Placental Function Research Articles

In vitro Examination of Piezo1-TRPV4 Dynamics: Implications for Placental Endothelial Function in Normal and Preeclamptic Pregnancies.

Mechanosensation is essential for endothelial cell (EC) function, which is compromised in early-onset preeclampsia (EPE), impacting offspring health. The ion channels Piezo-type mechanosensitive ion channel component 1 (Piezo1) and Transient receptor potential cation channel subfamily V member 4 (TRPV4) are co-regulated mechanosensors in ECs. Current evidence suggests that both channels could mediate aberrant placental endothelial function in EPE. Using isolated feto-placental ECs (fpECs) from early control (EC) and EPE pregnancies, we show functional co-expression of both channels and that Ca2+ influx and membrane depolarization in response to chemical channel activation is reduced in EPE fpECs. Downstream of channel activation, Piezo1 alone can induce phosphorylation of endothelial nitric oxide synthase (eNOS) in fpECs, while combined activation of Piezo1 and TRPV4 only affects eNOS phosphorylation in EPE fpECs. Additionally, combined activation reduces the barrier integrity of fpECs, also with a stronger effect on EPE fpECs. This implies altered Piezo1-TRPV4 co-regulation in EPE. Mechanistically, we suggest this to be driven by changes in the arachidonic acid metabolism in EPE fpECs as identified by RNA-Seq. Targeting of Piezo1 and TRPV4 might hold potential for EPE treatment options in the future.

P. gingivalis-Infected Macrophage Extracellular Vesicles Cause Adverse Pregnancy Outcomes.

Periodontitis is a chronic inflammatory disease triggered by oral bacterial infection, with the bacterium Porphyromonas gingivalis being a major causative agent. The association between periodontitis and various systemic diseases has been demonstrated. Recent research has also highlighted the relationship between the aggravation of maternal periodontitis and adverse pregnancy outcomes such as preterm birth and low birth weight. However, the molecular mechanisms underlying how factors from periodontitis influence pregnancy and fetal development remain unclear. Extracellular vesicles (EVs) are nano-sized spherical particles secreted into the tissue microenvironment by various types of cells. EVs have garnered interest in recent years due to their role in intercellular communication. In the present study, we investigated whether EVs derived from P. gingivalis-infected macrophages (Pg-inf EVs) reach the feto-placental unit and influence fetal development. Through a series of in vivo experiments in mice, we demonstrated that Pg-inf EVs translocated to the feto-placental unit and impaired fetal development in size and weight. Histological analysis revealed disoriented blood vessel alignment and impaired angiogenesis in the placentas of Pg-inf EV-injected groups, indicative of compromised placental function. Proteome analysis revealed a significant decrease in Vegfr1 expression in the placentas of the experimental group. Moreover, Pg-inf EVs reduced VEGFR1 expression in cultured human vascular endothelial cells, highlighting a potential molecular mechanism through which these EVs exert their effects on placental angiogenesis. This is the first study to reveal a novel pathway in which oral bacteria-infected macrophage EVs in maternal periodontitis affect pregnancy via the feto-placental unit.

The impact of gut microbiota in full-term pregnant women on immune regulation during pregnancy: A prospective, exploratory study.

This study aims to investigate the correlation between gut microbiota and both placental local immune function and the maternal systemic immune system in pregnant women. Twenty-six pregnant women were included in this study, utilizing high-throughput sequencing for gut microbiota analysis. Immune cells and cytokine levels were measured in placental tissue and peripheral venous blood. Integration of gut microbiota data with immune parameters was performed using R, and network correlation analysis was conducted with Cytoscape software. In placental tissues, gut microbiota predominantly influences B lymphocytes (CD3-CD19+/CD3-), indicating a potential bidirectional regulatory role. The impact on CD56+CD16+/CD56+CD16- and CD4+/CD8+ ratios appear minor. Notably, a significant positive correlation was observed between gut microbiota and the placental cytokine interleukin (IL)-5. In peripheral blood, gut microbiota was primarily associated with negative regulation of peripheral B lymphocytes and positive regulation of peripheral Treg cells. Minimal effects are observed on peripheral macrophages and NK cell subtypes. The most substantial impact on peripheral immune balance was reflected in the CD4+/CD8+ ratio, showing a predominant negative correlation, while the influence on the CD56+CD16+/CD56+CD16- ratio is minimal. A significant negative correlation was found between gut microbiota and peripheral cytokines IL-1 and IL-18, while the interaction with the peripheral interferon-γ/IL-4 ratio appears relatively less pronounced. The close correlation between gut microbiota and placental local immune function, as well as maternal systemic immune responses, is evident. This study contributes to a preliminary understanding of the immunomodulatory relationship of gut microbiota during pregnancy.

