Unlocking the Uterine Code: Microbiota, Immune Cells, and Therapy for Recurrent Reproductive Failure.

The uterine microbiota has been the subject of increasing study, but its interaction with the local immune system remains unclear. Successful embryo implantation relies on endometrial receptivity, which is pivotal for immunological tolerance to fetal antigens and precise regulation of inflammatory mediators. Emerging data suggest a dynamic interplay between endometrial microflora and the immune system, making dysbiosis a potential determinant of pregnancy outcomes. Imbalances in the regulation of immune cells in the endometrium and decidua have been associated with infertility, miscarriage, and obstetric complications. A thorough comprehension of the immune system in the female reproductive tract shows potential for improving women's health and pregnancy outcomes. The objective of this study was to evaluate the patterns of endometrial microbiota in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) and to explore their implications for endometrial immune cells and chronic endometritis (CE). Immune cells in biopsies from 107 RIF and 93 RPL patients were examined using flow cytometry. The endometrial microbial composition was analyzed using real-time polymerase chain reaction (RT-PCR). The research uncovered disrupted endometrial microbiota in most women with RIF and RPL, which was often associated with significant effects on lymphocytes, T cells, and uNK cells.

Anti-fibrillin-1 autoantibodies in normal pregnancy and recurrent pregnancy loss.

PROBLEM: The aim of this study was to investigate anti-fibrillin-1 autoantibody in patients with a history of recurrent pregnancy loss (RPL) and during normal pregnancy. METHOD OF STUDY: Anti-fibrillin-1 IgG and IgM antibodies were measured by a home made ELISA in serum samples of 48 medically and obstetrically normal pregnant women, classified to three trimester groups, 15 female patients with RPL and 26 healthy non-pregnant women classified to two control subgroups: (a) women who had already had at least one previous successful pregnancy and (b) women who had never been pregnant. Differences in anti-fibrillin-1 autoantibodies between the groups were analyzed for statistical significance (P<0.05) with one-way analysis of variance (ANOVA) and multiple comparison test - Post Hoc test, Least Significant Difference method. RESULTS: Anti-fibrillin-1 IgM autoantibodies were significantly decreased in the second and third trimester pregnant women compared to the nulligravida controls. RPL patients had significantly increased anti-fibrillin-1 IgM antibody compared to control group (a). CONCLUSION: Fibrillin-1 degradation seems to be decreased during the second and third trimester of normal pregnancy. Increased anti-fibrillin-1 IgM antibodies in RPL patients may be a secondary phenomenon of increased fibrillin-1 degradation and contribute to the pathogenesis of pregnancy losses.

Levels of platelet-leukocyte aggregates in women with both thrombophilia and recurrent pregnancy loss.

The aim of our study was to investigate the significance of platelet-leukocyte aggregates (PLA) in women with recurrent pregnancy loss (RPL) as well as to identify association between common thrombophilic factors and whole blood levels of PLA in these patients. We measured PLA by whole blood flow cytometry in 66 nonpregnant women with hereditary and/or acquired thrombophilia and RPL, classified to 3 study groups, according to the type of losses (first, second, and third trimester) and 35 age-matched healthy controls. Platelet-leukocyte aggregates levels in all study groups were significantly increased compared to the control group (median values 2.13%, 2.32%, and 2.41%, vs median value in the control group 1.39%, P < .05 for all comparisons). Women with a single thrombophilic factor and women with combination of thrombophilic factors did not differ significantly as regards the PLA levels (2.13% vs 2.27%, P = .4). This study suggests that PLA may have a role in the pathogenesis of RPL in women affected by hereditary or acquired thrombophilia.

Clinical case of acute myeloblastic leukemia with t(8;21)(q22;q22) in a patient with Klinefelter's syndrome.

Klinefelter's syndrome is characterized by abnormal karyotype 47, XXY and a phenotype associated with hypogonadism and gynecomastia. Often the disease can be diagnosed accidentally, when carrying out cytogenetic analysis in cases of a malignant blood disease. We present the clinical case of a patient diagnosed with acute myelomonoblastic leukemia-M4 Eo (AML- M4), where by means of classic cytogenetics a karyotype was found corresponding to Klinefelter's syndrome. Three induction courses of polychemotherapy wermade, which led to remission of the disease, documented both flowcytometrically and cytogenetically.

Flow cytometric investigation of CD40-CD40 ligand system in preeclampsia and normal pregnancy.

