Abnormal Pregnancy Outcomes Research Articles

Single-cell transcriptomic analysis of decidual immune cell landscape in the occurrence of adverse pregnancy outcomes induced by Toxoplasma gondii infection

BackgroundToxoplasma gondii is an obligate intracellular parasite that can lead to adverse pregnancy outcomes, particularly in early pregnancy. Previous studies have illustrated the landscape of decidual immune cells. However, the landscape of decidual immune cells in the maternal–fetal microenvironment during T. gondii infection remains unknown.MethodsIn this study, we employed single-cell RNA sequencing to analyze the changes in human decidual immune cells following T. gondii infection. The results of scRNA-seq were further validated with flow cytometry, reverse transcription-polymerase chain reaction, western blot, and immunofluorescence staining.ResultsOur results showed that the proportion of 17 decidual immune cell clusters and the expression levels of 21 genes were changed after T. gondii infection. Differential gene analysis demonstrated that T. gondii infection induced the differential expression of 279, 312, and 380 genes in decidual NK cells (dNK), decidual macrophages (dMφ), and decidual T cells (dT), respectively. Our results revealed for the first time that several previously unknown molecules in decidual immune cells changed following infection. This result revealed that the function of maternal–fetal immune tolerance declined, whereas the killing ability of decidual immune cells enhanced, eventually contributing to the occurrence of adverse pregnancy outcomes.ConclusionsThis study provides valuable resource for uncovering several novel molecules that play an important role in the occurrence of abnormal pregnancy outcomes induced by T. gondii infection.Graphical

Repeated pregnancy losses with multiple aneuploidies and major genomic imbalance: A case report

Rationale: If one of the partners is having balanced autosomal translocation, it is usually observed that the offspring inherit either normal chromosomes, balanced translocation identical to one of the parent or unbalanced chromosomal rearrangements of the same parental chromosome having translocation. Concern: A unique case presented with history of 8 miscarriages for genetic counseling. The last abortus material evaluation showed monosomy of chromosome X (Turner syndrome) in all the analyzed cells. There was a history of infertility and also repeated second trimester abortions on the paternal side. On the maternal side, there was a history of intellectual disability. Diagnose: History of repeated abnormal pregnancy outcomes. Wife’s karyotype is normal; however, husband shows translocation between chromosome 4 and 22. Intervention: Peripheral blood sample around 3 mL was collected for karyotype. Embryo biopsy was done and DNA was extracted and processed for whole exome sequencing. Outcomes: Wife’s karyotype is normal and husband has translocation between chromosome 4 and 22. Surprisingly, the entire pregnancy outcome including embryo screening has different, complete or partial aneuploidies of chromosomes other than chromosome 4 and 22. Main lesson: Though the translocation in one of the parent is balanced, we have to think beyond traditional ways for evaluating a couple with repeated pregnancy loss as we cannot predict the errors at cell division. Option of in vitro fertilization and preimplantation genetic diagnosis in couples having balanced translocations should be discussed so that early intervention can prevent the agony of pregnancy loss.

The status and influencing factors of abnormal fetal pregnancy outcomes in 265 cases in China: a retrospective study.

With the advancement of prenatal diagnosis technology, the detection rate of fetal abnormalities continues to increase, imposing a significant burden on both society and families. A retrospective analysis of essential information about pregnant women, such as their pregnancy history and delivery details, is crucial for understanding the primary factors that influence pregnancy outcomes in women with fetal abnormalities. This analysis is of great significance for improving the level of pregnancy management and outcomes in pregnant women with fetal abnormalities. To retrospectively analyze the pregnancy outcomes of women with fetal abnormalities and explore the factors that influence these outcomes. Pregnant women's pregnancy outcomes were collected from the medical information system and through telephone follow-ups. The chi-square test and logistic regression were used to analyze the factors influencing pregnancy outcomes. Among 265 pregnant women diagnosed with fetal abnormalities, 190 chose to continue the pregnancy, while 75 chose to terminate it. Pregnant women with multiple fetal abnormalities (OR = 3.774, 95% CI [1.640-8.683]) were more likely to choose termination of pregnancy (TOP), and pregnant women who were advised to terminate their pregnancy or make a careful choice were more likely to terminate the pregnancy (OR = 41.113, 95% CI [11.028-153.267]). The number of organs involved in fetal abnormalities and treatment recommendations were identified as the primary factors influencing pregnancy outcomes. Improving awareness of maternal health care during pregnancy, early pregnancy screening technology, and a multidisciplinary diagnosis and treatment approach are of great significance in assisting pregnant women in making informed decisions and improving fetal prognosis.

