Therapy with regulatory T-cell infusion in autoimmune diseases and organ transplantation: A review of the strengths and limitations.

In the last decade, cell therapies have revolutionized the treatment of some diseases, earning the definition of being the "third pillar" of therapeutics. In particular, the infusion of regulatory T cells (Tregs) is explored for the prevention and control of autoimmune reactions and acute/chronic allograft rejection. Such an approach represents a promising new treatment for autoimmune diseases to recover an immunotolerance against autoantigens, and to prevent an immune response to alloantigens. The efficacy of the in vitro expanded polyclonal and antigen-specific Treg infusion in the treatment of a large number of autoimmune diseases has been extensively demonstrated in mouse models. Similarly, experimental work documented the efficacy of Treg infusions to prevent acute and chronic allograft rejections. The Treg therapy has shown encouraging results in the control of type 1 diabetes (T1D) as well as Crohn's disease, systemic lupus erythematosus, autoimmune hepatitis and delaying graft rejection in clinical trials. However, the best method for Treg expansion and the advantages and pitfalls with the different types of Tregs are not fully understood in terms of how these therapeutic treatments can be applied in the clinical setting. This review provides an up-to-date overview of Treg infusion-based treatments in autoimmune diseases and allograft transplantation, the current technical challenges, and the highlights and disadvantages of this therapeutic approaches."

Impaired CD4+ Cytotoxic T Lymphocyte Activity in Polyomavirus BK Infected Kidney Transplant Recipients.

The reactivation of polyomavirus BK (BKPyV) contributes to increased morbidity and mortality rates of transplant patients, especially kidney transplant recipients (KTRs). CD4+ T cells are important immune cells active during BKPyV infection in KTRs. This research tried to examine the phenotype of CD4+ T cells in the stage of BKPyV activation in KTRs.The re cipients were separated into 2 groups of BKPyV-active and nonactive KTRs (10 patients in each group) and were compared with 10 healthy control subjects. The viral load was evaluated by Taq-man quantitative real-time PCR. The frequency of different CD4+ T cell subsets was determined by analyzing markers such as CD45RO, CCR7, CD27, CD107a, perforin, and granzyme B using flow cytometry. The gene expression levels of transcription factors, including TBX21, GATA3, STAT3, and STAT6, contributing to CD4+ T cell activation, were also assessed. A significantly higher proportion in CCR7+CD27+CD45RO-CD4+ T cell (naive Tcell) subsets was detected in BKPyV-active KTRs compared to nonactive ones. A significant increase was detected in the frequency of CD107a+, perforin+, and granzyme B+ CD4+ T cells in the BKPyV-active group compared to the nonactive group. In CD4+ T cells of KTRs, the mRNA expression of TBX21  and GATA3 was significantly increased in KTRs without BKPyV reactivation compared to BKPyV-active ones. This investigation focused on the CD4+ T cell as an immunodominant T cell type with potential cytotoxicity. Based on these results, BKPyV may have a direct influence on the repertoire of CD4+ T cell subsets. Particularly, cytotoxic CD4+ T cells need further investigation to be considered as a therapeutic approach for BKPyV infection.

Immune checkpoint molecules in prevention and development of asthma.

Allergic asthma is a respiratory disease initiated by type-2 immune responses characterized by secretion of alarmins, interleukin-4 (IL-4), IL-5, and IL-13, eosinophilic inflammation, and airway hyperresponsiveness (AHR). Immune checkpoints (ICPs) are inhibitory or stimulatory molecules expressed on different immune cells, tumor cells, or other cell types that regulate immune system activation and maintain immune homeostasis. Compelling evidence indicates a key role for ICPs in both the progression and prevention of asthma. There is also evidence of asthma development or exacerbation in some cancer patients receiving ICP therapy. The aim of this review is to provide an updated overview of ICPs and their roles in asthma pathogenesis, and to assess their implications as therapeutic targets in asthma.

The Impact of HLA-G and HLA-E Polymorphisms on CMV Reinfection in Liver Transplant Recipients.

