hsa_circ_001946 elevates HOXA10 expression and promotes the development of endometrial receptivity via sponging miR-135b.

BACKGROUND: Impaired endometrial receptivity is a major reason for embryo implantation failure. There's a paucity of information regarding the role of circRNAs on endometrial receptivity. Here, we investigated the function of hsa_circ_001946 on endometrial receptivity and its mechanisms. METHODS: A total of 50 women composing 25 with recurrent implantation failure and 25 who conceived after their implantation were recruited in this study. Expression of hsa_circ_001946, miR-135b, and HOXA10 was evaluated by quantitative RT-PCR (qRT-PCR) in biopsied endometrial tissue samples. The levels of HOXA10, and cell cycle markers (CCNB1, CDK1, and CCND1) were determined by IHC and western blotting assays. Binding relationship among miR-135b, hsa_circ_001946 and HOXA10 were confirmed by dual luciferase reporter assays and western blotting. MTT assays and cell cycle assays by FACS were employed to evaluate the proliferation and cell cycle of cells. T-HESCs were cultured with 1 µM medroxyprogesterone acetate (MPA) and 0.5 mM 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP) to induce decidualization. The mechanisms and functions of hsa_circ_001946 on decidualization were further assessed by qRT-PCR evaluating the expression of hsa_circ_001946, miR-135b, HOXA10 and decidual markers (PRL and IGFBP1) in T-HESCs. RESULTS: Endometrial tissues from patients with recurrent implantation failure had lower hsa_circ_001946 expression, higher miR-135b expression, and lower HOXA10 expression. Hsa_circ_001946 promoted HOXA10 expression by sponging miR-135b in T-HESCs. Overexpression of hsa_circ_001946 restored cell proliferation and cell cycle that were disrupted by miR-135b overexpression in T-HESCs. Decidualized T-HESCs had higher hsa_circ_001946 expression, lower miR-135b expression, and higher HOXA10 expression. Overexpression of hsa_circ_001946 reversed the expression of decidual markers (PRL and IGFBP1) that were suppressed by miR-135b overexpression in T-HESCs. CONCLUSIONS: In conclusion, our findings suggest that hsa_circ_001946 promotes cell proliferation and cell cycle process and increases expression of decidualization markers to enhance endometrial receptivity progression via sponging miR-135b and elevating HOXA10.

Association Between Body Mass Index and Male Sperm Apoptosis and Apoptosis-Related Factors.

BACKGROUND: Although obesity may affect reproductive functions, the molecular mechanisms of apoptosis-related biomarkers remain uncertain. OBJECTIVE: To examine the effects of body mass index on sperm quality and apoptosis-related factors in seminal plasma of men. METHODS: Data for 54 subfertile men were collected at our reproductive medical center. The men were divided into normal weight, overweight, and obese groups based on their body mass index (BMI). Sperm DNA fragmentation (sperm chromatin structure analysis), sperm apoptosis (annexin V), and sperm apoptosis-related factors (antibody array assay) were assessed and their relationships with BMI were analyzed. RESULTS: BMI was not significantly related to age, duration of infertility, duration of sexual abstinence, semen volume, sperm concentration, or rate of normal sperm morphology (p > 0.05). However, progressive sperm motility was significantly reduced and the rates of sperm DNA fragmentation index (DFI) and sperm apoptosis were significantly increased in overweight and obese men compared with men with normal BMI. Fas/Fasl, Bcl-2/Bax, caspase-3, caspase-8, p53, and p21 were all upregulated in the overweight and obese groups. Protein function annotation by Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that apoptosis-related factors were enriched in a network associated with activation of apoptotic signaling pathways, such as apoptosis and p53 signaling. CONCLUSION: These data suggest that increased BMI is associated with increased sperm apoptosis and sperm DNA damage, as well as accelerated expression of apoptosis-related factors via the activation of apoptotic signaling pathways.