Placental galectins regulate innate and adaptive immune responses in pregnancy

IntroductionGalectins are master regulators of maternal immune responses and placentation in pregnancy. Galectin-13 (gal-13) and galectin-14 (gal-14) are expressed solely by the placenta and contribute to maternal-fetal immune tolerance by inducing the apoptosis of activated T lymphocytes and the polarization of neutrophils toward an immune-regulatory phenotype.Furthermore, their decreased placental expression is associated with pregnancy complications, such as preeclampsia and miscarriage. Yet, our knowledge of the immunoregulatory role of placental galectins is incomplete.MethodsThis study aimed to investigate the effects of recombinant gal-13 and gal-14 on cell viability, apoptosis, and cytokine production of peripheral blood mononuclear cells (PBMCs) and the signaling pathways involved.ResultsHerein, we show that gal-13 and gal-14 bind to the surface of non-activated PBMCs (monocytes, natural killer cells, B cells, and T cells) and increase their viability while decreasing the rate of their apoptosis without promoting cell proliferation. We also demonstrate that gal-13 and gal-14 induce the production of interleukin (IL)-8, IL-10, and interferon-gamma cytokines in a concentration-dependent manner in PBMCs. The parallel activation of Erk1/2, p38, and NF-ĸB signaling evidenced by kinase phosphorylation in PBMCs suggests the involvement of these pathways in the regulation of the galectin-affected immune cell functions.DiscussionThese findings provide further evidence on how placenta-specific galectins assist in the establishment and maintenance of a proper immune environment during a healthy pregnancy

Concordance of the risk of neonatal respiratory morbidity assessed by quantitative ultrasound lung texture analysis in fetuses of twin pregnancies

To evaluate the concordance of the risk of neonatal respiratory morbidity (NRM) assessed by quantitative ultrasound lung texture analysis (QuantusFLM) between twin fetuses of the same pregnancy. Prospective study conducted in twin pregnancies. There was good concordance of the risk of NRM between twins 34.0 weeks. From 30.0 to 33.6 weeks 26.5% of the twin pairs had discordant results, with moderate concordance of the risk of NRM

Prediction of Neonatal Respiratory Morbidity Assessed by Quantitative Ultrasound Lung Texture Analysis in Twin Pregnancies

The objective of this study was to evaluate the performance of quantitative ultrasound of fetal lung texture analysis in predicting neonatal respiratory morbidity (NRM) in twin pregnancies. This was an ambispective study involving consecutive cases. Eligible cases included twin pregnancies between 27.0 and 38.6 weeks of gestation, for which an ultrasound image of the fetal thorax was obtained within 48 h of delivery. Images were analyzed using quantusFLM® version 3.0. The primary outcome of this study was neonatal respiratory morbidity, defined as the occurrence of either transient tachypnea of the newborn or respiratory distress syndrome. The performance of quantusFLM® in predicting NRM was analyzed by matching quantitative ultrasound analysis and clinical outcomes. This study included 166 images. Neonatal respiratory morbidity occurred in 12.7% of cases, and it was predicted by quantusFLM® analysis with an overall sensitivity of 42.9%, specificity of 95.9%, positive predictive value of 60%, and negative predictive value of 92.1%. The accuracy was 89.2%, with a positive likelihood ratio of 10.4, and a negative likelihood ratio of 0.6. The results of this study demonstrate the good prediction capability of NRM in twin pregnancies using a non-invasive lung texture analysis software. The test showed an overall good performance with high specificity, negative predictive value, and accuracy

The amniotic fluid proteome predicts imminent preterm delivery in asymptomatic women with a short cervix

Abstract Preterm birth, the leading cause of perinatal morbidity and mortality, is associated with increased risk of short- and long-term adverse outcomes. For women identified as at risk for preterm birth attributable to a sonographic short cervix, the determination of imminent delivery is crucial for patient management. The current study aimed to identify amniotic fluid (AF) proteins that could predict imminent delivery in asymptomatic patients with a short cervix. This retrospective cohort study included women enrolled between May 2002 and September 2015 who were diagnosed with a sonographic short cervix ( 1.5 for each). The sensitivity at a 10% false-positive rate for the prediction of imminent delivery by a quantitative cervical length alone was 38%, yet it increased to 79% when combined with the abundance of four AF proteins (CXCL8, SNAP25, PTPN11, and MMP8). Neutrophil-mediated immunity, neutrophil activation, granulocyte activation, myeloid leukocyte activation, and myeloid leukocyte-mediated immunity were biological processes impacted by protein dysregulation in women destined to deliver within two weeks of diagnosis. The combination of AF protein abundance and quantitative cervical length improves prediction of the timing of delivery compared to cervical length alone, among women with a sonographic short cervix

Evidence for the participation of CHCHD2/MNRR1, a mitochondrial protein, in spontaneous labor at term and in preterm labor with intra-amniotic infection

Intra-amniotic inflammation (IAI), associated with either microbe (infection) or danger signals (sterile), plays a major role in the pathophysiology of preterm labor and delivery. Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 2 (CHCHD2) [also known as Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1)], a mitochondrial protein involved in oxidative phosphorylation and cell survival, is capable of sensing tissue hypoxia and inflammatory signaling. The ability to maintain an appropriate energy balance at the cellular level while adapting to environmental stress is essential for the survival of an organism. Mitochondrial dysfunction has been observed in acute systemic inflammatory conditions, such as sepsis, and is proposed to be involved in sepsis-induced multi-organ failure. The purpose of this study was to determine the amniotic fluid concentrations of CHCHD2/MNRR1 in pregnant women, women at term in labor, and those in preterm labor (PTL) with and without IAI. This cross-sectional study comprised patients allocated to the following groups: (1) mid-trimester (n = 16); (2) term in labor (n = 37); (3) term not in labor (n = 22); (4) PTL without IAI who delivered at term (n = 25); (5) PTL without IAI who delivered preterm (n = 47); and (6) PTL with IAI who delivered preterm (n = 53). Diagnosis of IAI (amniotic fluid interleukin-6 concentration ≥2.6 ng/mL) included cases associated with microbial invasion of the amniotic cavity and those of sterile nature (absence of detectable bacteria, using culture and molecular microbiology techniques). Amniotic fluid and maternal plasma CHCHD2/MNRR1 concentrations were determined with a validated and sensitive immunoassay. (1) CHCHD2/MNRR1 was detectable in all amniotic fluid samples and women at term without labor had a higher amniotic fluid CHCHD2/MNRR1 concentration than those in the mid-trimester (p = 0.003); (2) the amniotic fluid concentration of CHCHD2/MNRR1 in women at term in labor was higher than that in women at term without labor (p = 0.01); (3) women with PTL and IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those without IAI, either with preterm (p p = 0.01); (4) women with microbial-associated IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those with sterile IAI (p p  CHCHD2/MNRR1 is a physiological constituent of human amniotic fluid in normal pregnancy, and the amniotic concentration of this mitochondrial protein increases during pregnancy, labor at term, and preterm labor with intra-amniotic infection. Hence, CHCHD2/MNRR1 may be released into the amniotic cavity by dysfunctional mitochondria during microbial-associated IAI.</p

Pregnancy-specific responses to COVID-19 revealed by high-throughput proteomics of human plasma

Gomez-Lopez et al. profile the plasma proteome of pregnant and non-pregnant COVID-19 patients and controls. Shared and pregnancy-specific proteomic changes are identified in COVID-19 patients compared to controls, with the proteome accurately identifying COVID-19 patients, even when asymptomatic