Autophagy genes and signaling pathways in endometrial decidualization and pregnancy complications.

Autophagy is a process that occurs in almost all eukaryotic cells and this process is controlled by several molecular processes. Its biological roles include the provision of energy, the maintenance of cell homeostasis, and the promotion of aberrant cell death. The importance of autophagy in pregnancy is gradually becoming recognized. In literature, it has been indicated that autophagy has three different effects on the onset and maintenance of pregnancy: embryo (embryonic development), feto-maternal immune crosstalk, and maternal (decidualization). In humans, proper decidualization is a major predictor of pregnancy accomplishment and it can be influenced by different factors. This review highlights the genes, pathways, regulation, and function of autophagy in endometrial decidualization and other involved factors in this process.

The role of neutrophils and neutrophil extracellular traps (NETs) in stages, outcomes and pregnancy complications.

Neutrophils are the main components of innate immunity to eliminate infectious pathogens. Neutrophils play a role in several stages of the reproductive cycle, and their presence in the female reproductive system is highly regulated, so their function may change during pregnancy. Emerging evidence suggests that neutrophils are important at all stages of pregnancy, from implantation, placentation, and connective tissue regeneration to birth, as well as birth itself. Neutrophil extracellular traps (NETs) are defined as extracellular strands of unfolded DNA together with histone complexes and neutrophil granule proteins. NET formation is a new mechanism of these cells for their defense function. These strands containing DNA and antimicrobial peptides were initially recognized as one of the defense mechanisms of neutrophils, but later it was explained that they are involved in a variety of non-infectious diseases. Since the source of inflammation and tissue damage is the irregular activity of neutrophils, it is not surprising that NETosis are associated with a number of inflammatory conditions and diseases. The overexpression of NET components or non-principled NET clearance is associated with the risk of production and activation of autoantibodies, which results in participation in autoinflammatory and autoimmune disorders (SLE, RA), fibrosis, sepsis and other disorders such as vascular diseases, for example, thrombosis and atherosclerosis. Recent published articles have shown the role of neutrophils and extracellular traps (NETs) in pregnancy, childbirth and pregnancy-related diseases. The aim of this study was to identify and investigate the role of neutrophils and neutrophil extracellular traps (NETs) in the stages of pregnancy, as well as the complications caused by these cells.

The effect of lymphocyte immunotherapy (LIT) in modulating immune responses in patients with recurrent pregnancy loss (RPL).

In order to prevent miscarriage in RPL patients, the goal of this study was to determine how well lymphocyte immunotherapy (LIT) works in modifying immunological responses produced by cells, cytokines, transcription factors, and microRNAs. 200 RPL patients and 200 healthy controls were included in the study. Using flow cytometry, it was possible to compare the frequency of cells before and after lymphocyte treatment. Real-time PCR was used to assess the gene expression levels of transcription factors, cytokines, and microRNAs. ELISA method was used to evaluate the level of secretion of cytokines in the serum. Primary evaluation of the immune profile between healthy controls and RPL cases showed a higher frequency of Th17, NK, B cells and a lower frequency of Treg cells in RPL cases. Also, pro-inflammatory cytokines showed increased expression at mRNA and protein levels in the RPL group in comparison with the control group. Whereas, anti-inflammatory cytokines showed decreased expression in RPL patients. Decreased and increased frequency of Th17 and Treg lymphocytes observed in RPL cases following LIT, respectively. The same results obtained for RORγt and FoxP3 mRNA expression as transcription factor of Th17 and Treg cells, respectively. NK cell cytotoxicity decreased after LIT in RPL patients. miR-326a and miR-155 expression after LIT reduced, but miR-146a and miR-10a expression increased in RPL instances. LIT in RPL cases causes to elevation and modulation of anti-inflammatory and pro-inflammatory cytokines. Our data showed that lymphocyte therapy can be proposed as an effective therapeutic agent in RPL patients with immunological background by a modulating inflammatory condition.

Dominant immune cells in pregnancy and pregnancy complications: T helper cells (TH1/TH2, TH17/Treg cells), NK cells, MDSCs, and the immune checkpoints.

Pregnancy problems including recurrent pregnancy loss, repeated implantation failure and pre-eclampsia  are common problems in the reproductive ages. Different reasons such as genetic, immunological, and environmental agents and also infections could develop these complications. In those cases in which the cause of the abortion is diagnosed, the chance of a successful pregnancy is increased by eliminating defective factors. However, in patients with unknown causes, there may be an imbalance in immune cells pattern. As a matter of fact, an inappropriate immune response is often associated with a failed pregnancy. Hence, the focus of treatment is to increase tolerance, not to suppress maternal immune system. These findings are linked to an elevated number of Treg cells and immune checkpoints through normal pregnancy. The present review discusses the balance of myeloid-derived suppressor cells, natural killer cells, T cells, and immune checkpoints, and also targeting them to maintain pregnancy and prevent associated complications.

Understanding main pregnancy complications through animal models.

Since human pregnancy is an inefficient process, achieving desired and pleasant outcome of pregnancy - the birth of a healthy and fit baby - is the main goal in any pregnancy. Spontaneous pregnancy failure is actually the most common complication of pregnancy and Most of these pregnancy losses are not known. Animal models have been utilized widely to investigate the system of natural biological adaptation to pregnancy along with increasing our comprehension of the most important hereditary and non-hereditary factors that contribute to pregnancy disorders. We use model organisms because their complexity better reproduces the human condition. A useful animal model for the disease should be pathologically similar to the disease conditions in humans. Animal models deserve a place in research because of the ethical limitations that apply to pregnant women's experiments. The present review provides insights into the overall risk factors involved in recurrent miscarriage, recurrent implant failure and preeclampsia and animal models developed to help researchers identify the source of miscarriage and the best research and treatment strategy for women with Repeated miscarriage and implant failure.

Investigation of Fc Receptor-Like 3 (FCRL-3) Gene Polymorphism (rs7528684) with Susceptibility to Allergic Asthma in Iranian North-Western Azeri Population.

BACKGROUND: Asthma is a clinical setting in which multiple cellular and molecular mechanisms are involved. Additionally, increasing genetic studies have provided evidence that single nucleotide polymorphisms (SNPs) in asthma relevant genes confer susceptibility to the disease. Fc receptor-like (FCRL) 3, a transmembrane molecule basically involved in B-cell signaling, mediates immune-disorders including allergy. Aim of study was to investigate the possible association of rs7528684 SNP in FCRL3 gene with a predisposition to allergic asthma in Iranian North-western Azeri population. METHODS: The frequency of genotypes and alleles of rs7528684 SNP in the FCRL3 gene was determined using the TaqMan genotyping method in 191 asthmatic patients and 186 healthy controls. RESULTS: The most frequent genotype in patients and control groups were CT (n = 81, 42.4%) and TT (n = 76, 40.9%), respectively. Statistical analysis showed no significant difference in genotype frequency (p = 0.81) and also in frequency of C and T alleles (p = 0.52) between two groups. CONCLUSIONS: Our results revealed no association between the rs7528684 SNP with susceptibility to allergic asthma in the included population. More studies in different ethnic groups will result in more valid conclusions.