Maternal bisphenol A (BPA) exposure induces placental dysfunction and health risk in adult female offspring: Insights from a mouse model

Bisphenol A (BPA) is an endocrine disruptor that poses multiple risks to human health. In particular, the potential adverse effects of maternal exposure to BPA on offspring warrant further investigation. In this study, pregnant mice were exposed to BPA throughout gestation and the effects of BPA on placental function, fetal development, and health risks in adult offspring were assessed. The results showed that exposure to BPA during pregnancy led to abnormal fetal weight during the mid-to-late stages. Positron emission tomography (PET)/computed tomography (CT) and quantitative polymerase chain reaction (qPCR) were used to assess the expression of glucose transporters. The results showed that maternal BPA exposure altered glucose transport by upregulating Glut1. This alteration may significantly affect placental function and fetal development. Placental metabolomic analysis showed that BPA exposure led to downregulation of key intermediates in glucose metabolism, including UDP-d-glucose and D-glucosamine-6-phosphate. Additionally, the glycerophospholipid metabolite Dipalmitoylphosphatidylcholine (DPPC) was upregulated while CDP-choline and CDP-ethanolamine were downregulated. These disturbances in placental energy metabolism and alterations in glucose transport may be related to decreased fasting blood glucose levels and abnormal glucose tolerance in female offspring; however, these indices remained unaltered in male offspring. These findings provide preliminary insights into the potential pathological mechanisms underlying placental dysfunction and health risk caused by maternal BPA exposure in adult female offspring.

The role of DNA methylation in placental development and its implications for preeclampsia

Preeclampsia (PE) is a prevalent and multifaceted pregnancy disorder, characterized by high blood pressure, edema, proteinuria, and systemic organ dysfunction. It remains one of the leading causes of pregnancy complications, yet its exact origins and pathophysiological mechanisms are not fully understood. Currently, the only definitive treatment is delivery, often requiring preterm termination of pregnancy, which increases neonatal and maternal morbidity and mortality rates, particularly in severe cases. This highlights the urgent need for further research to elucidate its underlying mechanisms and develop targeted interventions. PE is thought to result from a combination of factors, including inflammatory cytokines, trophoblast dysfunction, and environmental influences, which may trigger epigenetic changes, particularly DNA methylation. The placenta, a vital organ for fetal and maternal exchange, plays a central role in the onset of PE. Increasing evidence suggests a strong association between DNA methylation, placental function, and the development of PE. This review focuses on the impact of DNA methylation on placental development and its contribution to PE pathophysiology. It aims to clarify the epigenetic processes essential for normal placental development and explore potential epigenetic biomarkers and therapeutic targets for PE. Such insights could lead to the development of novel preventive and therapeutic strategies for this condition.

Exploring Infant Size and Body Composition at 18 Months: An Ambidirectional Peri-Urban South African Cohort Study.