MiR-135a-5p regulates window of implantation by suppressing pinopodes development and decidualization of endometrial stromal cells.

The window of implantation (WOI) is a brief period during which the endometrium is receptive to embryo implantation. This study investigated the relationship between miR-135a-5p and endometrial receptivity. Peripheral blood was collected on the day of ovulation and the 5th day after ovulation for high-throughput sequencing from women who achieved clinical pregnancy through natural cycle frozen embryo transfer. RT-qPCR assessed miR-135a-5p expression in the endometrium tissue or cells during the mouse implantation window or decidualization. Scanning electron microscopy was utilized to observe pinopode morphology and quantity in mice overexpressing miR-135a-5p during the WOI. Human endometrial stromal cells (HESC) and artificial induction of mouse uterine decidualization were used to explore whether miR-135a-5p overexpression inhibits decidualization by regulating HOXA10 and BMPR2. Furthermore, the impact of miR-135a-5p on HESC proliferation and HTR8/SVneo invasion was explored. A total of 54 women were enrolled in the study. bioinformatics analysis and animal models demonstrated that miR-135a-5p was significantly downregulated during the WOI, and its high expression can lead to abnormal pregnancy outcomes. Overexpression of miR-135a-5p resulted in the absence of pinopode in mouse endometrial tissue during the WOI. High miR-135a-5p levels were found to potentially inhibit endometrial tissue decidualization by downregulating HOXA10 and BMPR2 expression. Finally, CEBPD was identified as a potential regulator of miR-135a-5p, which would explain the decreased miR-135a-5p expression during the WOI. MiR-135a-5p expression is significantly downregulated during the WOI. High miR-135a-5p levels suppress pinopode development and endometrial tissue decidualization through HOXA10 and BMPR2, contributing to inadequate endometrial receptivity.

YOLK SAC DIAMETER AND EMBRYONIC HEART RATE AS PROGNOSTIC FACTORS OF FIRST TRIMESTER PREGNANCY OUTCOME

Objective: Yolk sac is the primary source of exchange between the embryo and the mother before placental circulation and during organogenesis. Yolk sac has immunologic, metabolic, nutritive, endocrine, secretory, excretory and hematopoietic functions. Embryonic heart rate is seen after the appearance of foetal node at 7 w by TAS and 6 w by TVS. Studies have been conducted to establish the importance of yolk sac and EHR in pregnancy outcome. The prognostic significance of the yolk sac for the pregnancy outcome has been assessed with TVS. To measure yolk sac diameter and embryonic heart rate in early pregnancy (less than 10 weeks), to correlate yolk sac measurement and embryonic heart rate individually as prognostic factors for first trimester outcome and to evaluate the measurements in combination as a prognostic marker of first trimester pregnancy outcome. In view of this, the present study was undertaken.
 Methods: 108 patients attending OPD of Kempe Gowda institute of Medical Sciences Hospital, between 6 to 9 w of gestation, were evaluated with transvaginal sonography and measurements such as CRL, MSD and YSD were taken.
 Results: The mean age of the study population was 25 y and 88 % of the study population belonged to 20-30 y. 55.6 % of the study population were primigravida. Incidence of abnormal pregnancy outcome was 18.5%. The probability of abnormal outcome increased with the increase in gravidity of the patient (P= 0.890). There was a significant positive comparison of CRL (P= 0.223), GS (P= 0.251) and YSD (P= 0.016). Yolk sac diameter in the first trimester significantly correlates with the pregnancy outcome. An enlarged yolk sac is associated with an increased risk of preterm delivery. Our study influences the pregnancy outcome by the Embryonic heart rate. Foetal bradycardia is an impending sign of foetal death due to chromosomal abnormalities (Trisomy 18), foetal tachycardia featuring Trisomy 21.
 Conclusion: Yolk sac diameter and embryonic heart rate in the first trimester significantly correlates with the first trimester pregnancy outcome. Thus, the present study indicates that the yolk sac size and the embryonic heart rate is a reliable, beneficial and cost-effective in predicting first-trimester pregnancy outcome. The measurement of the secondary yolk sac diameter between 5th to 9th week of gestation can be used as a valuable tool to predict early pregnancy outcome.

