Ambient fine particulate matter exposures and human early placental inflammation.

Few data regarding the levels of TNF-α, INF-γ and IL-10 in the cervical mucus of pregnant women with the past medicalhistory of chronic endometritis have been found. The abovementioned cytokines have the impact on the course of pregnancy as well as the processes of trophoblast invasion into the spiral arteries of the uterus. Deviations in their levels at the early stages of pregnancy may be associated with the development of preeclampsia at later stages.Purpose: to assess the levels of TNF, INF-γ and cytokine IL-10 in the cervical mucus of pregnant women with a past medicalhistory of chronic endometritis. Additionally, the study aims to determine their role in the development of preeclampsia andevaluate the eff ectiveness of comprehensive preconception treatment in preventing cytokine imbalance and the occurrence of gestational complications.Method and Materials. 135 pregnant women with the past medical history of chronic endometritis have been supervisedduring their pregnancy and received preconception treatment (Group I), as well as 168 women, whose pregnancy occurred in the presence of untreated chronic endometritis (Group II). The control group (CG) involved 20 healthy women. Preconception treatment included the administration of azithromycin, hormonal therapy with Femoston- Comb 2/10, and L-arginine aspartate in combination with folate prophylaxis. During the study, the principles of patient- centered care were followed in accordance with the requirements of the Tokyo Declaration of the World Medical Association, the International Recommendations of the Helsinki Declaration on Human Rights, the Convention on Human Rights and Biomedicine of the Council of Europe, the Laws of Ukraine, the Orders of the Ministry of Health of Ukraine and the requirements of the Ethical Code of the Ukrainian physician. The cytokine (TNF-α, INFγ, IL-10) analysis in the cervical mucus was performed at 5-, 17-18 and 32 weeks of pregnancy, using the enzyme- linked immunosorbent assay method with corresponding standard commercial reagent kits from the «Vector BEST» company. The obtained data were processed using mathematical statistical methods, calculating the mean sample values (M), variance (σ) and standard errors of the means (m). Student’s t-test was used for assessment and the likelihood ratio was calculated using the «STATISTICA» software (StatSoft Inc., USA).The paper is an excerpt from the initiative scientifi c research project of the Department of Obstetrics and Gynecology No.2 at Poltava State Medical University, entitled «Optimization of approaches to the management of pregnancy in women at high risk of obstetric and perinatal pathology» (State registration number 0122U201228, duration:10.2022-09.2027).Results. In pregnant women with a past medical history of chronic endometritis an increase in the levels of INF-γ in cervicalmucus by 2.1 times at 5-6 weeks (p<0.001), by 2.4 times at 17-18 weeks (p<0.001) and by 1.7 times at 32 weeks of pregnancy(p<0.001) compared to corresponding levels of this cytokine in healthy pregnant women, has been detected. Similarly, TNF-αwas by 4.3 times greater at 5-6 weeks of pregnancy compared to the values in the control group (p<0.001), by 3.3 times greater at 17-18 weeks of pregnancy (p<0.001) and by 4.4 times at 32 weeks of pregnancy (p<0.001). All pregnant women with a past medical history of chronic endometritis who had levels of INF-γ in the cervical mucus greater than 66.4 pg/ml and/or levels of TNF-α greater than 90.9 pg/ml at 5-6 weeks of pregnancy subsequently manifested preeclampsia (OR 2.01; 95 % CI [1.1-7.12]; p<0.05 and OR 1.8; 95 % CI [1.2-6.29]; p<0.05 respectively). The level of IL-10 in their cervical mucus was by 4 times higher than the control values at 5-6 weeks of pregnancy (p<0.0001); by 3.1 times higher at 17-18 weeks of pregnancy (p<0.0001) and by 3 times higher at 32 weeks of pregnancy (p<0.0001). This compensates for the increase in pro-infl ammatory cytokines, allowing the TNF-α/IL-10 ratio to remain at a level characteristic of healthy women throughout pregnancy. In treated women, the concentration of INF-γ is by 1.8 times lower than in untreated patients at 5-6 weeks of pregnancy (p<0.0001), by 2.1 times at 17-18 weeks of pregnancy (p<0.0001), and by 1.4 times at 32 weeks of pregnancy (p<0.0001). Similarly, TNF-α in cervical mucus was found to be lower by 3.6 times (p<0.01), 2.6 times (p<0.0001), and 4 times (p<0.001) respectively, in the specifi ed terms. This helps to avoid excessive production of the anti-infl ammatory cytokine IL-10.Conclusions. In women who got pregnant with untreated chronic endometritis, an increased production of cytokines INF-γand TNF-α at the early stages of pregnancy has been established. Comprehensive pregravidar treatment of chronic endometritis allows for the normalization of levels of anti-infl ammatory cytokines INF-γ and TNF-α at the beginning of gestation, which creates conditions for preventing the development of preeclampsia. This leads to a 1.9 times reduction in the frequency of this complication (OR 2.3; 95 % CI [1.25-4.31]; p<0.05), a 1.8 times decrease in the frequency of severe forms of preeclampsia (OR 4.64; 95 % CI [1.23-17.48]; p<0.05) and a delay in the average onset of its manifestations by 4.9 weeks (p<0.0001).