The first 1000 days of life lay the foundations for subsequent growth. This ambidirectional study, including prenatal, perinatal and postnatal factors, aimed to identify exposure variables affecting body size and composition and corresponding Z-score outcomes at age 18 months in infants born to women at low risk of adverse pregnancy outcomes in a peri-urban area of South Africa. Prenatal factors (maternal age, HIV status, anthropometry, parity, food insecurity and umbilical artery resistance index Z-score (UmA-RIAZ) as a measure of placental function, with higher UmA-RIAZ indicating poorer placental function); perinatal factors (infant sex, gestational age and birth anthropometry) and postnatal factors (infant feeding) were included as exposure variables, with infant anthropometry and body composition at 18 months as outcomes. Simple linear regression analysis was used to investigate associations between exposure variables and infant outcomes, and variables with p < 0.10 were included in the subsequent multiple regression analyses. Multiple regression analysis showed that higher UmA-RIAZ predicted lower birthweight [-0.11 kg (95% CI: -0.17, -0.04 kg)], birthweight-for-age Z-score [-0.24 (95% CI: -0.39, -0.09)] and 18-month infant length [-0.9 cm (95% CI: -1.4, -0.4 cm)] and length-for-age Z-score [-0.28 (95% CI: -0.45, -0.11)]. Maternal HIV infection predicted reduced 18-month infant length-for-age Z-score [-0.46 (95% CI: -0.83, -0.09)]. Household food insecurity predicted reduced fat-free mass-for-age Z-score at 18 months [-0.27 (95% CI: -0.51, -0.03)]. Infant anthropometry and body composition outcomes, therefore, are greatly affected by pre- and postnatal nutrition-related factors, such as placental insufficiency in utero and household food insecurity, with long-term consequences including stunting, which impact the individual, future generations and society.

NAD+ depletion is central to placental dysfunction in an inflammatory subclass of preeclampsia.

Preeclampsia (PE) is a hypertensive disorder of pregnancy and a major cause of maternal/perinatal adverse health outcomes with no effective therapeutic strategies. Our group previously identified distinct subclasses of PE, one of which exhibits heightened placental inflammation (inflammation-driven PE). In non-pregnant populations, chronic inflammation is associated with decreased levels of cellular NAD+, a vitamin B3 derivative involved in energy metabolism and mitochondrial function. Interestingly, specifically in placentas from women with inflammation-driven PE, we observed the increased activity of NAD+-consuming enzymes, decreased NAD+ content, decreased expression of mitochondrial proteins, and increased oxidative damage. HTR8 human trophoblasts likewise demonstrated increased NAD+-dependent ADP-ribosyltransferase (ART) activity, coupled with decreased mitochondrial respiration rates and invasive function under inflammatory conditions. Such adverse effects were attenuated by boosting cellular NAD+ levels with nicotinamide riboside (NR). Finally, in an LPS-induced rat model of inflammation-driven PE, NR administration (200 mg/kg/day) from gestational days 1-19 prevented maternal hypertension and fetal/placental growth restriction, improved placental mitochondrial function, and reduced inflammation and oxidative stress. This study demonstrates the critical role of NAD+ in maintaining placental function and identifies NAD+ boosting as a promising preventative strategy for PE.

Assessment of Placental Antioxidant Defense Markers in Vaccinated and Unvaccinated COVID-19 Third-Trimester Pregnancies

Background: Pregnancy has been identified as a risk factor for severe COVID-19, leading to maternal and neonatal complications. The safety and effects of the SARS-CoV-2 vaccination during pregnancy, particularly on placental function and oxidative stress (OxS), remain underexplored. We investigated the impact of vaccination on third-trimester placental antioxidant defense markers. Methods: Ninety full-term pregnant women were divided into the following groups: vaccinated (n = 27) and unvaccinated (n = 25) COVID-19-positive pregnant women; control subgroups were composed of vaccinated (n = 19) or unvaccinated (n = 19) COVID-19-negative women with a healthy term singleton pregnancy with no signs of COVID-19. Placental samples were collected after delivery. Lipid peroxidation (TBARS), gene expression of HIF-1α, and catalase (CAT), superoxide dismutase-1 (SOD1) and CAT-SOD1 enzymatic activity were measured. Results: COVID-19-positive placentae exhibited significantly higher TBARS and HIF-1α levels compared to controls, regardless of vaccination status. Vaccination significantly increased placental CAT and SOD1 expression and activity in COVID-19-positive women, suggesting enhanced antioxidant defense. Unvaccinated women showed a higher incidence of COVID-19 symptoms and lower antioxidant enzyme activity. Conclusions: SARS-CoV-2 infection induced placental OxS, which is countered by a placental adaptive antioxidant response. Vaccination during pregnancy enhances placental defense, further supporting the safety and benefits of COVID-19 vaccination in preventing complications and protecting fetal development.