Heterogeneity in the prevalence of subclinical malaria, other co-infections and anemia among pregnant women in rural areas of Myanmar: a community-based longitudinal study

BackgroundDue to the low prevalence of clinically suspected malaria among pregnant women in Myanmar, little is known about its impact on mothers and newborns. Helminth and Human Immuno-deficiency Virus (HIV) co-infections cause anemia in pregnant women. This study assessed the prevalence of subclinical malaria and co-infections among pregnant women, and its association with adverse outcomes of pregnancy in the presence of infection.MethodsA prospective longitudinal study was conducted in 12 villages in two townships in Myanmar between 2013 to 2015. A total of 752 pregnant women, with a mean age of 27 years, were enrolled and followed up once a month until six weeks after childbirth. Prevalence ratio was calculated in the multivariable analysis.ResultsThe prevalence of subclinical malaria as measured by nested PCR was 5.7% for either P. falciparum or P. vivax, 2.7% prevalence of P. falciparum and 2.8% prevalence of P. vivax. Helminth infections were prevalent in 17% of women, and one woman with an HIV infection was found in our study. The burden of anemia was high, with an overall prevalence of 37% with or without helminth infection, 42% of the women were malaria positive and 43% had dual infections (both malaria and helminth). Only 11 abnormal pregnancy outcomes (7 stillbirths, 2 premature, 2 twins) were identified. Poisson regression showed that women in their first trimester had a 2.9 times higher rate of subclinical malaria compared to women in the third trimester (PR:2.9, 95%CI 1.19, 7.31, p = 0.019), women who were enrolled during the wet season were 2.5 times more likely to be malaria positive than the women enrolled in the dry season (PR: 2.5, 95%CI 1.27, 4.88, p = 0.008), and the malaria positivity rate decreased by 5% when increased in one year of woman’s age (PR:0.95, 95%CI 0.91, 0.99, p = 0.02). In the multivariable regression, the age of respondents was the only significant factor associated with subclinical malaria in pregnancy.ConclusionsA comprehensive approach of integrating interventions for malaria, anemia, and helminths should be delivered during antenatal care services for pregnant women in rural areas of Myanmar.

Pregnancy Outcome of Confined Placental Mosaicism: Meta-analysis of Cohort Studies

ABSTRACT Confined placental mosaicism (CPM) is a condition in which there is chromosomal abnormality in the placenta that is not present in the fetus. Confined placental mosaicism has historically been most often identified following a first-trimester chorionic villus sampling (CVS), in which there are 2 different cell lines in the placenta but a normal karyotype in the fetus based on amniocentesis or neonatal blood. As the outcome for CPM pregnancies is still debated, including the potential for adverse pregnancy and postnatal outcomes, this study aimed to evaluate the rates of adverse neonatal and obstetrical outcomes in CPM-diagnosed pregnancies, as compared with unaffected matched controls. This meta-analysis was performed in accordance with an a priori designed protocol and was registered with the PROSPERO (International Prospective Register of Systematic Reviews) database. A search of EMBASE and MEDLINE databases from 1980 to February 2022 was performed. Included articles were published in the English language and were observational studies including singleton CPM-diagnosed pregnancies (whose controls were unaffected and with normal karyotype). Excluded were all reviews, case reports, and congress abstracts. In addition, high-risk or positive cell-free DNA screening (cfDNA) cases followed by diploid amniotic cells were excluded (because of the different methodology, which may have an effect on the analysis). Because of the paucity of data regarding mosaicism in submicroscopic copy number variants, these abnormalities were also excluded from the analysis. Primary outcomes included the occurrence of the following: termination of pregnancy, major fetal defects (as defined by the Centers for Disease Control and Prevention), small for gestational age (SGA) neonate with birth weight (BW) <10th centile and neonatal SGA with BW less than the third centile, preterm birth (PTB), hypertensive disorders, admission to a neonatal intensive care unit, intrauterine fetal demise at <24 weeks' gestation, and >24 weeks' gestation stillbirth. All other abnormal pregnancy outcomes were searched for, including PTB, obstetrical cholestasis, amniotic infection, gestational diabetes, cesarean delivery, amniotic infection, preterm prelabor rupture of membranes, and neonatal mortality or morbidity. Of 310 retrieved articles, 80 studies were assessed for eligibility, and 8 retrospective matched cohort studies were included. The results of the meta-analysis showed that women with CPM had a higher risk of adverse pregnancy outcomes than those without CPM. The most common adverse outcomes were fetal growth restriction (FGR), PTB, and stillbirth. The risk of FGR was significantly higher in women with CPM, with an odds ratio (OR) of 3.60 (95% confidence interval [CI], 2.40–5.39). Similarly, the risk of PTB was higher in women with CPM, with an OR of 2.64 (95% CI, 1.90–3.67), and the risk of stillbirth was also increased, with an OR of 2.58 (95% CI, 1.51–4.42). Scarcity of reporting for other obstetrical neonatal and obstetrical outcomes hindered further conclusions. In subgroup analysis, the risk of delivering an SGA infant was 3-fold higher for CPM when trisomy 16 was excluded and 11-fold higher for trisomy 16 specifically compared with unaffected controls. The authors acknowledge that the meta-analysis has several limitations, including the heterogeneity of the included studies, the lack of information on the specific type and extent of CPM in each case, and the potential for publication bias. Nevertheless, the study provides valuable insights into the pregnancy outcomes of women with CPM and highlights the need for further research to improve our understanding of this condition. Overall, this meta-analysis suggests that women with CPM are at increased risk of adverse pregnancy outcomes, particularly FGR, PTB, and stillbirth. The findings highlight the importance of early detection of CPM and close monitoring of pregnancies in women with this condition. The study also emphasizes the need for further research to better understand the underlying mechanisms of CPM and to identify effective interventions to improve pregnancy outcomes in affected women.

