Search Results (241)

Telomeres are protective DNA sequences located at chromosome ends, essential to maintaining genomic stability. This narrative review examines how maternal lifestyle factors during pregnancy influence fetal telomere length (TL). Positive associations have been identified between offspring’s TL and maternal consumption of nutrients such as vitamins C and D, folate, and magnesium. Additionally, adherence to a Mediterranean diet and regular physical activity during pregnancy are correlated with increased placental TL, supporting fetal genomic integrity. Conversely, maternal dietary patterns high in carbohydrates, fats, or alcohol, as well as exposure to triclosan and sleep-disordered breathing, negatively correlate with offspring’s TL. Maternal infections may also shorten TL through heightened inflammation and oxidative stress. However, evidence regarding the impact of other lifestyle factors—including maternal stress, smoking, caffeine intake, polyunsaturated fatty acid consumption, obesity, and sleep quality—remains inconsistent. Given that shorter telomere length has been associated with cardiovascular, pulmonary, and neurodegenerative diseases, as well as certain types of cancer, these findings highlight the vital importance of maternal health during pregnancy in order to prevent potential adverse effects on the fetus. Further studies are required to elucidate the precise timing, intensity, and interplay of these influences, enabling targeted prenatal interventions to enhance offspring health outcomes. Full article

Preeclampsia (PE) is a multifactorial hypertensive disorder unique to pregnancy and a leading cause of maternal and fetal morbidity and mortality worldwide. Its pathogenesis involves placental dysfunction and an exaggerated maternal inflammatory response. Uric acid (UA), traditionally regarded as a marker of renal impairment, is increasingly recognized as an active contributor to the development of PE. Elevated UA levels are associated with oxidative stress, endothelial dysfunction, immune activation, and reduced renal clearance. Clinically, UA is measured in the second and third trimesters to assess disease severity and guide obstetric management, with higher levels correlating with early-onset PE and adverse perinatal outcomes. Its predictive accuracy improves when combined with other clinical and biochemical markers, particularly in low-resource settings. Mechanistically, UA and its monosodium urate crystals can activate the NLRP3 inflammasome, a cytosolic multiprotein complex of the innate immune system. This activation promotes the release of IL-1β and IL-18, exacerbating placental, vascular, and renal inflammation. NLRP3 inflammasome activation has been documented in placental tissues, immune cells, and kidneys of women with PE and is associated with hypertension, proteinuria, and endothelial injury. Experimental studies indicate that targeting UA metabolism or inhibiting NLRP3 activation, using agents such as allopurinol, metformin, or MCC950, can mitigate the clinical and histopathological features of PE. These findings support the dual role of UA as both a biomarker and a potential therapeutic target in the management of the disease. Full article

Prolactin (PRL) is a hormone primarily associated with lactation, but it plays various roles in both men and women. PRL belongs to the family of peptide hormones, including placental lactogen and growth hormone. Interestingly, PRL is a pleiotropic hormone affecting several physiological and pathological conditions, including fertility. Moreover, several pathophysiological roles have been associated with this hormone, including those of the immune system, autoimmune disorders, asthma, and ageing. Additionally, PRL receptors are ubiquitously expressed in tissues, including the mammary gland, gonads, liver, kidney, adrenal gland, brain, heart, lungs, pituitary gland, uterus, skeletal muscle, skin blood cells, and immune system. Therefore, in the present paper, we cover the potential role that PRL may play in asthma by promoting inflammation and modulating immune responses. The detection of its receptor in lung tissue suggests a direct role in airway smooth muscle contractility through activation of signaling pathways such as JAK2-STAT5, MAPK/ERK1/2, and PI3K/Akt, as well as influencing ionic currents that regulate cell contraction, proliferation, and survival. In this sense, this review aims to explore the potential involvement of PRL in asthma pathophysiology by examining its interactions with intracellular signaling pathways and its possible impact on airway smooth muscle contractility and immune modulation. Full article

