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.

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.

Methyltetrahydrofolate vs Folic Acid Supplementation in Idiopathic Recurrent Miscarriage with Respect to Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms: A Randomized Controlled Trial.

PURPOSE: To determine whether 5-methylenetetrahydrofolate (MTHF) is more effective than folic acid supplementation in treatment of recurrent abortion in different MTHFR gene C677T and A1298C polymorphisms. METHODS: A randomized, double blind, placebo-controlled trial conducted April 2011-September 2014 in recurrent abortion clinics in Tehran, Iran. The participants were women with three or more idiopathic recurrent abortion, aged 20 to 45 years. Two hundred and twenty eligible women who consented to participate were randomly assigned to receive either folic acid or 5-MTHF according to the stratified blocked randomization by age and the number of previous abortions. Participants took daily 1 mg 5-methylentetrahydrofolate or 1 mg folic acid from at least 8 weeks before conception to the 20th week of the pregnancy. The primary outcome was ongoing pregnancy rate at 20th week of pregnancy, and the secondary outcomes were serum folate and homocysteine at the baseline, after 8 weeks, and at the gestational age of 4, 8, 12, and 20 weeks, MTHFR gene C677T and A1298C polymorphisms. RESULTS: There was no significant difference in abortion rate between two groups. Serum folate increased significantly in both groups over time; these changes were significantly higher in the group receiving 5-MTHF than the group receiving folic acid (value = 2.39, p<00.1) and the result was the same by considering the time (value = 1.24, p<0.01). Plasma tHcys decreased significantly in both groups over time; however these changes were not significantly different between the groups (value = 0.01, p = 0.47). CONCLUSION: The results do not support any beneficial effect of 5-MTHF vs. folate supplementation in women with recurrent abortion with any MTHFR C677T and/or A1298C polymorphism. TRIAL REGISTRATION: ClinicalTrials.gov NCT01976676.