Vitamin D and intrauterine growth restriction: a cross-sectional study

Vitamin D plays a critical role in maintaining bone health, regulating calcium homeostasis, and modulating immune responses. During pregnancy, it supports fetal bone mineralization and proper placental function. Deficiency in vitamin D can impair calcium absorption, disrupt placental function, and lead to adverse outcomes like intrauterine growth restriction (IUGR). Despite abundant sunlight, vitamin D deficiency is highly prevalent in countries like Indonesia. This study evaluates the relationship between maternal vitamin D levels and IUGR risk while considering additional factors like placental function and calcium metabolism. In this cross-sectional study, 60 patients, 30 with IUGR and 30 without, were included. Vitamin D levels were measured using the enzyme-linked immunosorbent assay, and statistical analysis compared the IUGR and non-IUGR groups. Baseline data [age, body mass index (BMI), placental inflammation, preeclampsia status] were analyzed using Chi-square and Mann-Whitney tests. Statistical significance was set at p&lt;0.05, using IBM SPSS 24 (IL, USA). A significant association between maternal factors and IUGR was found. Higher BMI (≥25 kg/m2) and placental inflammation were more prevalent in the IUGR group. Vitamin D deficiency was strongly linked to IUGR, with 90% of IUGR cases showing deficient levels. The IUGR group had significantly lower vitamin D levels (13.84 ng/mL versus 25.93 ng/mL), with a strong inverse correlation (r=-0.86, p=0.00). This study shows a strong link between maternal vitamin D deficiency and increased IUGR risk, emphasizing its role in placental function and fetal development.

Aberrant expression of solute carrier family transporters in placentas associated with pregnancy complications

IntroductionSolute carrier family transporters (SLCs), crucial for nutrient and trace element uptake in the placenta, play a significant role in fetal growth and development. Their dysregulation is associated with various pregnancy disorders. However, a comprehensive understanding of their role and regulation in placental function and pregnancy complications is still a largely unexplored area, making this study novel and significant. MethodsWe performed a rigorous meta-analysis of publicly available NCBI GEO microarray and RNA-Seq datasets followed by bioinformatics analysis of differentially expressed SLCs in PE and IUGR. The identified SLCs were then validated using qPCR on PE placental samples, ensuring the reliability and validity of the findings. ResultsBioinformatics analysis of preeclampsia (PE) and Intrauterine Growth restriction (IUGR) datasets revealed significant associations between specific SLC transporters with disease pathology, identified by studying differentially expressed SLCs. Subsequent validation using qPCR on placental samples confirmed considerable downregulation of SLC6A8, SLC16A10, SLC25A3, and SLC29A3, highlighting their dysregulation in the pathogenesis of PE and IUGR. DiscussionThe significant downregulation of SLC6A8, SLC16A10, SLC25A3, and SLC29A3 observed by bioinformatics analyses and validated by qPCR indicates atypical expression of these SLCs in gestational disorders. Our findings underscore the potential contribution of multiple SLC gene families to the development of placental pathologies associated with diverse pregnancy complications.

Maternal odd-chain fatty acid-rich algal oil supplementation during pregnancy improves litter characteristics of intrauterine growth restricted pregnant mice via regulating placental function

Intrauterine growth restriction (IUGR) severely impairs fetal development and offspring health. Odd-chain fatty acid (OCFA) possess beneficial biological activities in regulating insulin resistance, inflammation and oxidative stress. However, the effects of OCFA on improving IUGR through regulating placental function and maternal health remain unclear. Herein, maternal OCFA-rich algal oil supplementation improved variable coefficient of fetal weight and fetal oxidative stress in low protein diet (LPD)-induced IUGR mice model. OCFA-rich algal oil also improved placental dysfunction, placental fatty acid metabolism disorder, maternal insulin resistance, oxidative stress and intestinal injury, suggesting an improved maternal health. OCFA-rich algal oil reshaped the intestinal microbiome of dams, decreasing unclassified Bacteroidales and Parvibacter, and increasing Weissella, which positively impacted insulin resistance and intestinal injury. Overall, OCFA-rich algal oil supplementation during pregnancy ameliorated oxidative stress, insulin resistance and intestinal injury in LPD-induced IUGR pregnant mice, improved placental functions and litter characteristics, and further enhanced fetal antioxidant capacity.

