Endometrial gene expression profiling of recurrent implantation failure after in vitro fertilization.

Recurrent implantation failure (RIF) is diagnosed when good-quality embryos repeatedly fail to implant after transfer in several in vitro fertilization (IVF) treatment cycles. Different expression profiles in maternal mRNAs could be referring to many diseases including RIF. This study aimed to reveal significantly dysregulated selected genes expression between healthy fertile women and RIF patients in the implantation window days of the natural menstrual cycle. MME, WWC1, TNC, and FOXP3 genes were chosen as target genes regarding their possible relations with the implantation process. Pathways with these genes were identified and the relationship between these pathways and RIF was investigated. In this study, the endometrial biopsy samples were collected in the secretory phase (cycle day 20-24) of the menstrual cycle from RIF patients (n = 34) and healthy fertile controls (n = 34). After "Pathway and network-oriented GWAS analysis" (PANOGA) and "Kyoto Encyclopedia of Genes and Genomes" (KEGG) pathway analysis; "Membrane Metalloendopeptidase" (MME), "WW and C2 Domain Containing 1" (WWC1), "Tenascin C" (TNC) and "Forkhead Box P3" (FOXP3) genes were chosen as target genes by regarding their possible relation with implantation process. Detection of differences in mRNA expressions between the control group and RIF patients has been performed with the droplet digital PCR (ddPCR) method. Results of the study showed that MME and WWC1 genes expression levels are significantly (p < 0,05) up-regulated 4.9 and 5.2 times respectively and TNC gene expression level is significantly (p < 0,05) down-regulated 9 times in the RIF samples compared to the control group. However, no statistically significant difference was observed between the patient group and the control group in the expression of the FOXP3 gene (p < 0.05). Changes are observed in the expression of the renin-angiotensin system pathway in which the MME gene is involved in the implantation process. The increase in MME gene expression can be speculated to cause implantation failure by restricting the invasion of trophoblast cells. Increasing WWC1 gene expression in the Hippo signaling pathway inhibits "Yes-associated protein 1" (YAP) expression, which is a transcriptional cofactor. Inhibition of YAP protein expression may impair the implantation process by causing the failure of endometrial decidualization. The TNC gene is located in the focal adhesion pathway and this pathway reduces cell adhesion on the endometrial surface to facilitate the attachment of the embryo to the endometrium. The reason for implantation failure might be that the intercellular connections are not suitable for implantation as a result of decreased expression of the focal adhesion pathway in which the TNC gene is effective. Considering the relations between the pathways of the target genes and the implantation process, changes in the expression of target genes might be a cause of RIF.

Prevalence of class 1 integron among multidrug-resistant Acinetobacter baumannii in Tabriz, northwest of Iran.

Integrons are associated with a variety of gene cassettes, which confer resistance to multiple classes of antibacterial drugs. In this study we tested the frequency of class 1 and 2 integrons among multidrug-resistant Acinetobacter baumannii (MDRAB) clinical isolates. One hundred clinical isolates of A. baumannii were screened for carriage of class 1 and 2 integrons by PCR method. Results showed that seventy four (92.5%) of 80 MDRAB carried class 1 integron. Integron-positive isolates were statistically more resistant to aminoglycoside, quinolone and beta-lactam compounds except for cefepime. This is the first report of class 1 integrons in MDRAB isolates in northwest Iran.

The role of the serum exosomal and endometrial microRNAs in recurrent implantation failure.

OBJECTIVE: It has been identified that endometrium specific microRNAs have different expression levels in endometrial tissues and maternal serum during endometrial cycle. The aim of this study was to analyze microRNA expression levels in recurrent implantation failure patients and healthy controls endometrial samples for enlightening the aetiopathogenesis of the disease. The second aim was to search for a potential noninvasive molecular biomarker in early diagnosis and treatment of Recurrent Implantation Failure (RIF) patients. METHODS: Endometrium and serum samples in two different phases (PP; proliferative phase and SP; secretory phase) from the same cases (RIF; n = 12 and Control; n = 8) were obtained. The expression levels of the microRNA by RT-qPCR method were measured. The expression levels of the healthy controls and study group were compared. Lastly performed target genes analysis of significantly dysregulated miRNA by target analyze databases for obtained related biological pathways. RESULTS: This study showed that has-miR-145, has-miR-23b, has-miR-31 and has-miR-30b were significantly up-regulated in PP and down-regulated in SP endometrium samples. In serum samples, has-miR-145 and hsa-miR-23b were significantly down-regulated in both of PP and SP. Target gene and pathway analysis for dysregulated miRNAs identified important, validated and predicted genes for the implantation process. CONCLUSIONS: This study is the first study to obtain endometrium and serum samples in two different phases from the same cases and measure the candidate miRNAs expression. Our finding suggests that expression level of four candidate miRNAs may be involved in RIF development in women. Furthermore, these miRNAs can be potential biomarker for early diagnosis of RIF patients.

Prevalence of PER and VEB Type Extended Spectrum Betalactamases among Multidrug Resistant Acinetobacter baumannii Isolates in North-West of Iran.

OBJECTIVE(S): Drug resistant Acinetobacter baumannii have emerged as a major problem in many hospitals and intensive care units. Various types of extended spectrum beta-lactamases (ESBLs) are responsible for resistance to beta-lactam antibiotics in different parts of the world. The objective of this study was to determine the prevalence of integron class1 (INT 1) and ESBL types PER-1, PER-2 and VEB-1 among A. baumannii strains isolated from Tabriz, North-West of Iran. MATERIAL AND METHODS: A total of 100 A. baumannii isolates collected from different clinical samples were included in the study. Antimicrobial susceptibility profiles were determined using the Kirby Bauer disk diffusion method. Production of ESBL was investigated by testing resistance against ceftazidime, cefotaxime, ceftriaxone and verified by Double Disk Synergy Test. DNA was extracted from the isolates and the frequency of INT 1 and ESBL types PER-1, PER-2 and VEB-1 were determined by PCR using specific primers. RESULTS: Among 100 A. baumannii isolates screened, 80 isolates were multidrug-resistant and 70 isolates were positive for ESBL production. PCR screening revealed that 74 % of the isolates contained class 1 integron, 51% were positive for PER-1 gene, 10% positive for VEB1 whereas none of the isolates were positive for PER2 type gene. CONCLUSION: This is the first report of ESBL types VEB and PER in A. baumannii from North West of Iran. The results of this study demonstrated high prevalence of PER-1 and VEB-1 type ESBLs among A. baumannii isolates in the study region and reminded the necessity of appropriate infection control strategy to prevent further spread of infection by these organisms.