BACKGROUND: Cytomegalovirus (CMV) reinfection in transplant patients has been associated with graft loss and decreased patient survival. In this regard, the HLA-G molecule has the immunomodulatory characteristic and its soluble isoforms have important roles in immunity to viruses. The 14bp insertion/deletion polymorphism impacts HLA-G mRNA stability. Regarding the HLA-E molecule, two nonsynonymous alleles, HLA-E*0101, and HLA-E*0103 are different in their functions including the affinity of the relative peptide. OBJECTIVE: To explore the possible link between HLA-G and HLA-E polymorphisms with CMV reinfection among liver transplant recipients (LTRs). METHODS: In this study, a total of 140 liver transplantations were performed; of which 70 CMV-reactivated LTRs and 70 CMV non-reactivated ones were recruited. The cut-off value of CMV DNA was determined to be 100 copies/mL. PCR evaluated different genotypes for HLA-G and ARMS-PCR for HLA-E*0101 and *0103. RESULTS: Neither the HLA-G genotypes (-14 bp/-14bp and +14bp/+14 bp homozygous genotypes with the p-values: 0.43, and 0.13, respectively +14 bp/-14 bp heterozygous genotype with p-value: 0.49) nor the HLA-E genotypes (HLA-E*0101/0103, HLA-E*0101/0101, and HLA-E*0103/0103 with the p-values: 0.152, 0.249, and 0.391, respectively) had any association with CMV reinfection in the LTRs. CONCLUSION: No difference was observed in the HLA-E and HLA-G genotype frequencies between our studied groups. Further studies are needed to explore other genetic variations and evaluate soluble HLA-G and HLA-E levels in the transplant population.

Altered Signatures of Plasma Inflammatory Proteins and Phonotypic Markers of NK Cells in Kidney Transplant Patients upon CMV Reactivation.

Cytomegalovirus (CMV) reactivation remains a common opportunistic infection with a prominent role in immune reconstitution in organ transplant recipients. CMVs as important drivers of natural killer (NK) cell differentiation has been indicated to prompt several phenotypic and functional alteration in these cells. We aimed to monitor the reconstitution of NK cells and change the signature of inflammatory proteins at the critical phase of CMV reactivation over six months after kidney transplantation. The present study indicated that CMV reactivation is associated with the development of IL-6, IL-10, and cytotoxic granules, including granzyme-B and granulysin, and the drop in the frequency of CD16 + NKG2A-CD57 + NK cell subset in kidney transplant recipients (KTRs) with reactivation versus non- reactivated ones. Our findings describe distinct immune signatures that emerged with CMV reactivation after kidney transplantation, which may be helpful in the timely management of CMV infection in KTRs.

Immune Cell-Derived Extracellular Vesicles in the Face of Pathogenic Infections.

Extracellular Vesicles (EVs) are a collection of vesicles released from cells that play an important role in intercellular communication. Microbial infections are known as one of the major problems in the medical field. Considering the increasing resistance of strains to routine drug treatments, the need for new therapies seems to be more than ever. Recent studies have shown that the EVs released from immune cells during microbial infections had anti-microbial effects or were able to induce neighbouring cells to display anti-microbial effects. This mini-review aimed to explore the latest studies on immune cell-derived EVs in viral, bacterial, fungal, and parasitic infections. Review of the literature demonstrated that specific cargos in EVs were involved in the fight against pathogenic infections. Additionally, the transport of appropriate bioactive molecules including miRNAs, mRNAs, and proteins via EVs could mediate the anti-microbial process. Thus, it could be a proof-of-principle that therapeutic approaches based on EVs derived from immune cells could offer a promising path forward, which is still in early stages and needs further assessments.

An Update on Protective Effectiveness of Immune Responses After Recovery From COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits variable immunity responses among hosts based on symptom severity. Whether immunity in recovered individuals is effective for avoiding reinfection is poorly understood. Determination of immune memory status against SARS-CoV-2 helps identify reinfection risk and vaccine efficacy. Hence, after recovery from COVID-19, evaluation of protective effectiveness and durable immunity of prior disease could be significant. Recent reports described the dynamics of SARS-CoV-2 -specific humoral and cellular responses for more than six months in convalescent SARS-CoV-2 individuals. Given the current evidence, NK cell subpopulations, especially the memory-like NK cell subset, indicate a significant role in determining COVID-19 severity. Still, the information on the long-term NK cell immunity conferred by SARS-CoV-2 infection is scant. The evidence from vaccine clinical trials and observational studies indicates that hybrid natural/vaccine immunity to SARS-CoV-2 seems to be notably potent protection. We suggested the combination of plasma therapy from recovered donors and vaccination could be effective. This focused review aims to update the current information regarding immune correlates of COVID-19 recovery to understand better the probability of reinfection in COVID-19 infected cases that may serve as guides for ongoing vaccine strategy improvement.