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by venous and arterial thrombosis and obstetric complications, driven by antiphospholipid antibodies (APLAs). This review synthesizes the latest advancements and current understanding, diagnosis, and treatment of APS. APLAs, including lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-β2-glycoprotein I (aβ2-GPI), interfere with coagulation and endothelial function, as well as with placental health. APS can be primary or secondary; it is often associated with systemic autoimmune diseases like lupus. The pathogenesis of APS remains only partially understood. APLAs promote thrombosis through endothelial damage, platelet activation, and inflammatory signaling pathways. Laboratory diagnosis relies on persistent positivity for APLAs and LAC through tests like ELISA and clotting assays, following a three-step confirmation process. New integrated test systems have been introduced to improve standardization. Classification criteria have evolved, with the 2023 EULAR-ACR criteria providing a weighted, domain-based scoring system, enhancing diagnostic precision. Catastrophic APS (CAPS) is a severe, rare manifestation of APS, characterized by multi-organ failure due to rapid, widespread microthrombosis and systemic inflammation, which requires urgent anticoagulation. Seronegative APS is proposed for patients with clinical features of APS but negative standard antibody tests, possibly due to non-criteria antibodies or transient immunosuppression. Treatment primarily involves long-term anticoagulation with vitamin K antagonists; direct oral anticoagulants are generally not recommended. APS diagnosis and management remain complex due to clinical heterogeneity and laboratory challenges. Continued refinement of diagnostic tools and criteria is essential for improving outcomes in this life-threatening condition. Full article

Background: Prematurely born newborns with low birth weight constitute a group of patients who require special care from the first days of life. Prematurity and low birth weight affect about 13.4 million infants. Risk factors include placental disorders but also factors related to the mother, such as smoking, alcohol drinking, drug use, malnutrition, or certain diseases. It is imperative to educate women of reproductive age (15–49) about the basic factors influencing embryonic development, such as oral health, diet, medicine intake, and harmful habits. Even though most women are aware of the negative impact of harmful habits on the fetus, still too little attention is paid to oral health in pregnant women. Poor oral health may influence the well-being of the future mother, as well as of the child. Therefore, women of reproductive age and those who are pregnant must have adequate knowledge on this subject. The aim of this study was to assess the knowledge of Polish women of reproductive age (15–49) regarding oral health during pregnancy, including the impact of dental treatment, oral hygiene, and maternal oral conditions on pregnancy outcomes and the health of the newborn. Materials and Methods: This was a cross-sectional study of 508 women, in the reproductive age, whose age ranged from 18 to 49 years old. The surveys were conducted from April 2020 to November 2020. The questionnaire was originally developed based on the available literature and consisted of seven sections: basic information, general health and habits, pregnancy status and dental care, knowledge of treatment options during pregnancy, oral health status and its association with the risk of preterm birth, prematurity and the child’s oral health, and breastfeeding and oral development. Results: After excluding incomplete questionnaires, a total of 499 questionnaires were included in the analysis. Women participating in the study had a fairly good understanding of the impact of oral health on the fetus and the role of breastfeeding in the development of the stomatognathic system (from 50% to 70% correct answers). However, even though most respondents had completed higher education (344/68.94%), their knowledge of oral health, preterm birth, and low birth weight was very limited (including the impact of inflammation on the intrauterine development of the child or bacteria and transfer across the placenta). In these sections, the percentage of correct answers ranged from less than 20% to 50%. When analyzing knowledge by age, education, number of births, and place of residence, the highest levels of knowledge were observed among respondents with higher education, particularly those aged 27–32. Conclusions: Respondents had a fairly good understanding of the general impact of oral health during pregnancy and recognition of the importance of breastfeeding for infants. However, their knowledge about the impact of bacteria and inflammation in the mother’s oral cavity on prematurity and low birth weight was limited. Therefore, educating women of reproductive age and pregnant women on this topic is essential, as it may help reduce the adverse consequences of prematurity. Full article

