Association of rs1570360 and rs2010963 in VEGF and rs2279744 in the MDM2 gene with Recurrent Implantation Failure in Iranian Women.

OBJECTIVE: The embryo implantation includes a complex sequence of signaling events, comprising numerous molecular mediators, such as ovarian hormones, cytokines, adhesion molecules and, growth factors. One of the critical factors in angiogenesis is the vascular endothelial growth factor (VEGF). The VEGF plays a pivotal role in embryonic development, decidua vascularization and placental angiogenesis. Furthermore, the P53 gene and its negative regulator, murine double minute 2 (MDM2), are major players in reproductive processes. This study aimed to assess the association of polymorphisms of the VEGF and the MDM2 genes with idiopathic recurrent implantation failure. METHODS: We genotyped 60 women with previous idiopathic recurrent implantation failures and 60 fertile women as controls. Restriction Fragment Length Polymorphism (RFLP) and Sanger sequencing were used for genotyping the rs2010963 and the rs1570360 polymorphisms in VEGF; and the rs2279744 in MDM2 genes. RESULTS: Results indicated a higher frequency of the VEGF rs1570360 AA genotype and A allele in patients with a history of idiopathic implantation failure [OR=6.4 (1.22 - 33.64), p-value=0.02)]. However, the frequency of VEGF +405 G/C and MDM2 SNP309 T/G [(OR=3 (0.5 - 16) p-value=0.2, OR=1.18 (0.3 - 3.7) p-value=0.7, respectively)] genotypes were not significantly different between cases and controls. CONCLUSIONS: The VEGF polymorphism may influence embryo implantation and the VEGF rs1570360 AA genotype may predispose to the risk of recurrent implantation failure after IVF.

Probabilistic non-carcinogenic and carcinogenic risk assessments (Monte Carlo simulation method) of the measured acrylamide content in Tah-dig using QuEChERS extraction and UHPLC-MS/MS.

A modified "Quick, Easy, Cheap, Effective, Rugged, and Safe" QuEChERS in combination with Ultra-High Performance Liquid Chromatography/tandem mass spectrometry (UHPLC-MS/MS) method was optimized for the determination of acrylamide content in different types of tah-dig (rice, bread, and potato). Also, the non-carcinogenic and carcinogenic risks (target hazard quotient (THQ) and incremental lifetime cancer risk (ILCR)) due to ingestion of acrylamide via tah-dig in the adults and children were assessed by Monte Carlo simulation (MCS) method. The recoveries of acrylamide at five concentration levels (n = 3) ranged from 83.82% to 106.41%. The repeatability of the proposed method was demonstrated with RSD% in the range of 11.3-20%. In addition, the limits of detection and quantification were reported as 5 ngg-1 and 15 ngg-1, respectively. The mean levels of the acrylamide contents in rice tah-dig, bread tah-dig, and potato tah-dig were measured as 24.65 ngg-1, 39.48 ngg-1, and 714.11 ngg-1, respectively. The highest acrylamide content was determined in potato tah-dig (2100 ngg-1) and the lowest acrylamide in rice tah-dig (≤LOQ). Based on the conducted risk assessment, the P (95%) of cumulative probability in the MCS method, the lowest and highest THQ was observed in the adults (ingestion bread tah-dig: 1.29E-2), and children (ingestion potato tah-dig: 1.90E+00), respectively. Additionally, the lowest and highest ILCR were reported in adults (ingestion bread tah-dig: 1.29E-5) and children (ingestion potato tah-dig: 7.49E-3), respectively. The rank order of type tah-dig based on THQ and ILCR for all groups of consumers was potato tah-dig > rice tah-dig > bread tah-dig. There is a considerable non-carcinogenic risk for the children due to ingestion potato tah-dig (THQ > 1). Additionally, the significant carcinogenic risk for the Iranian adults and children due to consumption of rice, bread, and potato tah-dig (ILCR > 1.00E-5) was observed.