Maternal infection of SARS-CoV-2 during the first and second trimesters leads to newborn telomere shortening

BackgroundInitial telomere length (TL) in newborns is the major determinant for TL in later life while TL in newborn/early-life predicts long-term health and lifespan. It is important to identify key factors that affect telomere homeostasis throughout embryonic development for precision interventions to maintain optimal TL in fetus/prenatal infants. SARS-CoV-2 has caused a widespread global pandemic of COVID-19, but it remains unclear whether maternal SARS-CoV-2 infection impairs prenatal telomere homeostasis.MethodsWe recruited 413 normally delivered newborns whose mothers were either non-infected or infected with SARS-CoV-2 during different trimesters of pregnancy (otherwise healthy). Telomere length (TL) in cord blood (CB) was assessed using qPCR. CB and maternal blood were analyzed for cytokine levels. Placental senescence was determined using senescence-associated β-galactosidase staining.ResultsControl (non-infected maternal) newborn TL was significantly longer than that from maternal infection (1.568 ± 0.340 vs 1.390 ± 0.350, P = 0.005). Such shorter TL was observed only if maternal infection of SARS-CoV-2 occurred in the first and second trimesters of pregnancy (1.261 ± 0.340 and 1.346 ± 0.353, P < 0.0001 and 0.001, respectively). There were no differences in TL between controls and infection at the third trimester (1.568 ± 0.340 vs 1.565 ± 0.329, P > 0.05). Across the first trimester, there was a positive correlation between newborn TL and gestational weeks with maternal infection, suggesting that the earlier maternal infection occurs, the worse effect is taken on fetal telomere homeostasis. Placental senescence coupled with the downregulated expression of telomerase reverse transcriptase was significantly more frequent from the maternal infection at the first trimester. There were no differences in IL-6, C reactive protein and other cytokine levels in CB and maternal serum or placentas.ConclusionsMaternal SARS-CoV-2 infection at the first and second trimesters leads to significantly shorter TL and earlier infection causes much more severe TL damage. The infection-mediated cell senescence and other histopathological abnormalities result in defective placental function through which fetal telomere homeostasis is impaired. Thus, vaccination against COVID-19 should be done in advance for women who plan pregnancy.

Placental T2* as a measure of placental function across field strength from 0.55T to 3T.

Placental MRI is increasingly implemented in clinical obstetrics and research. Functional imaging, especially T2*, has been shown to vary across gestation and in pathology. Translation into the clinical arena has been slow because of time taken to mask the region of interest and owing to differences in T2* results depending on field strength. This paper contributes methodology to remove these barriers by utilising data from 0.55, 1.5 and 3T MRI to provide a fully automated segmentation tool; determining field strength dependency of placental assessment techniques; and deriving normal ranges for T2* by gestational age but independent of field strength. T2* datasets were acquired across field strengths. Automatic quantification including fully automatic masking was achieved and tested in 270 datasets across fields. Normal curves for quantitative placental mean T2*, volume and other derived measurements were obtained in 273 fetal MRI scans and z-scores calculated. The fully automatic segmentation achieved excellent quantification results (Dice scores of 0.807 at 3T, 0.796 at 1.5T and 0.815 at 0.55T.). Similar changes were seen between placental T2* and gestational age across all three field strengths (p < 0.05). Z-scores were generated. This study provides confidence in the translatability of T2* trends across field strengths in fetal imaging.

Late-gestation maternal undernutrition induces circulatory redistribution while preserving uteroplacental function independent of fetal glycaemic state.