A study of yolk sac diameter in predicting abnormal outcome of pregnancy in rural hospital

Introduction: Early pregnancy loss is the most common complication of early pregnancy. First trimester is crucial, since 80% of pregnancy losses occur spontaneously during this period. There is great difficulty in reliably anticipating which pregnancies will terminate in abortion. The yolk sac is the first extra embryonic structure that becomes sonographically visible within the gestational sac. Aims and Objectives of the present study is to evaluate the size of yolk sac as a predictor of pregnancy outcome.Material and Methods: The present Observational Prospective study was conducted on 104 pregnant woman with gestational age 6 to 10 weeks attending OPD in the department of obstetrics and gynaecology at MVJ Medical college and research hospital from December 2020 to December 2022 Results: In present study Mean age of the study participants was 25.31+4.483 and mean values of radiological findings were gestational age (days)56.28days ±8.120, MSD was 2.2545±0.99, YSD was 2.25±0.99, CRL was 1.29±0.66 and HR was 156.61±13.453. Majority of the study participants 71.2% had normal perinatal outcome. There is steady increase in YSD mean value and difference observed is statistically significant. Statistically significant differences were observed between normal and abnormal perinatal outcome.Conclusion: Abnormalities of YS size or shape, early regression or absence can be used as poor predictor of first trimester pregnancy outcome, even before studying the fetal morphology.

Prevalence of Anemia among Working Pregnant Women and Their Pregnancy Outcome

The main focus of this study was to discover prevalence of anemia among working pregnant women and their pregnancy outcome in Bangladesh. A cross-sectional observational study methodology and a multi-stage random sampling technique were chosen to select the study place. Estimated sample size was 410. A prepared and pre-tested questionnaire was used for data collection. Data was analyzed by Statistical Package for Social Sciences (SPSS) version 20. Both analytical and descriptive components were used for analysis. Chi-square test was used to find the association. The results were presented with some tabular form as well as in a descriptive manner. About three-fourth of the pregnancies resulted in normal pregnancy outcome, while 23.6% of the surveyed pregnant women experienced abnormal pregnancy outcomes i.e., preterm delivery (0.5%), low-birth weight baby (22.9%) and stillbirth (0.2%). Prevalence of anemia was 65.9%, with 45.4%, 19.8% and 0.5% of the women being mildly, moderately and severely anemic. Analysis reveals that abnormal pregnancy (i.e. Low birth weight, preterm delivery and still birth) outcomes were relatively higher among older mothers and women having lower level of educational qualifications. Severity of anemia during pregnancy had a statistically significant association with abnormal pregnancy outcomes (p=.000). Positive correlation was also found between monthly family income and weight of the baby which was statistically significant (p=0.011).

Sensitivity of uterine artery Doppler pulsatility index in screening for adverse pregnancy outcome in first and second trimesters.