Changes in cytokine balance in pregnant women with chronic endometritis in the past medical history and their role in the development of preeclampsia

The incidence of chronic endometritis is particularly high in women with spontaneous abortions, especially habitual ones. There are insuffi cient data on the mechanisms of miscarriage in women whose pregnancy occurred along with this pathology. Aim: to assess the level of synthesis of cytokines and endometrial proteins in women with CE in the preconceptional stage and in the early stages of pregnancy; to identify pathogenetic aspects of the impact of imbalance of these substances on the processes of pregnancy loss; to assess the possibility of correcting the identifi ed changes in the preconceptional stage. Materials and methods. The study was conducted in 2 phases. In the fi rst phase, 426 women with CE were studied (168 patients (group I) were treated for CE in the preconception period, and the rest, 258 patients (group II), did not receive treatment). The control group consisted of 30 healthy women. The levels of cytokines TNF-a, INF-γ, and IL-10 in cervical mucus and glycodelin in menstrual blood were determined by enzyme- linked immunosorbent assay. In the second phase of the study, women who became pregnant were followed: 135 women from group I who received preconceptional treatment for CE; 168 women from group II who became pregnant along with untreated CE; and 20 healthy women from the control group who became pregnant and subsequently had no complications. At 5-6 weeks of gestation, serum glycodelin concentration and cervical content levelsof TNF-a, INF-γ and IL-10 were determined. The data were processed using mathematical statistical methods, Student’s t-test, Pearson’s correlation coeffi cient (r) and odds ratio were evaluated using the STATISTICA program of StatSoft Inc. (USA). The study adhered to the tenets of the Declaration of Helsinki. The study protocol was approved by the local ethics committee of PSMU for all women enrolled in this study. The article is extracted from the initiative scientifi c research project of the Obstetrics and Gynecology Department No 2 of the Poltava State Medical University «Optimization of approaches to pregnancy management in women at high risk of obstetric and perinatal pathology» (term: 2022-2027; state registration number 0122U201228).Results and Discussion. At the preconceptional stage, patients with CE showed a signifi cant decrease in glycodelin levels by 2.9 times (p&lt;0.05), an increase in proinfl ammatory cytokines (INF-γ by 2.8 times (p&lt;0.001), TNF-α by half (p&lt;0.001)), and a decrease in IL-10 by 2 times (p&lt;0.001) compared to the levels in healthy non-pregnant women. A decrease in the level of glycodelin in menstrual blood of women with CE is inversely correlated with an increase in the level of proinfl ammatory cytokines in cervical mucus (both INF-γ; r= –0.77; p&lt;0.05, and TNF-α; r= –0.69; p&lt;0.05). At 5-6 weeks of gestation, the level of serumglycodelin was 14.5 % lower (р˂0.05) in patients with pregestational untreated CE and 58.6 % lower (p&lt;0.001) in women with early pregnancy loss. The level of this protein in menstrual blood of women with CE before pregnancy was positively correlated with its concentration in serum at 5-6 weeks of pregnancy (r=0.61; p&lt;0.01). Such a relationship was also characteristic for INF-γ (r=0.68; p&lt;0.05) and TNF-α (r=0.78; p&lt;0.05). An inverse correlation was also found between a decrease in glycodelin levels in the blood of pregnant women with a history of untreated CE at 5-6 weeks of pregnancy and an increase in TNF-α (r= –0.63; p&lt;0.05) and INF-γ (r= –0.57; p&lt;0.05) in the cervical mucus of these pregnant women at this stage of pregnancy. After treatment for CE, both in the preconceptional stage and in early pregnancy, an increase in glycodelin (р˂0.001), a decrease in INF-γ (p&lt;0.05) and TNF-α (p&lt;0.01), and an increase in IL-10 concentration (р˃0.05) were observed. The incidence of spontaneous abortion before 22 weeks’ gestation decreased 1.9-fold in women who received preconception treatment (OR 2.79; CI 95 % [1.45-5.38]; p &lt; 0.05).Conclusions. In women with CE, there is a decrease in glycodelin synthesis and cytokine imbalance with an increase in proinfl ammatory cytokines: INF-γ (2.8-fold; р˃0.001) and TNF-α (twofold; p&lt;0.001). The preconceptional decrease in glycodelin synthesis correlates with a decrease in synthesis of this protein by decidual cells after pregnancy, as well as with the prevalence of INF-γ and TNF-α in early pregnancy in women with a history of CE. This sets the stage for impaired immune tolerance between the uterus and the fetus and is one of the leading causes of spontaneous abortion in women who become pregnant with untreated CE. Preconceptional treatment of CE prevents the formation of cytokine imbalance and increases glycodelin synthesis in the early stages of pregnancy, which protects the course of pregnancy and reduces the incidence of early preterm labor by 4.6 times. 

