To some extent, the use of metformin may improve endometrial receptivity and pregnancy outcomes of women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection. However, the mechanism is not well-known. The endometrium of metformin-treated group (metformin-treated patients with PCOS) and the control group (non-metformin-treated patients with PCOS) were analyzed for the expression of homeobox A10 (HOXA10) and integrin beta-3 (ITGB3) and differential micro RNA (miRNA) expression profiles. On this basis, miRDB and Target Scan databases were used to predict and screen out that miR-491-3p and miR-1910-3p may target HOXA10 and ITGB3. Furthermore, we verified the effects of metformin on the expression of HOXA10 and ITGB3, and regulatory effects of miR-1910-3p and miR-491-3p on HOXA10 and ITGB3 using Ishikawa cell line. Metformin induced a significant dose-dependent upregulation of HOXA10 and ITGB3. The results from the microarray analyses showed there were 40 differentially expressed miRNAs between the 2 groups. Among them, miR-1910-3p and miR-491-3p were the 2 significantly downregulated miRNAs. Bioinformatics prediction indicated that HOXA10 and ITGB3 are potential target genes for miR-1910-3p and miR-491-3p. In Ishikawa cells transfected with miR-491-3p mimics, the expression of HOXA10 and ITGB3 on both messenger RNA (mRNA) and protein level were lower than those in control group ( P < .001). Also, the expression of HOXA10 mRNA and protein was lower in Ishikawa cells transfected with miR-1910-3p mimics ( P < .001). However, no significant changes in ITGB3 levels were observed in cells transfected with miR-1910-3p mimics ( P > .05). Metformin likely improves endometrial receptivity through downregulating the expression of miR-491-3p and miR-1910-3p, thereby increasing the expression of HOXA10 and ITGB3 in the endometrium of PCOS women.

Background Studies have shown that abnormalities in the decidualization process were closely related to recurrent implantation failure (RIF). Prokineticin 2 (PK2) is a secreted protein with angiogenic and tissue remodeling functions but its role in the endometrium is unknown. Methods PK2 levels and its receptor PKR1 mRNA and protein levels in mid-secretory endometrium from normal and RIF women were examined by real-time PCR and western blotting, respectively. The effects of PK2 were evaluated by overexpressed PK2 in immortalized endometrial T-HESC cells using lentivirus vector and found different expression of Matrix metalloproteinase 9(MMP9) and lncRNA LUCAT1 by RNA-sequencing. The ability of PK2 to regulate LUCAT1 and MMP9 was verified in endometrial cells by real-time PCR and western blotting. Results Using endometrial biopsies from normal and RIF patients, we found increased expression of PK2, together with its receptor PKR1 in RIF patients. We then overexpressed PK2 in immortalized endometrial T-HESC cells using lentivirus vector and found decreased expression of Matrix metalloproteinase 9(MMP9), and increased expression of lncRNA LUCAT1. We verified the ability of PK2 to stimulate LUCAT1 and decrease MMP9 in endometrial cells. We further demonstrated that increased expression of a long noncoding RNA LUCAT1 and decreased expression of MMP9 in endometrial biopsies of patients with RIF. Thus, we highlighted the important role of PK2 and its receptor PKR1 in decidualization and RIF. Conclusion Prokineticin 2 and its receptor are important in endometrium decidualization. PK2 may affect endometrial decidualization through the LUCAT1- MMP9 pathway, thereby affecting embryo implantation.

OBJECTIVE: To characterize exercise behavior of patients with polycystic ovary syndrome (PCOS) by ethnicity. DESIGN: This was a cross-sectional assessment of women who attended a multidisciplinary PCOS clinic. MATERIALS AND METHODS: Participants were recruited consecutively from 2006-2018 from a PCOS specialty clinic at a tertiary academic institution and systematically evaluated for demographic and anthropometric data. Exercise data were ascertained by the validated International Physical Activity Questionnaire, from which we calculated metabolic equivalents (METs) as the unit of energy expenditure. Threshold for adequate physical activity was defined by the guidelines published by the US Department of Health and Human Services (DHHS), either as 150 minutes a week of moderate-intensity, or 75 minutes a week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate-and vigorous-intensity aerobic activity. Patients were divided into three groups based on their self-reported ethnicity (White, Hispanic, or East/Southeast Asian). Statistical analysis was performed with SAS 9.4, 32-bit edition. All testing was performed at the 0.05 level of significance. RESULTS: Of the 375 women evaluated, 71.7% (n ¼ 269) were White, 17.6% (n ¼ 66) were Hispanic, and 10.7% (n ¼ 40) were East/Southeast (SE) Asian. The study population was notable for Hispanic patients having higher BMI (p < 0.01) and waist circumference (p < 0.01). Analysis of exercise data revealed differences in mean METs from vigorous activity (MET vig) as well as mean total METs (moderate plus vigorous activity (MET total)) between the 3 groups. These differences approach, but do not reach, statistical significance when controlled for age (p ¼ 0.08 for MET vig and p ¼ 0.12 for MET total). This trend is mainly attributed to differences in MET vig and MET total between East/SE Asian and White patients (paired p-values of 0.16 and 0.15, respectively), where East/SE Asian patients have less MET vig and MET total. The three ethnic groups also differ significantly in frequency of meeting threshold for adequate physical activity (p ¼ 0.03). Hispanic patients were observed to be more likely to have inadequate physical activity compared to White patients (paired odds ratio of 1.58; 95% CI [1.04, 2.41], p ¼ 0.03). CONCLUSIONS: We observed a trend for East/Southeast Asian patients to achieve the least amount of average metabolic equivalents from both vigorous activity and overall physical activity. Additionally, Hispanic patients were noted to be less likely to have adequate physical activity using a threshold approach. These observations could guide providers in delivering targeted counseling and encouragement when caring for PCOS patients from different backgrounds.

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