The effect of Myo-Inositol supplement on molecular regulation of folliculogenesis, steroidogenesis, and assisted reproductive technique outcomes in patients with polycystic ovarian syndrome.

RESEARCH QUESTION: The mechanism of Myo-Inositol, as an adjuvant, on key signaling pathways related to oocyte maturation, fertilization rate, and embryo quality as well as ovarian steroidogenesis in cumulus cells of PCOS patients, is still unclear. DESIGN: Infertile patients who were candidates for ART cycles were divided into three groups (n = 30 in each group), including group 1: PCOS patients only receiving folic acid, group 2: PCOS patients receiving daily Myo-Inositol combined with folic acid, and a control group (group 3): normal ovulatory women without PCOS receiving only folic acid from 1 month prior to IVF cycle until the day of ovum pick up. During the ART procedure, oocytes maturation, fertilization rate, and embryo quality were assessed. The gene expressions of FSHR, LHR, CYP11A1, CYP19A1, 3ß-HSD2, and StAR were also analyzed using qRT-PCR. Western blot analysis was performed for the evaluation of AKT, ERK, CREB, and AMPK phosphorylation. RESULT: Despite equal number of retrieved oocytes, the percentages of MII oocytes, fertilization rate, and embryo quality were found to be significantly higher in group 2 due to the administration of inofolic. The expressions of all the studied genes were significantly higher in the cumulus cells of group 1 compared to the group 2. Higher phosphorylation of ERK1/2 was found in the groups 2 and 3 compared to the group 1. On the other hand, p-Akt has significantly decreased in the group 2 compared to the group 1. CONCLUSION: Our study provides new insight into the molecular mechanism underlying the positive effect of Myo-Inositol on intrinsic ovarian defects in PCOS, steroidogenesis, oocyte maturation, fertilization rate, and embryo quality.

The myo-inositol effect on the oocyte quality and fertilization rate among women with polycystic ovary syndrome undergoing assisted reproductive technology cycles: a randomized clinical trial.

PURPOSE: The aim of the present study was to evaluate the effect of myo-Inositol administration on oocyte quality, fertilization rate and embryo quality in patients with PCOS during assisted reproductive technology (ART) cycles. METHODS: Fifty infertile PCOS patients were randomly designated in two groups. In the study group, patients received daily doses of 4 g myo-Inositol combined with 400 mg folic acid and in the control group patients received only 400 mg folic acid from 1 month before starting the antagonist cycle until the day of ovum pick up. Oocyte and embryo qualities were assessed according to European Society of Human Reproduction and Embryology (ESHRE) guidelines. The gene expression of PGK1, RGS2 and CDC42 as a factor of oocyte quality in granulosa cells was analyzed using real-time RT-PCR. Levels of total antioxidant capacity (TAC) and reactive oxygen species (ROS) were evaluated by chemiluminescence assay in follicular fluid. RESULTS: The percentage of metaphase II oocyte, fertilization rate and embryo quality significantly improved in the study group (p < 0.05), but the number of retrieved oocytes and follicle count were not statistically different between groups. Furthermore, the gene expression of PGK1, RGS2 and CDC42 was significantly higher in the study group (p < 0.05) but no differences were found between two groups in terms of TAC and ROS levels. CONCLUSIONS: The present study findings suggest that myo-Inositol alters the gene expression in granulosa cells and improves oocyte and embryo quality among PCOS patients undergoing ART.

The effects of CA1 5HT4 receptors in MK801-induced amnesia and hyperlocomotion.

In this study, the effects of 5-HT4 receptors of the CA1 on MK801-induced amnesia and hyperlocomotion were examined. One-trial step-down method was used to assess memory retention and then, the hole-board method to assess exploratory behaviors. The results showed that post-training intra-CA1 administration of RS67333 (62.5 and 625 ng/mouse) and RS23597 (1 and 10 ng/mouse) decreased memory consolidation, but it did not alter head-dip counts, head-dip latency and locomotor activity. Similarly, MK801 (0.5 and 1 µg/mouse) decreased memory consolidation, but had no effect on head-dip counts and head-dip latency. Interestingly, it increased locomotor activity. The results also showed that post-training intra-CA1 injection of a sub-threshold dose of RS67333 (6.25 ng/mouse) or RS23597 (0.1 ng/mouse) could heighten MK801 induced amnesia and decrease locomotor activity, but it did not alter head-dip counts and head-dip latency. In conclusion, our findings suggest that the CA1 5-HT4 receptors are involved in MK801-induced amnesia and hyperlocomotion.