Prerequisites for early pregnancy loss in women with chronic endometritis

Background: Interleukin (IL) genes are essential for regulating the immune and inflammatory processes. Epidemiological studies suggest that polymorphisms in IL genes are associated with a higher risk of recurrent pregnancy loss (RPL). Objective: This study aimed to examine the association between RPL risk and IL gene polymorphisms. Materials and Methods: A comprehensive search of the literature was conducted using PubMed, Google Scholar and Embase to identify relevant studies published until May 30, 2024. A total of 58 studies involving 13,696 participants (both RPL cases and controls) were included. Pooled odds ratios and 95% confidence intervals were calculated using fixed- or random-effects models, as appropriate, with ReviewManager version 5.4, Cochrane RoB Tool 2 and G*Power 3.1 software. Results: The meta-analysis revealed significant correlations between RPL risk and genetic variations in IL-1β (-511T &gt; C), IL-6 (-174 G &gt; C) and IL-10 (-1082 A &gt; G and-592 C &gt; A), with statistical significance set at P &lt; 0.05. Ethnic subgroup analysis showed that IL-1β (-511T &gt; C) and IL-10 (-592 C &gt; A) variations were strongly associated with RPL risk in Asian populations. Interpretation: Our research suggests that genetic variations in IL-1β (-511T &gt; C), IL-6 (-174 G &gt; C) and IL-10 (-1082 A &gt; G and-592 C &gt; A) are associated with susceptibility to RPL. Limitation: Our meta-analysis concentrated exclusively on single-factor studies and did not consider potential confounding variables such as age, environmental influences and lifestyle, which could affect susceptibility to RPL. In addition, the lack of individual raw data prevented us from investigating gene–environment and gene–gene interactions or the influence of other polymorphisms and cytokines in our analysis. Protocol Registration: http://www.osf.io/qhbva. 

Influence of Interleukin Polymorphisms on the Risk of Recurrent Pregnancy Loss: A Systematic Review and Meta-analysis

Abstract Cytokines are a type of protein that play an important role in the immune response and can also affect many physiological processes in the body. Cytokine polymorphisms refer to genetic variations or mutations that occur within the genes that code for cytokines, which may affect the level of cytokine production and function. Some cytokine polymorphisms have been associated with an increased risk of developing certain diseases, while others may be protective or have no significant effect on health. In recent years, the role of cytokine polymorphisms in the development of recurrent pregnancy loss (RPL) has been studied. RPL or miscarriage is defined as the occurrence of two or more consecutive pregnancy losses before the 20th week of gestation. There are diverse causes leading to RPL, including genetic, anatomical, hormonal, and immunological factors. With regard to cytokine polymorphisms, a few of them have been found to be associated with an increased risk of RPL, for instance, variations in the genes that code for interleukin‐6, tumor necrosis factor‐alpha, and interleukin‐10. The exact mechanisms by which cytokine polymorphisms affect the risk of recurrent miscarriage are still being studied, and further research is essential to fully understand this complex condition. This brief review aims to summarize the recent literature on the association between cytokine polymorphisms and RPL. 

Association between cytokine polymorphisms and recurrent pregnancy loss: A review of current evidence.

Impact of TNF-α profile in recurrent pregnancy loss pathogenesis: A patient based study from Assam.

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Impact of TNF-α profile in recurrent pregnancy loss pathogenesis: A patient based study from Assam.