In a poor resource country where screening for adverse pregnancy outcomes using maternal biomarkers seems unattainable, there is a need to search for credible alternatives. This study is, therefore, aimed at determining the sensitivity of uterine artery Doppler pulsatility index (UtAD-PI) in predicting pregnancy outcomesin the first and second trimesters and to establish any statistical difference in mean UtAD-PI in first and second trimesters screening of women with normal and abnormal pregnancy outcomes respectively. This clinical-based, longitudinal, and unpaired cohort study involved 500 pregnant women, who were screened for adverse outcomes using UtAD-PI and delivered in the hospital. These were divided into two groups, each having a training set and a test set. The training set was used to generate the receiver operator characteristic curve and cut-off point while the test set was used to test for sensitivity and specificity of the Ut-ADI in each trimester. The sensitivity and specificity of UtAD-PI in first-trimester screening are 97% and 76.5% while second-trimester gave sensitivity and specificity of 57.5% and 63.3% respectively. The uterine artery Doppler pulsatility index shows statistically significant differences between normal pregnancy and pregnancy with adverse outcomes (p-value = 0.000). The uterine artery Doppler pulsatility index is a good screening tool for adverse pregnancy outcomes. First-trimester screening of patients for adverse outcomes is more sensitive than the second-trimester screening using UtAD-PI. There is also a statistically significant difference between mean UtAD-PI between normal pregnancy and pregnancy with adverse pregnancy outcomes.

Role of Serum β-hCG and First Trimester Ultrasonographic Parameters in Predicting Mid-trimester Pregnancy Outcomes: A Prospective Cohort Study

Introduction: One of the concerns in pregnant women is the risk of miscarriage and the psychological sequelae that follow. Screening in early pregnancy can identify future miscarriages in asymptomatic pregnancies. Aim: To study the role of serum Beta-Human Chorionic Gonadotropin (β-hCG) doubling and ultrasonic parameters like Yolk Sac Diameter (YSD), Gestational Sac Diameter (GSD), and Crown-Rump Length (CRL) in predicting mid-trimester pregnancy outcomes. Materials and Methods: A prospective cohort study was conducted at SRM Medical College and Hospital in Tamil Nadu, India, among 381 antenatal women between 6-10 weeks of gestation for a period of two years from December 2017 to July 2019. At baseline, parameters like serum β-hCG doubling titer at 48 hours and ultrasound parameters like YSD, GSD, and CRL were evaluated. The participants were followed-up until 20 weeks of gestation. The results were statistically analysed using sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV). Results: The mean age of the women included in the study was 25.89±4.2 years, with the majority of women belonging to the 21-29 years age group. Among the enrolled pregnant women, 347 had normal outcomes while 34 experienced pregnancy failure. The results indicated that β-hCG was the strongest predictor of pregnancy outcomes with a sensitivity of 52.9%, specificity of 100%, PPV of 100%, and NPV of 95.6%. YSD predicted loss rates with a sensitivity of 50%, specificity of 97.1%, PPV of 62.9%, and NPV of 95.2%. GSD predicted miscarriage with a sensitivity of 17.6%, specificity of 97.4%, PPV of 40%, and NPV of 92.3%. CRL predicted miscarriage with a sensitivity of 30.5%, specificity of 97.9%, PPV of 61.1%, and NPV of 93.2%. Conclusion: β-hCG, YSD, GSD, and CRL were found to be statistically significant in predicting abnormal pregnancy outcomes. Among the four, β-hCG proved to be the best predictor.

Fetuses with increased nuchal translucency before 11 weeks are at risk of abnormal pregnancy outcome

An increased nuchal translucency (NT) ≥3.5mm is a reliable marker for chromosomal- and structural anomalies between 11 and 13+6 weeks' gestation. Little is known about its performance as a screening tool before 11 weeks.

Effect of B7-H4 downregulation induced by Toxoplasma gondii infection on dysfunction of decidual macrophages contributes to adverse pregnancy outcomes

BackgroundToxoplasma gondii infection during pregnancy can lead to fetal defect(s) or congenital complications. The inhibitory molecule B7-H4 expressed on decidual macrophages (dMφ) plays an important role in maternal–fetal tolerance. However, the effect of B7-H4 on the function of dMφ during T. gondii infection remains unclear.MethodsChanges in B7-H4 expression on dMφ after T. gondii infection were explored both in vivo and in vitro. B7-H4-/- pregnant mice (pregnant mice with B7-H4 gene knockout) and purified primary human dMφ treated with B7-H4 neutralizing antibody were used to explore the role of B7-H4 signaling on regulating the membrane molecules, synthesis of arginine metabolic enzymes and cytokine production by dMφ with T. gondii infection. Also, adoptive transfer of dMφ from wild-type (WT) pregnant mice or B7-H4-/- pregnant mice to infected B7-H4-/- pregnant mice was used to examine the effect of B7-H4 on adverse pregnancy outcomes induced by T. gondii infection.ResultsThe results illustrated that B7-H4-/- pregnant mice infected by T. gondii had poorer pregnancy outcomes than their wild-type counterparts. The expression of B7-H4 on dMφ significantly decreased after T. gondii infection, which resulted in the polarization of dMφ from the M2 toward the M1 phenotype by changing the expression of membrane molecules (CD80, CD86, CD163, CD206), synthesis of arginine metabolic enzymes (Arg-1, iNOS) and production of cytokines (IL-10, TNF-α) production. Also, we found that the B7-H4 downregulation after T. gondii infection increased iNOS and TNF-α expression mediated through the JAK2/STAT1 signaling pathway. In addition, adoptive transfer of dMφ from a WT pregnant mouse donor rather than from a B7-H4-/- pregnant mouse donor was able to improve adverse pregnancy outcomes induced by T. gondii infection.ConclusionsThe results demonstrated that the downregulation of B7-H4 induced by T. gondii infection led to the dysfunction of decidual macrophages and contributed to abnormal pregnancy outcomes. Moreover, adoptive transfer of B7-H4+ dMφ could improve adverse pregnancy outcomes induced by T. gondii infection.Graphical

