated with angiogenic events, dopamine agonists were used for the management of severe forms of OHSS. In order to assess the effects of Cabergoline on angiogenesis in the human endometrium, and subsequently its impacts on the implantation rate this study was conducted.

Methods: This historical cohort study was conducted based on existing data of 115 patients (20-40 years) whom underwent assisted reproductive treatment (ART) and with a high probability for developing OHSS between March 2007 and September 2008. Forty five cases received Cabergoline were compared to 70 control subjects. The statistical methods used were: Unpaired t-test for continuous variables and the chi-square test (or Fisher's exact test if required) for categorical variables.

Results: None of the patients (treatment or control group) developed OHSS. The etiologies of infertility and administration of GnRH agonist or antagonist protocols were similar in two groups (p>0.2). Number of transferred embryos and zygote intra-fallopian transfer (ZIFT) did not differ between the two groups (p≥0.06). Implantation rate in treatment (3.1%) and control (6.6%) subjects was similar (p=0.4). No significant difference was observed in fertilization rate, chemical, clinical and ongoing pregnancies between the two groups (p>0.5).

Conclusion: Cabergoline can be safely administered in ART protocols to prevent OHSS, without compromising ART outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972057PMC
August 2016

An Introduction to The Royan Human Ovarian Tissue Bank.

Int J Fertil Steril 2016 Jul-Sep;10(2):261-3. Epub 2016 Jun 1.

Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran; Department of Anatomy, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

From December 2000 until 2010, the researchers at Royan Institute conducted a wide range of investigations on ovarian tissue cryopreservation with the intent to provide fertility pres- ervation to cancer patients that were considered to be candidates for these services. In 2010, Royan Institute established the Royan Human Ovarian Tissue Bank as a subgroup of the Embryology Department. Since its inception, approximately 180 patients between the ages of 747 years have undergone consultations. Ovarian samples were cryopreserved from 47 patients (age: 7-35 years) diagnosed with cervical adenocarcinoma (n=9); breast carcinoma (n=7), Ewing's sarcoma (n=7), opposite side ovarian tumor (n=7), endometrial adenocarci- noma (n=4), malignant colon tumors (n=3), as well as Hodgkin's lymphoma, major thalas- semia and acute lymphoblastic leukemia (n=1-2 patients for each disease). Additionally, two patients requested ovarian tissue transplantation after completion of their treatments.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948080PMC
http://dx.doi.org/10.22074/ijfs.2016.4918DOI Listing
July 2016

A Case of Colorectal Cancer during Pregnancy: A Brief Review of the Literature.

Case Rep Obstet Gynecol 2013 14;2013:626393. Epub 2013 Jan 14.

Research Development Center, Shariati Hospital, Tehran University of Medical Sciences, P.O. Box 14155-6447, Tehran, Iran.

The incidence of colorectal cancer (CRC) during pregnancy is so rare. Herein we present a case of colorectal cancer that was missed by pregnancy all over the pregnancy period. The patient was a 37-year-old woman (gravid 4, para 2) referred with the complaints of vaginal discharge and suspicious rupture of membrane (ROM). The patient was pale and the initial physical examination revealed dilation of two fingers, effacement about 30%. She underwent emergent cesarean section which showed adhesions surrounding the uterus, the bladder, and the abdominal wall. Forty days postoperatively, the patient presented with abdominal pain in the left upper quadrant (LUQ). Imaging confirmed a mass in LUQ. Partial colectomy of transverse colon (20 cm) was performed. Postoperative histopathologic study revealed a 7 ∗ 6 ∗ 5 cm mass in transverse colon compatible to stage IIa of the Duck class (T3, N0, Mx). Adjuvant chemotherapy was applied and the patient showed improvements during 7 months followup after surgery. Colorectal cancer in pregnancy is associated with diagnostic and therapeutic challenges which mostly lead to late diagnosis in advanced stages and poor prognosis. A targeted program to improve the general population knowledge and the establishment of a national consultant and screening program particularly for women with a planned pregnancy in the high risk group might be beneficial.
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http://dx.doi.org/10.1155/2013/626393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557611PMC
February 2013

Estradiol supplementation during the luteal phase in poor responder patients undergoing in vitro fertilization: a randomized clinical trial.

J Assist Reprod Genet 2011 Sep 1;28(9):785-90. Epub 2011 Jul 1.

Department of Infertility, Zanjan University of Medical Sciences, North Karegar Street, Zanjan, Iran.

Purpose: This study was designed to evaluate the effects of adding Estradiol (E2) supplementation to progesterone (P) on improvement of pregnancy outcomes in poor responder patients who underwent in vitro fertilization (IVF).

Methods: In a prospective randomized clinical trial, 118 poor responder patients, older than 38 years without contraindications of estradiol consumption from Infertility clinic of a university hospital were randomly divided (by computerized software) into two groups. Control group (59 patients) received only P and intervention group (59 patients) received P and E2 (4 mg/d). Supplementation was done with 4 mg E2 in the luteal phase. Fertilization rate, implantation rate, biochemical and clinical pregnancy rates, abortion rate, ongoing pregnancy, multiple pregnancy and ectopic pregnancy rates were documented for those who completed the study protocol in each group (per protocol analysis) and compared between groups.

Result: Fifty five patients in control group and 53 patients in intervention group successfully completed the study protocol. Treatment outcomes were not significantly different between two groups.

Conclusion: For poor responder women who underwent IVF, addition of E2 to P supplementation could not significantly improve pregnancy outcomes.
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http://dx.doi.org/10.1007/s10815-011-9595-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3169685PMC
September 2011