This research attempted to elucidate the molecular components are involved in the pathogenesis of recurrent implantation failure (RIF). We initially identified that 386 mRNAs, 144 miRNAs and 2548 circRNAs were differentially expressed (DE) in RIF and then investigated the genetic cause of the observed abnormal expression by constructing a circRNA‐miRNA‐mRNA network considering the competing endogenous RNA theory. We further analysed the upstream transcription factors and related kinases of DEmRNAs (DEMs) and demonstrated that SUZ12, AR, TP63, NANOG, and TCF3 were the top five TFs binding to these DEMs. Besides, protein‐protein interaction analysis disclosed that ACTB, CXCL10, PTGS2, CXCL12, GNG4, AGT, CXCL11, SST, PENK, and FOXM1 were the top 10 hub genes in the acquired network. Finally, we performed the functional enrichment analysis and found that arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), pathways in cancer, TNF signalling pathway and steroid hormone biosynthesis were the potentially disrupted pathways in RIF patients. Optimistically, our findings may deepen our apprehensions about the underlying molecular and biological causes of RIF and provide vital clues for future laboratory and clinical experiments that will ultimately bring a better outcome for patients with RIF.

Background. Male infertility is a main clinical problem that affects about 7% of all men worldwide. Many patients with male infertility are caused by a reduced antioxidant capacity of semen. Several antioxidant supplements, especially vitamin E, are proposed to help male infertility treatment. This project was goaled to study the effects of oral synthetic vitamin E (400 IU/day) for eight weeks on betterment of semen parameters and pregnancy rate. Methods. After dropping the cases, 124 infertile couples with a male factor who were admitted to the IVF program were included. The male patients with idiopathic abnormal motility and/or morphology were randomized into two groups: 61 receiving vitamin E and 63 as the control group receiving placebo for eight weeks. The pretreatment semen parameters of both groups were compared with those of posttreatment. The pregnancy outcomes were considered between the two groups. Results. There were no significant differences statistically between before and after treatment in the term of sperm volume, count, motility, and morphology. Furthermore, the IVF outcomes of the two groups were not different significantly, either. Interestingly, the percent of normal sperm in the placebo group was significantly decreased after eight weeks. Conclusion. Vitamin E supplementation might neutralize free radical activity to keep sperm from more oxidative damages. Further studies regarding the influence of higher acceptable doses of vitamin E on semen characteristics and fertility rates are needed. This study was registered as a two‐arm, blinded, randomized, placebo‐controlled clinical trial (IRCTID: IRCT2014020616506N1, 2014‐03‐18).

Coronavirus disease 2019 (COVID-19), a global pandemic, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2 and transmembrane serine protease 2 (TMPRSS2) facilitates ACE2-mediated virus entry. Moreover, the expression of ACE2 in the testes of infertile men is higher than normal, which indicates that infertile men may be susceptible to be infected and SARS-CoV-2 may cause reproductive disorder through the pathway induced by ACE2 and TMPRSS2. Little is known about the pathway regulation of ACE2 and TMPRSS2 expression in male reproductive disorder. Since the regulation of gene expression is mediated by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) at the post-transcriptional level, the aim of this study was to analyze the dysregulated miRNA–lncRNA interactions of ACE2 and TMPRSS2 in male reproductive disorder. Using bioinformatics analysis, we speculate that the predicted miRNAs including miR-125a-5p, miR-125b-5p, miR-574-5p, and miR-936 as regulators of ACE2 and miR-204-5p as a modulator of TMPRSS2 are associated with male infertility. The lncRNAs with a tissue-specific expression for testis including GRM7-AS3, ARHGAP26-AS1, BSN-AS1, KRBOX1-AS1, CACNA1C-IT3, AC012361.1, FGF14-IT1, AC012494.1, and GS1-24F4.2 were predicted. The identified miRNAs and lncRNAs are proposed as potential biomarkers to study the possible association between COVID-19 and male infertility. This study encourages further studies of miRNA–lncRNA interactions to explain the molecular mechanisms of male infertility in COVID-19 patients.

Non-obstructive azoospermia is a severe infertility factor. Currently, the etiology of this condition remains elusive with several possible molecular pathway disruptions identified in the post-meiotic spermatozoa. In the presented study, in order to identify all possible candidate genes associated with azoospermia and to map their relationship, we present the first protein-protein interaction network related to azoospermia and analyze the complex effects of the related genes systematically. Using Online Mendelian Inheritance in Man, the Human Protein Reference Database and Cytoscape, we created a novel network consisting of 209 protein nodes and 737 interactions. Mathematical analysis identified three proteins, ar, dazap2, and esr1, as hub nodes and a bottleneck protein within the network. We also identified new candidate genes, CREBBP and BCAR1, which may play a role in azoospermia. The gene ontology analysis suggests a genetic link between azoospermia and liver disease. The KEGG analysis also showed 45 statistically important pathways with 31 proteins associated with colorectal, pancreatic, chronic myeloid leukemia and prostate cancer. Two new genes and associated diseases are promising for further experimental validation.

The development of new computational approaches that are able to design the correct personalized drugs is the crucial therapeutic issue in cancer research. However, tumor heterogeneity is the main obstacle to developing patient-specific single drugs or combinations of drugs that already exist in clinics. In this study, we developed a computational approach that integrates copy number alteration, gene expression, and a protein interaction network of 73 basal breast cancer samples. 2509 prognostic genes harboring a copy number alteration were identified using survival analysis, and a protein–protein interaction network considering the direct interactions was created. Each patient was described by a specific combination of seven altered hub proteins that fully characterize the 73 basal breast cancer patients. We suggested the optimal combination therapy for each patient considering drug–protein interactions. Our approach is able to confirm well-known cancer related genes and suggest novel potential drug target genes. In conclusion, we presented a new computational approach in breast cancer to deal with the intra-tumor heterogeneity towards personalized cancer therapy.

Background: Insulin resistance (IR) occurs in 50–70% of women with polycystic ovary syndrome (PCOS) and can be applied as a prediabetic feature in PCOS. Objective: In this study, indirect methods including fasting blood sugar (FBS), fasting insulin (FI), FBS/FI ratio, and quantitative insulin sensitivity check index (QUICKI) were compared with the homeostasis model assessment of insulin resistance (HOMA-IR) as a standard technique. The association of IR to sex hormone-binding globulin (SHBG) and several hormones was also analyzed. Materials and Methods: This cross-sectional study was performed on 74 PCOS women. Sensitivity and specificity of each IR method was calculated based on HOMA-IR. Hormonal profiles of the patients were compared between the groups with defined normal and abnormal values of IR. Results: Triglyceride levels had a positive association with FBS and HOMA-IR (p = 0.002 and p = 0.01, respectively) with a negative association to QUICKI and SHBG (p = 0.02 and p = 0.02, respectively). SHBG showed a significant negative association with FBS (p = 0.001). Dehydroepiandrosterone sulfate showed a positive association with FI (p = 0.002). Seven PCOS women showed abnormal SHBG levels (< 36 nmol/L) while expressed normal values of the rest of the studied variables. FI and QUICKI had the highest sensitivity while FBS/FI and QUICKI had the highest specificity when HOMA-IR was applied as a standard test. Conclusion: SHBG and triglyceride had a significant negative and positive association with IR, respectively. HOMA-IR followed by FI and QUICKI is the most sensitive test for the detection of IR. SHBG levels can be a helpful biomarker for the diagnosis of PCOS. Key words: Polycystic ovary syndrome, Insulin resistance, Sex hormone-binding globulin.