Suggesting Tissue-Specific MSMB Gene Promoter as a Novel Approach for Prostate Targeted Gene Therapy.

BACKGROUND AND AIM: Prostate cancer is the second most common cancer among men that has affected their quality of life. This study aimed to find prostate tissue-specific genes using bioinformatics methods to specifically target prostate cells in case of metastasis to other tissues. MATERIALS AND METHODS: In this study, after finding a specific gene (MSMB)  that is highly expressed in cancer, the optimal promoter region of this gene was isolated and inserted in an expression vector. Then, this vector was transfected into two prostate cancer cell lines (DU145 and LNCaP) and three non-prostate cell lines  (LX-2, MRC-5, and U87) using the PEI chemical method. The expression of this vector in these cells was examined using fluorescent microscopy and flow cytometry. RESULTS: We observed that the expression of MSMB promoter in DU145 cell line has a much higher activity than the CMV promoter, which is a ubiquitous promoter. The MSMB promoter didn't show any activity in cells other than that of prostate derived cell lines. CONCLUSION: MSMB  gene promoter with specific expression and high efficiency in prostate tissue compared to CMV promoter can play an essential role in gene therapy of prostate cancer.

Loss of CCR7 Expression on CD57 + CD56/ CD16 + NK Cells Correlates with Viral Load in CMV Reactivated Kidney Transplant Recipients.

INTRODUCTION: Despite developing strategies for antiviral treatment, cytomegalovirus (CMV) infection remains one of the most common challenges in kidney transplant recipients (KTRs). The evaluation of CMV viral load is still the most practical main clinical approach for CMV assessment and guides decision-making in recipient antiviral treatment. However, there is not a specific viral load cut off for initiating treatment yet. On the other hand, the cellular immune system and the innate immune response prove their roles in diagnosing CMV reinfection and monitoring the therapeutic regime to control CMV. Interactions among the components of cellular immunity encounter CMV reactivation provide a strong treatment management plan for clinical decisions about antiviral therapy against CMV. Natural killer (NK) cells, as essential effector cells, present potentially antiviral activity through distinct subpopulations. CCR7expressing NK cells were identified by high cytotoxicity and functionality among NK cell subsets. Here, we explored the correlation between CCR7+ expressing NK cells with viral load in CMV reactivated-kidney transplant recipients. MATERIALS AND METHODS: A cross-sectional study was conducted among ten CMV reactivated KTRs. The CMV DNA copy number was evaluated utilizing real-time PCR.NK cell phenotypic profiling was done using flow cytometry. RESULTS: Increasing of CMV viral load in CMV reactivated KTRs had a negative correlation with CCR7+CD57+ CD56/CD16+ NK cell (P < .05 r = -0.7) after CMV reactivation. Significantly increased level of CCR7-CD57- CD56/CD16+ NK cell was associated with CMV viral load within CMV reactivated KTRs (P < .05, r = 0.68). CONCLUSION: CCR7 expression is associated with CMV reactivation, which offers a new aspect of CMV-associated immunity within the NK cell compartment.  DOI: 10.52547/ijkd.6721.

Susceptibility to Metabolic Diseases in COVID-19: To be or Not to be an Issue.

Despite the passage of more than 17 months from the beginning of the COVID-19 pandemic, challenges regarding the disease and its related complications still continue in recovered patients. Thus, various studies are underway to assay the long-term effects of COVID-19. Some patients, especially those with severe symptoms, experience susceptibility to a range of diseases and substantial organ dysfunction after recovery. Although COVID-19 primarily affects the lungs, multiple reports exist on the effect of this infection on the kidneys, cardiovascular system, and gastrointestinal tract. Studies have also indicated the increased risk of severe COVID-19 in patients with diabetes. On the other hand, COVID-19 may predispose patients to diabetes, as the most common metabolic disease. Recent studies have shown that Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) binds to Angiotensin-Converting Enzyme 2 (ACE2) receptors, which are expressed in the tissues and organs involved in regulating the metabolic status including pancreas, adipose tissue, gastrointestinal tract, and kidneys. Therefore, SARS-CoV-2 may result in metabolic disturbance. However, there are still many unknowns about SARS-CoV-2, which are required to be explored in basic studies. In this context, special attention to molecular pathways is warranted for understanding the pathogenesis of the disease and achieving therapeutic opportunities. Hence, the present review aims to focus on the molecular mechanisms associated with the susceptibility to metabolic diseases amongst patients recovered from COVID-19.