Programming effects of maternal undernutrition on fetal metabolic and cardiovascular systems are well elucidated, yet a detailed characterization of maternal haemodynamics is not available. This study used comprehensive cardiovascular magnetic resonance (CMR) imaging to quantify maternal haemodynamics after 29days (111-140 days) of late-gestation undernutrition (LGUN) in pregnant sheep. Control ewes received 100% of metabolizable energy requirements (MERs, n=15), whereas LGUN ewes were globally nutrient restricted to 50% MER (n=18), with a subset of fetuses undergoing continuous glucose infusion (LGUN+G, n=6/18). Ewes underwent CMR (138-140 days' gestation), and placental tissue was collected the next day. Ewes in both LGUN groups had reduced body weight and mean blood glucose concentration across gestation. Ventricular dimensions were lower in both LGUN groups. Uterine artery blood flow (QUtA) was elevated in the LGUN group compared with controls, whereas peripheral blood flow was reduced and further diminished in LGUN+G. Maternal weight change correlated with all haemodynamic parameters across all groups. Uteroplacental oxygen and glucose delivery were increased in LGUN compared to control ewes, whereas uteroplacental oxygen consumption was preserved. LGUN did not impact placental or fetal weight, and markers of brain-sparing physiology were absent. Placental expression of insulin-like growth factors (IGF-1 and IGF-2) and their receptors, glucose, fatty acid (FA) or amino acid transporters and markers of angiogenesis was not impacted. FA transporter expression was positively correlated with QUtA, and FA binding protein correlated negatively with maternal weight change. Maternal cardiovascular adaptations in response to LGUN manifest as preservation of placental growth and function, thereby preserving fetal growth. KEY POINTS: Maternal undernutrition during pregnancy alters fetal metabolic and cardiovascular physiology, but little is known about alterations in maternal haemodynamics. Late-gestation undernutrition (LGUN) and LGUN+G redirected maternal blood flow from the periphery to the uteroplacental unit, concomitantly increasing the delivery of glucose and oxygen to the uteroplacental unit. Substrate transporter expression and uteroplacental oxygen consumption were preserved in LGUN and LGUN+G, suggesting prioritization of the placenta. This study is the first to report detailed maternal haemodynamics in the setting of maternal undernutrition, where placental growth and function were maintained, ultimately preserving fetal oxygen metabolism and growth.

Oxidative Stress and Placental Pathogenesis: A Contemporary Overview of Potential Biomarkers and Emerging Therapeutics.

Oxidative stress (OS) plays a crucial role in placental pathogenesis and pregnancy-related complications. This review explores OS's impact on placental development and function, focusing on novel biomarkers for the early detection of at-risk pregnancies and emerging therapeutic strategies. We analyzed recent research on OS in placental pathophysiology, examining its sources, mechanisms, and effects. While trophoblast invasion under low-oxygen conditions and hypoxia-induced OS regulate physiological placental development, excessive OS can lead to complications like miscarriage, preeclampsia, and intrauterine growth restriction. Promising OS biomarkers, including malondialdehyde, 8-isoprostane, and the sFlt-1/PlGF ratio, show potential for the early detection of pregnancy complications. Therapeutic strategies targeting OS, such as mitochondria-targeted antioxidants, Nrf2 activators, and gasotransmitter therapies, demonstrate encouraging preclinical results. However, clinical translation remains challenging. Future research should focus on validating these biomarkers in large-scale studies and developing personalized therapies to modulate placental OS. Emerging approaches like extracellular vesicle-based therapies and nanomedicine warrant further investigation for both diagnostic and therapeutic applications in pregnancy-related complications. Integrating OS biomarkers with other molecular and cellular markers offers improved potential for the early identification of at-risk pregnancies.

Protective effect of metformin on the NG-nitro-l-arginine methyl ester (l-NAME)-induced rat models of preeclampsia