Tim-3 downregulation by Toxoplasma gondii infection contributes to decidual dendritic cell dysfunction

BackgroundWomen in early pregnancy infected by Toxoplasma gondii may have severe adverse pregnancy outcomes, such as spontaneous abortion and fetal malformation. The inhibitory molecule T cell immunoglobulin and mucin domain 3 (Tim-3) is highly expressed on decidual dendritic cells (dDCs) and plays an important role in maintaining immune tolerance. However, whether T. gondii infection can cause dDC dysfunction by influencing the expression of Tim-3 and further participate in adverse pregnancy outcomes is still unclear.MethodsAn abnormal pregnancy model in Tim-3-deficient mice and primary human dDCs treated with Tim-3 neutralizing antibodies were used to examine the effect of Tim-3 expression on dDC dysfunction after T. gondii infection.ResultsFollowing T. gondii infection, the expression of Tim-3 on dDCs was downregulated, those of the pro-inflammatory functional molecules CD80, CD86, MHC-II, tumor necrosis factor-α (TNF-α), and interleukin-12 (IL-12) were increased, while those of the tolerant molecules indoleamine 2,3-dioxygenase (IDO) and interleukin-10 (IL-10) were significantly reduced. Tim-3 downregulation by T. gondii infection was closely associated with an increase in proinflammatory molecules and a decrease in tolerant molecules, which further resulted in dDC dysfunction. Moreover, the changes in Tim-3 induced by T. gondii infection further reduced the secretion of the cytokine IL-10 via the SRC-signal transducer and activator of transcription 3 (STAT3) pathway, which ultimately contributed to abnormal pregnancy outcomes.ConclusionsToxoplasma gondii infection can significantly downregulate the expression of Tim-3 and cause the aberrant expression of functional molecules in dDCs. This leads to dDC dysfunction, which can ultimately contribute to abnormal pregnancy outcomes. Further, the expression of the anti-inflammatory molecule IL-10 was significantly decreased by Tim-3 downregulation, which was mediated by the SRC-STAT3 signaling pathway in dDCs after T. gondii infection.

A novel 2B4 receptor leads to worse pregnancy outcomes by facilitating TNF-α and IFN-γ production in dNK cells during Toxoplasma gondii infection

BackgroundInfections are a major threat to human reproductive health because they can induce pregnancy failure, including recurrent abortion, stillbirth, and preterm birth. Toxoplasma gondii (T. gondii) infection can result in adverse pregnancy outcomes by affecting certain immune molecules and cytokines. However, the detailed mechanisms behind T. gondii-induced pregnancy failure are poorly understood.MethodsToxoplasma gondii-infected wild-type (WT) pregnant mice and 2B4 knockout (2B4−/−) pregnant mice were established for in vivo study. Human decidual natural killer (dNK) cells were cultured for in vitro study. Abnormal pregnancy outcomes were observed, and the expression of 2B4, functional molecules (CD69, CD107a, tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ]), and signaling molecules (SHP-2, Fyn, p-ERK, p-P38) in dNK cells were detected by flow cytometry, Western blot, reverse transcriptase polymerase chain reaction (RT-PCR), and/or immunofluorescence. The direct interactions (2B4 interacts with SHP-2 and Fyn; SHP-2 interacts with p-P38 and 2B4; Fyn interacts with p-ERK and 2B4) were verified by co-immunoprecipitation (co-IP) in NK-92 cells.ResultsHere, results showed that 2B4 was significantly downregulated after T. gondii infection. Subsequently, infected 2B4−/− pregnant mice displayed worse pregnancy outcomes compared with infected WT pregnant mice. Also, increased TNF-α and IFN-γ expression and elevated dNK cell cytotoxicity were found in 2B4−/− pregnant mice during T. gondii infection. In contrast, reduced TNF-α and IFN-γ expression and decreased human dNK cell activity were found following 2B4 activation during T. gondii infection. Interestingly, results showed that 2B4 binds to adaptor SHP-2 or Fyn, which then triggers different signaling pathways to regulate TNF-α and IFN-γ expression in dNK cells during T. gondii infection. Further, SHP-2 binds 2B4 and p-P38 directly after 2B4 activation, which generates an inhibitory signal for TNF-α and IFN-γ in NK-92 cells. In addition, Fyn can bind to 2B4 and p-ERK after activation of 2B4, thereby inhibiting TNF-α and IFN-γ expression in NK-92 cells following T. gondii infection.ConclusionsThese data suggest that 2B4 may be a novel danger-signaling molecule that is implicated in pregnancy failure during T. gondii infection. Unraveling the mechanism by which 2B4 regulates dNK cell activity will provide novel insights to aid our understanding of T. gondii-induced adverse pregnancy outcomes.Graphical