The Direct Influence of Cytomegalovirus Lysate on the Natural Killer Cell Receptor Repertoire.

Natural killer (NK) cells are essential for controlling certain viral infections, including cytomegalovirus (CMV). In particular, the importance of NK cells in the context of CMV infection is underscored by the adaptive capabilities of these cells. Evidence suggests that some viruses can directly interfere with NK cell compartments and their activation and lead to shape-shifting the NK cell receptor repertoire. Still, it remains unknown whether the CMV can interact with NK cells without intermediaries. Here, we examined whether the direct effects of CMV lysate alter phenotypical properties of NK cells. To investigate this issue, NK cells were isolated from the blood of CMV seropositive healthy donors by negative magnetic separation. Isolated NK cells were cultured in the presence of CMV lysate and analyzed for the expression of NKG2A, NKG2C, and CD57 by FACS caliber. The results showed that NKG2C expression is significantly upregulated in the presence of CMV lysate compared to without stimulated group (mean increase, 6.65 %; 95% CI, 0.2582 to 13.02; p=0.043; R square: 0.38). Likewise, results have shown a significant decrease in the frequency of NKG2A+CD57- NK cell subsets (p=0.005; 95% CI, -13.49 to -3.151; R square: 0.5957) in the stimulated group compared to without stimulated ones. According to these results, CMV may drive a direct influence on NK cell receptor repertoire, including the expansion of NK cells expressing NKG2C receptor, which is needed for further studies.

Circulating NKG2C + NK cell expressing CD107a/LAMP-1 subsets at the onset of CMV reactivation in seropositive kidney transplant recipients.

Cytomegalovirus (CMV) infection contributes to morbidity and mortality among kidney transplant recipients. Natural killer (NK) cells can battle against CMV in kidney transplant recipients (KTRs). This study aimed to analyze the association between CMV reactivation and the proportion of NK cell subsets and their activity. In a cross-sectional study, ten CMV reactivated KTRs, and ten non- CMV reactivated ones were recruited. Ten matched healthy controls were also included in this cohort. The presence of anti-CMV-IgG Ab in both KTR subgroups from seronegative donors and healthy controls was determined. The frequency of distinct subsets of memory-like NK cells was analyzed through NKG2C, NKG2A, and CD57 using flow cytometry. The activity of NK cells was evaluated after stimulation via coculture with K562 cell line and then assessment of the frequency of CD107a and granzyme B. The mRNA levels of transcription factors, including T-bet, EAT, and inflammatory proteins, including IFN-γ and perforin contributing to NK cell activation, were also evaluated. Results showed a significantly lower frequency of NKG2C + NKG2A-CD57+ NK cell population in CMV-reactivated KTRs compared to non-reactivated ones (P-value:0.003). NKG2C+ NK cells expressing CD107a/LAMP-1 significantly was increased in CMV-reactivated KTRs compared to non-reactivated ones (P-value: 0.0002). The mRNA level of IFN-γ had a significant increase in the CMV-reactivated KTRs vs. nonreactive ones (P-value: 0.004). Finally, evaluation of the NK cells' cytotoxicity and activity through assessment of CD107a/LAMP-1 expression and IFN-γ secretion may be helpful for the identification of the risk of CMV reactivation in KTRs.

Stem Cell-Derived Exosome as Potential Therapeutics for Microbial Diseases.

Exosomes, as the smallest extracellular vesicles that carry a cargo of nucleic acids, lipids, and proteins and mediate intercellular communication, have attracted much attention in diagnosis and treatment in the field of medicine. The contents of exosomes vary depending on the cell type and physiological conditions. Among exosomes derived from several cell types, stem cell-derived exosomes (stem cell-Exo) are increasingly being explored due to their immunomodulatory properties, regenerative capacity, anti-inflammatory and anti-microbial functions. Administration of stem cell-Exo, as a cell-free therapy for various diseases, has gained great promise. Indeed, the advantages of exosomes secreted from stem cells outweigh those of their parent cells owing to their small size, high stability, less immunogenicity, no risk of tumorigenesis, and easier condition for storage. Recently, the use of stem cell-Exo has been proposed in the field of microbial diseases. Pathogens including bacteria, viruses, fungi, and parasites can cause various diseases in humans with acute and chronic complications, sometimes resulting in mortality. On the other hand, treatments based on antibiotics and other chemical compounds have many side effects and the strains become resistant to drugs in some cases. Hence, this review aimed to highlight the effect of stem cell-derived extracellular vesicles including stem cell-Exo on microbial diseases. Although most published studies are preclinical, the avenue of clinical application of stem cell-Exo is under way to reach clinical applications. The challenges ahead of this cell-free treatment that might be applied as a therapeutic alternative to stem cells for translation from bench to bed were emphasized, as well.

