In polycystic ovary syndrome (PCOS), substantial genetic and environmental alterations, along with hyperandrogenism, affect the quality of oocytes and decrease ovulation rates. To determine the mechanisms underlying these alterations caused specifically by an increase in plasma androgens, the present study was performed in experimentally-induced PCOS mice. As the study model, female B6D2F1 mice were treated with dehydroepiandrosterone (DHEA, 6mg per 100g bodyweight). After 20 days, oocytes at the germinal vesicle and metaphase II stages were retrieved from isolated ovaries and subsequent analyses of oocyte quality were performed for each mouse. DHEA treatment resulted in excessive abnormal morphology and decreased polar body extrusion rates in oocytes, and was associated with an increase in oxidative stress. Analysis of fluorescence intensity revealed a significant reduction of DNA methylation and dimethylation of histone H3 at lysine 9 (H3K9) in DHEA-treated oocytes, which was associated with increased acetylation of H4K12. Similarly, mRNA expression of DNA methyltransferase-1 and histone deacetylase-1 was significantly decreased in DHEA-treated mice. There was a significant correlation between excessive reactive oxygen species (ROS) production and increased histone acetylation, which is a novel finding and may provide new insights into the mechanism causing PCOS. The results of the present study indicate that epigenetic modifications of oocytes possibly affect the quality of maturation and ovulation rates in PCOS, and that the likely mechanism may be augmentation of intracytoplasmic ROS.

PurposeDiabetic peripheral neuropathic pain (DPNP) is one of the most sufferings, disabling, and dominant complications of diabetes. Duloxetine (DLX) and Pregabalin (PGB) are among first-line therapy and the most prescribed drugs for DPNP relief. The effectiveness-risk profile of drugs may differ from region to region due to variations in genetic and health situation of populations. This study aims to evaluate the efficacy and safety of DLX and PGB in a sample of Iranian population with DPNP.MethodsA double-blind, randomized clinical trial was conducted on 180 type-2 diabetic patients with DPNP≥40 mm according to Visual Analogue Scale (VAS), with other eligibility criteria throughout twelve weeks. We divided the patients randomly into two equal groups: DLX and PGB. Each patient received ten days placebo as a washout period, then blind capsules of DLX (group 1) or PGB (group 2). We assessed the efficacy and safety of drugs by VAS and recorded the Adverse Drug Reactions (ADRs) during the study.ResultsIn the DLX group, sixty-six and the PGB group, seventy-eight patients completed the study. The intensity of patients’ pain was improved by both drugs significantly (p˂0.001), but there was no significant difference between the two groups. Average daily doses of DLX and PGB were 42.5 and 235.5 mg, respectively. In the DLX group, 74% of patients and the PGB group, 37% reported ADRs. The discontinuation rates due to ADRs were 19% and 7% correspondingly.ConclusionWe found that in Iranian patients, the mean effective doses of these drugs are different in comparison with several other studies. Surprisingly intolerance and discontinuation of DLX in our patients were attributed to mild and severe Serotonin Syndrome, which had not much occurred in other studies. Accordingly, despite the same efficacy, PGB was better tolerated than DLX in our patients. Thus we would recommend PGB for DPNP treatment in Iranian patients.

Results of our study showed that using therapeutic lasers with green, blue, red, and infrared wavelengths may accelerate healing process. This trend is more obvious in red and infrared groups especially after acute phase, however, this effect was neither statistically nor clinically significant.

No abstract

Although in‐vitro maturation (IVM) of oocytes has been presented as an alternative treatment to traditional stimulated in‐vitro fertilization, the culture condition can be improved by natural antioxidants. Thus, we investigated the protective effect of Thymoquinone (TQ) during IVM in the polycystic ovary syndrome (PCOS) mice model. The induction of PCOS was made by dehydroepiandrosterone via subcutaneous injection, in prepubertal female B6D2F1‐mice. After 21 days later, germinal vesicle (GV)‐stage‐oocytes were extracted and incubated in IVM media containing 0, 1.0, 10.0, and 100.0 μM of TQ. To assess fertilization and blastulation rates, after 22–24 hr, the treated oocytes were fertilized in‐vitro with epididymal spermatozoa. Some other oocytes were evaluated for maturation, epigenetic, and oxidative stress markers. Similarly, the mRNA expression of epigenetic enzymes genes (Dnmt1 and Hdac1), three maternally derived genes (Mapk, CyclinB, and Cdk1) and apoptosis‐related genes (Bax and Bcl2) were assessed. Our results showed that the maturation, fertilization, and blastulation rates were significantly higher in the 10.0 μM TQ‐treated group compared with the untreated group and likewise with in‐vivo matured oocytes. The Bax expression was reduced in 10.0 μM TQ matured oocytes, but Bcl2, Dnmt1, Hdac1, Cdk1, and Mapk were upregulated in this group compared to other groups. Furthermore, dimethylation of histone‐3 at lysine‐9 (H3K9m2) and DNA methylation were significantly increased whereas H4K12 acetylation (H4K12ac) was decreased in the 10.0 μM TQ‐treated group in comparison with control and in‐vivo matured oocytes. Therefore, our results are suggesting that 10.0 μM TQ may enhance the developmental competence of PCOS oocytes via the modulation of oxidative stress and epigenetic alterations.