The mediating role of maternal metabolites between lipids and adverse pregnancy outcomes of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, and the demographics of pregnant women have changed in recent decades. GDM is a metabolic disease with short- and long-term adverse effects on both pregnant women and newborns. The metabolic changes and corresponding risk factors should be of great significance in understanding the pathological mechanism of GDM and reducing the incidence of adverse pregnancy outcomes in patients with GDM. The well-known GDM-associated lipids used in clinical tests, such as triglyceride (TG), are thought to play a major role in metabolic changes during GDM, which have a potential causal relationship with abnormal pregnancy outcomes of GDM. Therefore, this study analyzed the relationship between clinical lipid indicators, metabolic profiles, and abnormal pregnancy outcomes in GDM through mediation analysis. By constructing a metabolic atlas of 399 samples from GDM patients in different trimesters, we efficiently detected the key metabolites of adverse pregnancy outcomes and their mediating roles in bridging abnormal lipids and adverse pregnancy outcomes in patients with GDM. Our study confirmed that TG and total cholesterol were independent risk factors for adverse pregnancy outcomes in patients with GDM. Several key metabolites as mediators (e.g., gamma-linolenic acid, heptadecanoic acid, oleic acid, palmitic acid, and palmitoleic acid) have been identified as potential biomarkers for adverse pregnancy outcomes in patients with GDM. These metabolites mainly participate in the biosynthesis of unsaturated fatty acids, which may shed new light on the pathology of GDM and provide insights for further exploration of the molecular mechanisms underlying adverse pregnancy outcomes.

Predicting the Outcome of a Pregnancy of Unknown Location: What Can the Endometrial Stripe Thickness Reveal?

Objective: To investigate the role of the uterine endometrial thickness and sonographic pattern as potential predictors for a pregnancy with an unknown location (PUL) and its possible outcomes. Materials and Methods: A convenient sample of 330 symptomatic extra preposition female patients were enrolled in this study with a diagnosis of PUL. The clinical variables of endometrial stripe thickness and endometrial sonographic pattern were determined with transvaginal sonography. These sonographic examinations (it seems that examination in this context is a countable noun) were conducted during the first 24 hours of referral, and their predictive values for PUL outcomes (normal intrauterine pregnancy (IUP), ectopic pregnancy (EP), and pregnancy loss) were assessed after clinical follow-up sessions provided a definite outcome. The statistical significance was set a priori at a P value < .05. Results: The mean initial endometrial stripe thickness among participants, with a normal IUP, was more than those patients with an abnormal pregnancy outcome ( P < .05). The optimum cut-off value for predicting a an EP, compared to a normal IUP was 11 mm and had a sensitivity of 73.3% and specificity of 39% ( P < .001). These results also demonstrated no statistically significant relationship between the PUL outcome and the categories of endometrial sonographic pattern ( P = .15). Conclusion: In this large cohort of patients, the endometrial stripe thickness of more than 11 mm, among those who were symptomatic and deemed as PUL, had the potential to predict ectopic pregnancy as an unlikely diagnosis.