Harnessing Memory NK Cell to Protect Against COVID-19.

The worldwide struggle against the coronavirus disease 2019 (COVID-19) as a public health crisis continues to sweep across the globe. Up to now, effective antiviral treatment against COVID-19 is not available. Therefore, throughout virus infections, a thorough clarification of the virus-host immune system interactions will be most probably helpful to encounter these challenges. Emerging evidence suggests that just like SARS and MERS, COVID-19 primarily suppresses the innate immune system, enabling its stable propagation during the early stage of infection. Consequently, proinflammatory cytokines and chemokines have been increasing during infection progression associated with severe lung pathology. It is imperative to consider hyper inflammation in vaccine designing, as vaccine-induced immune responses must have a protective role against infection without leading to immunopathology. Among the front-line responders to viral infections, Natural Killer (NK) cells have immense therapeutic potential, forming a bridge between innate and adaptive responses. A subset of NK cells exhibits putatively increased effector functions against viruses following pathogen-specific and immunization. Memory NK cells have higher cytotoxicity and effector activity, compared with the conventional NK cells. As a pioneering strategy, prompt accumulation and long-term maintenance of these memory NK cells could be an efficacious viral treatment. According to the high prevalence of human cytomegalovirus (HCMV) infection in the world, it remains to be determined whether HCMV adaptive NK cells could play a protective role against this new emerging virus. In addition, the new adaptive-like KIR+NKG2C+ NK cell subset (the adaptive-like lung tissue residue [tr]NK cell) in the context of the respiratory infection at this site could specifically exhibit the expansion upon COVID-19. Another aspect of NK cells we should note, utilizing modified NK cells such as allogeneic off-the-shelf CAR-NK cells as a state-of-the-art strategy for the treatment of COVID-19. In this line, we speculate introducing NKG2C into chimeric antigen receptors in NK cells might be a potential approach in future viral immunotherapy for emerging viruses. In this contribution, we will briefly discuss the current status and future perspective of NK cells, which provide to successfully exploit NK cell-mediated antiviral activity that may offer important new tools in COVID-19 treatment.

Viral ecosystem: An epidemiological hypothesis.

Viruses are incomplete elements that require other organisms to survive and multiply, hence constantly mutate during its evolution, resulting from adaptations in response to environmental changes such as the immune response of the host. In this line, they are responsible for many diseases, but today, there is evidence that viruses have many benefits and even have a unique ecosystem to control the different species or strain of themselves. While highlighting the benefits of some viruses and the undesirable effects of their eradication, the present review expresses the idea of the viral ecosystem and its importance, which has been supported in several studies. There are countless articles about virus-related illnesses and the undesirable effects of therapeutic interventions in eliminating the less pathogenic viruses or manipulating viral ecosystems. By simulating the viral ecosystem with an ecosystem found among the snakes, it can be assumed that the viruses have concentric zones, which its inner zone includes the most dangerous viruses for humans and each zone is surrounded and controlled by an outer zone of less dangerous viruses for humans. The outermost zone consists of viruses that are least dangerous to humans such as common cold that protect humans and possibly other living organisms against more dangerous viruses in inner zone, causing the activation of immune system by playing a unique and pivotal role in the ecosystems. Therefore, manipulating the ecosystem and disrupting the balance might have epidemics and harmful consequences for the plants, animals, and human.

Ethical considerations in sex selection.