BackgroundPreeclampsia (PE) is a complex multi-organ disorder characterized by systemic inflammation, endothelial dysfunction, and vasoconstriction, which manifests as hypertension, with or without proteinuria. Effective preventive strategies for PE are currently lacking in clinical practice, leading to significant morbidity and mortality among mothers and newborns. ObjectiveThis study aims to investigate the impact of metformin (MET) on the l-NAME-induced PE rat model, focusing on the mechanisms through which MET may exert its effects. MethodsThirty pregnant Sprague-Dawley (SD) rats were randomly assigned to three groups: Control, PE, and PE + MET, on gestational day 0 (GD0). Regularly measure blood pressure and 24-h proteinuria, and collect tissue samples on GD20. Enzyme-linked immunosorbent assay (ELISA) was used to analyze inflammatory factors, endothelial function biomarkers, angiogenic factors, and apoptosis-related factors in the rat plasma. Western blot, RT-qPCR, and immunohistochemistry techniques were employed to determine the expression levels of key apoptotic proteins in placental tissue. ResultsThe study findings demonstrate that MET administration improves blood pressure and 24-h proteinuria, alleviates fetal growth restriction, ameliorate inflammation cytokines, and restores the balance of angiogenic factors and endothelial function. Moreover, MET inhibits the expression levels of critical apoptotic proteins in the plasma and placental tissue of PE-like rats. ConclusionThe results suggest that MET shows promise in alleviating symptoms associated with l-NAME-induced PE in rats, preserving endothelial function, enhancing angiogenesis, reducing inflammation, inhibiting placental apoptosis, improving placental function, and promoting fetal growth. These findings highlight MET as a potential therapeutic agent for the prevention and treatment of preeclampsia.

INFLUENCE OF UROGENEITRAL INFECTION IN PREGNANT WOMEN ON THE UTERINE – FETOPLACENTARY COMPLEX

As reported by the World Health Organization (WHO), approximately 20 % of pregnant women globally are aff ected by an infection of the lower genital tract. Urogenital infection can result in complications during the onset and progression of pregnancy, as well as the postpartum period. These complications include placental dysfunction, premature birth, low birth weight, premature rupture of the fetal membranes, and postpartum endometritis. A marker of normal placental function is α2-fertility microglobulin (AFMG), the determination of which will refl ect the presence or absence of a uterine- fetoplacental complex violation during urogenital infection in pregnant women.The aim of the study is to reveal the infl uence of urogenital infection on the dysfunction of the uterine – fetoplacental complex in pregnant women.Materials and methods. A total of 75 pregnant women were examined, divided into two groups: the main group (MG) and the comparison group (CG). The MG consisted of 55 pregnant women, of whom 35 underwent local sanitation of the urogenital infection according to the identifi ed pathogen (Subgroup A) and 20 refused this procedure (Subgroup B). The CG consisted of 20 pregnant women without urogenital infection, as determined by bacterioscopic, bacteriological, and polymerase chain reaction (PCR) examinations. All pregnant women underwent determination of AFMG in blood serum via immunoenzymatic methodology. The statistical analysis was conducted using the MedStat software (serial number MS00019). The study was performed in accordance with the provisions of the Declaration of Helsinki. The study protocol was approved by the Local Ethics Committee of PFMU for all women who participated in this study. Statistical processing was performed using the MedStat program (serial number MS00019). The work is a part of the initiative research work of the Department of Obstetrics and Gynecology No. 1 of Poltava State Medical University «Pathogenetic role of endothelial dysfunction and genetic features in pathology during pregnancy and gynecological diseases» (state registration No. 0117U005253, term of implementation 2017-2023).Research results. The results of the study demonstrated that pregnant women with a urogenital infection had a history of chronic pyelonephritis 5.5 times more frequently (p = 0.03) and salpingo- oophoritis 10.2 times more frequently (p &lt; 0.001), which may be a source of latent infection. The most prevalent infectious agents among pregnant women were: The most prevalent microorganisms were Ureaplasma urealyticum (21.4 %), Candida fungi (19.04 %), Gardnerella vaginalis (11.9 %), and Toxoplasma gondii (11.9 %). The level of AFMG in pregnant women with urogenital infection was observed to be 4.3 times lower than in pregnant women with CG (p &lt; 0.001). The remediation of an infection of the lower genital tract during pregnancy has been observed to increase AFMG production by a factor of four (p &lt; 0.001). The level of AFMG in pregnant women of CG was 2.2 times higher than in pregnant womenof Subgroup A (p &lt; 0.004).Conclusions. It was demonstrated that urogenital infection in pregnant women has a considerable impact on the dysfunction of the utero- fetoplacental complex. It was also shown that local sanitation of the lower genital tract in these women, based on the identified pathogen, has a benefi cial eff ect on the placenta’s functioning. However, this approach does not fully address the issue of protein synthesis impairment.