Our aim was to investigate the CD40-CD40 ligand system in preeclamptic women. We also studied CD62P and platelet-monocyte aggregates, which have been closely linked to the CD40-CD40L system. Platelet expression of CD40L and CD62P and expression of CD40 on monocytes and platelet-monocyte aggregates were determined by flow cytometry in whole blood from 23 preeclamptic women, 23 normotensive pregnant women, and 23 nonpregnant women. The preeclamptic women showed a significant increase in CD40L and CD62P on platelets and in CD40 on monocytes when compared with normotensive pregnant women and nonpregnant women (all P < .001). There was a significant increase in platelet-monocyte aggregates in preeclamptic women (P < .001) and normotensive pregnant women (P = .003) compared with nonpregnant women. Preeclampsia is associated with activation of the CD40-CD40L system. The activation of this system may contribute to the development or maintenance of the proinflammatory and prothrombotic milieu found in preeclampsia.

Upregulation of the CD40-CD40 ligand system in pre-eclampsia.

OBJECTIVE: To investigate the CD40-CD40 ligand (CD40L) system in women with pre-eclampsia. METHODS: Expression of CD40 on monocytes and expression of CD40 and CD40L on platelets were determined by whole blood flow cytometry in 23 women with pre-eclampsia and in 23 normotensive pregnant women. Serum levels of soluble CD40L in both groups of women were measured by enzyme-linked immunosorbent assay. RESULTS: There was a significantly higher expression of CD40 and CD40L on platelets and CD40 on monocytes in the women with pre-eclampsia compared with normotensive pregnant women (P<0.001 for all comparisons). The serum concentration of soluble CD40L was significantly higher in women with pre-eclampsia compared with normotensive pregnant women (P=0.012). CONCLUSION: Pre-eclampsia is associated with activation of the CD40-CD40L system. The activation of this system may contribute to the development or maintenance of the proinflammatory and prothrombotic responses, increased cytokine production, and endothelial cell dysfunction found in pre-eclampsia.

Anti-elastin antibodies and elastin turnover in normal pregnancy and recurrent pregnancy loss.

PROBLEM: The aim of this study was to investigate elastin turnover and autoimmunity in patients with a history of recurrent pregnancy loss (RPL) and during normal pregnancy. METHOD OF STUDY: Anti-alpha-elastin and anti-tropoelastin IgG and IgM antibodies were measured by a home-made ELISA in serum samples of 60 medically and obstetrically normal pregnant women, classified to three trimester groups, 18 female patients with RPL and 18 healthy non-pregnant women with a history of successful pregnancies. One way analyses of variance and Least Significant Difference method were used for a statistical analysis. RESULTS: Anti-alpha-elastin IgG autoantibodies were significantly decreased in the third trimester pregnant women. IgM anti-alpha-elastin autoantibodies were significantly decreased in all pregnancy groups compared with the controls. Synthesis/degradation ratio of elastin was significantly increased in the third trimester pregnancy group, suggesting decreased elastin degradation during this period of pregnancy. Comparing the RPL patients with the healthy non-pregnant controls showed a significantly increased anti-alpha-elastin IgG antibody and significantly decreased synthesis/degradation ratio in the patient's group, suggesting increased elastin degradation in RPL. CONCLUSION: Elastin degradation is decreased during normal pregnancy. Increased anti-elastin IgG antibodies may contribute to the pathogenesis of pregnancy losses.

Protective effect of U-74389G on paraquat induced pneumotoxicity in rats.

Paraquat is a very toxic herbicide and a dangerous pollutant of the environment. It forms reactive oxygen species and increases the lipid peroxidation in the pulmonary cells. Our aim in this study was to estimate the protective effects of the lazaroid U-74389G possessing antilipidperoxidation activity and membrane-stabilizing effect. The experiment was carried out with 96 male Wistar rats. Paraquat dichloride was administered orally at 80mg/kg. The lazaroid U-74389G was injected intraperitoneally twice - 2h before receiving the paraquat with 10mg/kg and four hours later with 5mg/kg. Isolated application of paraquat increased enzyme activities of lactate dehydrogenase (LDH) and acid phosphatase (AcP) and the total protein content in bronchoalveolar lavage fluid (BALF). In the same experimental group the number of polymorphonuclear cells (PMNs) in BALF is elevated significantly on days 1 and 3. The combined treatment with paraquat and U-74389G did not increase the total protein content and the number of PMNs and it elevated the enzyme activities of LDH and AcP significantly less than the alone application of paraquat. It is concluded that the lazaroid U-74389G reduces the pneumotoxic effects of paraquat, estimated by sensitive cytologic and biochemical markers in BALF. The protective effect of U-74389G is well-expressed until day 3 after the treatment.