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by systemic inflammation, endothelial dysfunction, and placental insufficiency. While inadequate trophoblast invasion and impaired spiral artery remodeling have long been recognized as central to its pathogenesis, emerging evidence underscores the critical roles of dysregulated iron metabolism and its crosstalk with immune responses, particularly macrophage-mediated inflammation, in driving PE development. This review systematically explores the dynamic changes in iron metabolism during pregnancy, including increased maternal iron demand, placental iron transport mechanisms, and the molecular regulation of placental iron homeostasis. We further explore the contribution of ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, to trophoblast dysfunction and pregnancy-related diseases, including PE. Macrophages, pivotal immune regulators at the maternal–fetal interface, exhibit distinct polarization states that shape tissue remodeling and immune tolerance. We outline their origin, distribution, and polarization in pregnancy, and emphasize their aberrant phenotype and function in PE. The bidirectional crosstalk between iron and macrophages is also dissected: iron shapes macrophage polarization and function, while macrophages reciprocally modulate iron homeostasis. Notably, excessive reactive oxygen species (ROS) and pro-inflammatory cytokines secreted by M1-polarized macrophages may exacerbate trophoblast ferroptosis, amplifying placental injury. Within the context of PE, we delineate how iron overload and macrophage dysfunction synergize to potentiate placental inflammation and oxidative stress. Key iron-responsive immune pathways, such as the HO-1/hepcidin axis and IL-6/TNF-α signaling, are discussed in relation to disease severity. Finally, we highlight promising therapeutic strategies targeting the iron–immune axis, encompassing three key modalities—iron chelation therapy, precision immunomodulation, and metabolic reprogramming interventions—which may offer novel avenues for PE prevention and treatment. Full article

Intrauterine growth restriction (IUGR) is a critical challenge in perinatal medicine and is associated with significant morbidity and mortality. This review explores the intricate involvement of early developmental senescence in IUGR. We highlight the dual role of cellular senescence in both normal development and pathological conditions, emphasizing the need for further research to elucidate these mechanisms and develop targeted interventions. We discuss how oxidative stress and mitochondrial dysfunction affect senescence determinants. We present emerging therapeutic strategies aimed at targeting senescence and inflammation in the placenta. We also introduce Rytvela, an interleukin-1 (IL-1) receptor modulator developed in our laboratory, which selectively attenuates pro-inflammatory signaling while preserving essential immune responses, which in turn mitigate senescence. By addressing senescence-related dysfunctions, such interventions may improve placental performance and fetal outcomes, opening up new directions for the clinical management of IUGR. Full article

Background: Histologic chorioamnionitis (HCA) is a placental inflammatory condition characterized by neutrophilic infiltration of the fetal membranes, often occurring without overt clinical signs or symptoms. Risk factors include prolonged labor, premature rupture of membranes (PROM) exceeding 12 h, nulliparity, labor dystocia, and lower socioeconomic status. Although HCA frequently presents as a subclinical condition, its early diagnosis remains challenging. Nevertheless, HCA is associated with an increased risk of maternal and neonatal morbidity, including early-onset neonatal sepsis, cerebral palsy, and long-term neurodevelopmental impairment. We report the case of a 29-year-old primigravida at 40 + 0 weeks of gestation, admitted for decreased fetal movements. Discussion: Cardiotocographic (CTG) monitoring revealed a “zigzag pattern” in the absence of maternal fever, leukocytosis, or tachycardia. Due to the CTG findings suggestive of possible fetal compromise, in addition to reduced fetal movements, an emergency cesarean section was performed. Intraoperative findings included heavily meconium-stained amniotic fluid, then the examination of the placenta confirmed acute HCA with a maternal inflammatory response, without evidence of fetal inflammatory response. Conclusion: This case highlights the crucial role of CTG abnormalities, particularly the “zigzag pattern,” as an early marker of subclinical intrauterine inflammation. Early recognition of such patterns may facilitate timely intervention and improve perinatal outcomes in cases of histologic chorioamnionitis. Full article

Preterm birth (PTB) refers to a labor before 37 gestational weeks. This is a major global contributor to neonatal morbidity and mortality. Although fetal sex is frequently treated as a confounding variable in PTB research, relatively few studies have conducted sex-stratified analyses to investigate how male and female fetuses may respond differently to various intrauterine exposures. This represents an underexplored area with important implications for understanding fetal sexual dimorphism-specific vulnerability to adverse pregnancy outcomes. Understanding the role of fetal sex differences in the pathophysiology of preterm birth (PTB) regarding processes such as inflammation, placental dysfunction, and oxidative stress is crucial. These delicate processes are tightly interrelated, but also independently contribute to pregnancy complications. Recognizing fetal sex as a biological variable for such processes is essential for improving mechanistic insight, providing refined predictive models. Full article