Maternal adiponectin restores cholinergic vasodilation in resistance vessels from adult offspring exposed to maternal obesity in utero.

Maternal obesity increases the risk of cardiovascular and metabolic disease in the offspring both during childhood and adult life. Pregnant women and mice with obesity have lower circulating levels of adiponectin (ADN) compared to lean controls. ADN is an adipokine involved in regulating energy metabolism, vascular function, and placental function. We hypothesized that offspring of obese mice have impaired resistance artery function, which can be prevented by restoration of normal circulating ADN levels in obese dams during late pregnancy. Adult female mice were fed either control or obesogenic diet and mated with control diet-fed males. Control dams received a continuous infusion of phosphate saline buffer (PBS) during late pregnancy whereas obese females received either PBS or ADN. After weaning, offspring were fed a control diet. Mesenteric arteries (MsA) were dissected from adult offspring and mounted in a wire myograph or fixed for histology. MsA responses to vasoconstrictors (phenylephrine and endothelin-1) were not different between infusion groups. However, the vasodilatory responses to acetylcholine were reduced in offspring from obese dams as compared to control-fed dams. ADN supplementation during pregnancy restored the cholinergic vasodilatory responses of resistance vessels in offspring from obese dams. These observations suggest that normalizing circulating adiponectin levels in pregnancies complicated by obesity prevents in utero programming of vascular dysfunction in the offspring.

Vicki L. Clifton: Stress, sex, and the placenta: its role in fetal and child development

Professor Vicki Clifton, PhD, GAICD, Dip Manag, Dip Counselling, FRSM, is a Mater Research Institute-University of Queensland Amplify Fellow specializing in obstetrics research through clinical trials and basic biology. With 327 publications, h-Index: 61, and over 14,000 citations, her research focuses on stress and maternal asthma during pregnancy, examining their effects on maternal health, placental function, fetal growth, and child health. She is notably recognized for her work on sex-specific placental function and stress responses influencing fetal growth and pregnancy outcomes. Professor Clifton has led her institution's asthma and pregnancy research program, establishing multi-disciplinary, end-user-engaged research programs in Australia and overseas. Her innovative research has advanced our understanding of factors affecting asthma during pregnancy, leading to new models of care and improved fetal outcomes. Her work has influenced national and international asthma management guidelines, identified sex-specific mechanisms affecting maternal-fetal health, and expanded the frontiers of existing knowledge on fetal-neonatal physiology. Through preclinical studies and clinical partnerships, she has rapidly translated findings into practice guidelines and consumer information. She currently leads the Queensland Family Cohort study, a state-wide longitudinal study linking parental and child health outcomes to biological mechanisms. A Fellow of the Royal Society of Medicine, she pioneered women's leadership as the first female President of the Endocrine Society of Australia and the first female Editor of Placenta (Elsevier). As an NHMRC Research Fellow (2000–2023), she has secured over $25 million in category 1 grants. We are privileged to have Professor Clifton share her personal and professional insights with our readers in this Genomic Press Interview.

Vitamin C supplementation improves placental function and alters placental gene expression in smokers

Maternal smoking during pregnancy (MSDP), driven by nicotine crossing the placenta, causes lifelong decreases in offspring pulmonary function and vitamin C supplementation during pregnancy prevents some of those changes. We have also shown in animal models of prenatal nicotine exposure that vitamin C supplementation during pregnancy improves placental function. In this study we examined whether vitamin C supplementation mitigates the effects of MSDP on placental structure, function, and gene expression in pregnant human smokers. Doppler ultrasound was performed in a subset of 55 pregnant smokers participating in the “Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function” (VCSIP) randomized clinical trial (NCT01723696) and in 33 pregnant nonsmokers. Doppler ultrasound measurements showed decreased umbilical vein Doppler velocity (Vmax) in placebo-treated smokers that was significantly improved in smokers randomized to vitamin C, restoring to levels comparable to nonsmokers. RNA-sequencing demonstrated that vitamin C supplementation to pregnant smokers was associated with changes in mRNA expression in genes highly relevant to vascular and cardiac development, suggesting a potential mechanism for vitamin C supplementation in pregnant smokers to improve some aspects of offspring health.