B7-H4 reduction induced by Toxoplasma gondii infection results in dysfunction of decidual dendritic cells by regulating the JAK2/STAT3 pathway

BackgroundPrimary infection of Toxoplasma gondii can cause serious abnormal pregnancy outcomes such as miscarriage and stillbirth. Inhibitory molecule B7-H4 is abundantly expressed in dendritic cells (DCs) and plays an important role in maintaining immune tolerance. However, the role of B7-H4 in decidual DCs (dDCs) in T. gondii-induced abnormal pregnancy outcomes is not clear.MethodsWe established T. gondii-infected abnormal pregnancy model in wild-type (WT) and B7-H4 knockout (B7-H4−/−) pregnant mice in vivo and cultured primary human dDCs in vitro. The abnormal pregnancy outcomes were observed and the expression of B7-H4, functional molecules (CD80, CD86, and MHC-II or HLA-DR), indoleamine 2,3-dioxygenase (IDO), cytokines (IL-10 and IL-12), and signaling molecules JAK2/STAT3 in dDCs was detected by flow cytometry and Western blot.ResultsOur results showed that T. gondii infection significantly decreased B7-H4 expression in dDCs. In addition, B7-H4−/− infected pregnant mice showed much more severe abnormal pregnancy outcomes than their counterparts. Importantly, B7-H4−/− infection further regulated the expression of molecules (CD80, CD86, and MHC-II or HLA-DR), enzyme IDO, and cytokines (IL-10 and IL-12) in dDCs. We further discovered that B7-H4−/− infection impairs the JAK2/STAT3 pathway, contributing to dDC dysfunction.ConclusionsTaken together, the results show that reduction of B7-H4 by T. gondii infection significantly modulates the decrease in cytokine IL-10 and enzyme IDO and the increase in cytokine IL-12, contributing to dDC dysfunction. Moreover, the JAK2/STAT3 pathway is involved in the regulation of B7-H4 by T. gondii infection and in the subsequent IDO and cytokine production, which ultimately contributes to abnormal pregnancy outcomes.Graphical

Ultrasound Technique Based on Liposome Nanovesicles in the Evaluation of Abnormal Pregnancy Outcomes in Diabetic Women

Gestational diabetes mellitus (GDM) refers to the first occurrence or detection of glucose tolerance abnormalities during pregnancy, including cases that may have existed before pregnancy but have not been detected. It is one of the common complications during pregnancy. In recent years, the incidence of GDM is on the rise. The most common complication of GDM is macrosomia, which often causes dystocia, neonatal asphyxia, birth injury and postpartum bleached blood. Early diagnosis, appropriate treatment and maintenance of reasonable and stable blood glucose concentration can significantly reduce the incidence of complications. The purpose of this study was to investigate the application of ultrasound technique based on liposome nano-vesicles in the assessment of abnormal pregnancy outcomes in diabetic pregnant women. Objective: To investigate the value of ultrasound in the examination of fetal growth in pregnant women with gestational diabetes mellitus. Methods a total of 100 pregnant women with gestational diabetes admitted to the hospital were selected as the research objects, and the clinical data of ultrasound examination were retrospectively analyzed. According to the newborn weight, they were divided into control group (normal fetus group) and observation group (giant fetus group). The growth of fetuses in the two groups was compared, and the predictive value of each measurement index to the weight of giant fetus was analyzed.Multiple regression analysis showed that LL, AC and FL played a decisive role in fetal weight, with statistically significant differences (P<0.05). Conclusion Ultrasonography is of great value in predicting fetal growth in pregnant women with gestational diabetes mellitus and can be widely used.

The 16-week sonographic findings in fetuses with increased nuchal translucency and a normal array

Objective The aim of this prospective study is to evaluate the performance of the intermediate 16-week ultrasound in fetuses with increased nuchal translucency (NT) and a normal chromosomal microarray analysis (CMA). Methods During a one-year period, a detailed ultrasound was performed at 16 week’ gestation for patients with an increased NT (≥3.5 mm) and normal CMA. Pregnancy work-up included a traditional 22-week ultrasound scan, an echocardiography, and the option of a 10-gene Rasopathy panel after a normal 16-week scan. Abnormal findings and pregnancy outcomes were collected and analyzed. Results In 52 fetuses with an isolated increased NT and normal CMA, 14 (26.5%) were noted to have structural defects on the 16-week ultrasound. Intrauterine fetal death occurred in one (1.9%) case identified by the 16-week scan. Of the remaining 37 cases, six opted for a RASopathy panel. In this group, one case of Noonan syndrome was detected. One case of unilateral duplex kidney had not been found until the 22-week scan. One case of fetal growth restriction was identified in the third trimester. The remaining 34 cases proceeded with normal ultrasound to term. Conclusion The 16-week ultrasound scan performed on fetuses with increased NT and normal CMA could detect the majority of structural abnormalities that are expected to be identified traditionally at 20–24 weeks.