Advances in modern medicine are resulted from unrestricted and unlimited research disregarding many essentials of a research including ethical issues. Following ethical issues, many of unwanted pregnancies and abortions can be avoided. Several factors such as medical issues including X linked disease, has encouraged couples to select traditional or modern techniques in selecting the gender of their children. Some of these methods are corrected Swim-up method or washing of spermatozoa, Percoll gradient sperm separation method, grass wool column filter method method, albumin separation method, microsort method using FISH (Fluorescence in situ hybridization), free electrophoresis method, Ph adjustment method, pre implantation genetic diagnosis (PGD)/fluorescence in situ hybridization. This technology is confronted with many ethical issues. Ethical considerations PGD in the SEX SELECTION differ in different religions and their perspectives on this issue. In this this review, electronic databases, books and Internet sites were completely searched and full articles including required keywords and techniques were obtained and reviewed. The rites and religions, were different and had legal perspectives and opinions about PGD. In some non-Islamic countries there are strict rules to control the use of technology. Some of these methods are costly and even risky. They also involve ethical issues such as legitimacy of the conceived fetus; recommending final touches in sex selection is still considered a taboo and a big issue in some cultures or mono-sexual families. Islamic views and beliefs are more flexible and the use of these technologies are allowed to preserve the health and lives permit. Islam strongly favors humanity and supports different issues if they are not in conflict with the primary concept of legitimate reproduction and are beneficial to human beings.

Multiplex PCR Screening of Y-chromosome microdeletions in azoospermic ICSI candidate men.

BACKGROUND: It has been hypothesized that Y-q microdeletion can account for significant proportion of infertility in men. There are three nonoverlapping regions referred to as the "azoozpermia factors" AZFa, AZFb, and AZFc from proximal to distal part of Y-q. These have been defined as spermatogenesis loci, this region deletions have been shown to be involved in male azoospermic or severe oligoozospermic infertility. OBJECTIVE: Evaluation the rate of Y-chromosome microdeletions in infertile men. MATERIALS AND METHODS: In this case-control study, 25 azoospermic infertile men candidate for intracytoplasmic sperm injection (ICSI) were selected as case group. For control group, 25 normoozoospemric men were selected. All cases and controls had normal 46XY karyotype. DNA extraction and molecular analysis were done on blood samples. Multiplex-PCR method was done to identify the presence of microdeletion in AZFa, AZFb or AZFc loci. Eight STS primers that include two controls were selected to determine Y-chromosome microdeletions. RESULTS: 20% (5/25) of all patients have at least one microdeletion in more than one region of AZF loci. Totally 17 microdeletions was observed, one case had deletions in three AZF regions, and 4 cases had deletions in two AZF regions. The rate of deletions was 42% (7/17) for AZFc, 35% (6/17) for AZFa and 23% (4/17) for AZFb. CONCLUSION: The molecular DNA analysis could help us to know the real cause of infertility and can give good information for good decision for example in men whit microdeletions who want to undertake ICSI procedure the deletions will be passed to their son.

Association between Y-chromosome AZFc region micro-deletions with recurrent miscarriage.

BACKGROUND: In human, about 25% of implanted embryos are losing 1-2 week following attachment to the uterus. A subset of this population will have three or more consecutive miscarriages which define as repeated pregnancy loss (RPL). Introducing the assisted reproductive technologies (ARTS) made a chance for infertile couples to solve their childless problem. OBJECTIVE: This study was conducted to evaluate the incidence of Y-chromosome AZF region's micro-deletions in male partners of couples with recurrent miscarriage (RM). MATERIALS AND METHODS: Thirty male partner of couples with RM and thirty infertile males, who referred to the Yazd Research and Clinical Center for Infertility were recruited to this study. In addition, 30 healthy men were screened as a control group from the same center. After DNA extraction using salting out method, the multiplex-PCR was done for amplifying 8 known STSs proximal to the AZF region of the Y-chromosome. The results were compared between the groups using Fisher's exact t-test and p<0.05 was considered statistically significant. RESULTS: Of the 30 infertile males, 5 (16.6%) cases were associated with the AZF region micro-deletions of DYF87S, DYF84S1, DYF83S1 and DYF51S1, STSs. But in the fertile and RM male groups was found no deletions similar to those, of the infertile males (p=1.0). Instead 4 (13.3%) cases of the RM group males had different micro-deletions included DYS220 (AZFb, sY129), DYS262, DYF8551, and DYF8651, STSs. The AZFc locus of Y-chromosome micro-deletions have a significant role in RM (p=0.045). CONCLUSION: It seems that the Y-chromosome AZF region's micro-deletions are associated with RM, and we recommend adding this AZF region STSs into infertility analyzing panels.