Preeclampsia (PE) is one of the main causes of obstetric complications and leads to both maternal and neonatal mortality. The maternal innate immune system plays an important role throughout pregnancy by providing protection against pathogens, while simultaneously inducing tolerance to a semi-allogenic developing fetus and placental development. Background/Objectives: To conduct a comparative study of immunological markers in the blood and placenta in preeclampsia. Methods: A total of 35 pregnant women were enrolled in a comparative study with preeclampsia (7) and with physiological pregnancy (28). A study of the immune status in peripheral blood and placenta was conducted with an examination of the subpopulation of lymphocytes profile and intracellular cytokines production by flow cytometry. Results: In the blood of pregnant women with PE, there was a decrease in CD14+ monocytes, as well as a significant increase of natural killers CD16+, CD56+ and activation markers HLA-DR+ and CD95+, as well as a significant rise in production of IL-10, TNF, Perforin, GM-CSF, and IGF. At the same time, in placental tissue in patients with preeclampsia, on the contrary, a significant decrease in regulatory cells CD4+, CD8+, CD14+, CD56+, CD59+, activation markers CD95+, as well as anti-inflammatory cytokine IL-10, growth factors VEGFR and IGF was detected. Conclusions: The maternal–fetal immune profile is crucial for successful fetal development and dysregulation of T-, B-, and NK cells can contribute to inflammation, oxidative stress, and the development of preeclampsia. Full article

Background and Objectives: Air pollutants have been shown to affect hypertensive disorders and placental hypoxia due to vasoconstriction, inflammation, and oxidative stress. The objective of this study was to evaluate whether high levels of maternal exposure to heavy metals during the second trimester of pregnancy are associated with an increased risk of preeclampsia and eclampsia, using national health insurance claim data from South Korea. Methods: Data on mothers and their newborns from 2016 to 2020, provided by the National Health Insurance Service, were used (n = 1,274,671). Exposure data for ambient air pollutants (PM2.5, CO, SO₂, NO₂, and O₃) and heavy metals (Pb, Cd, Cr, Cu, Mn, Fe, Ni, and As) during the second trimester of pregnancy were retrieved from the Korea Environment Corporation. Atmospheric condition data based on the mother’s registration area were matched. A logistic regression model was adjusted for maternal age, infant sex, season of conception, and household income. Results: In total, 16,920 cases of preeclampsia and 592 cases of eclampsia were identified. In the multivariate model, copper exposure remained significantly associated with an increased risk of preeclampsia (odds ratio: 1.011; 95% confidence interval: 1.001–1.023), and higher ozone exposure during pregnancy was associated with an elevated risk of eclampsia. Conclusions: Increased copper exposure during the second trimester of pregnancy was associated with a high incidence of preeclampsia. Full article

Preterm premature rupture of membranes (pPROM) is a leading cause of preterm birth (PTB) and is increasingly recognized for its association with neurodevelopmental disorders (NDDs). The disruption of fetal membrane integrity introduces potential infection and inflammation into the intrauterine environment, triggering immune responses that may affect fetal development. Placental inflammation plays a pivotal role in mediating these effects, exposing the fetus to cytokines, oxidative stress, and potential microbial insults that contribute to adverse neurodevelopmental outcomes. This review examines the current evidence of the mechanistic pathways linking pPROM-induced placental inflammation to NDDs, emphasizing the roles of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) in the inflammatory responses. We discuss how these immune activations lead to immune cell recruitment and excessive (or uncontrolled) production of inflammatory mediators, leading to an overall inflammatory imbalance that has been linked to disrupted fetal brain development in animal models. Animal models provide critical insights into how both sterile and pathogenic placental inflammation alter fetal neurodevelopment, while human studies, though limited, highlight promising biomarkers and potential therapeutic targets. This review identifies critical knowledge gaps and outlines future directions to mitigate the impact of placental inflammation on long-term infant health. Full article

The prevalence, pathogenesis, and long-term consequences of hypertension differ significantly across the sexes, and pregnancy is a special physiological stress test that can reveal a woman’s underlying cardiovascular sensitivity. In addition to being direct risks to the health of the mother and fetus, hypertensive disorders of pregnancy (HDPs), especially preeclampsia, are also reliable indicators of future hypertension and cardiovascular disease in those who are afflicted. Fetal sex has a substantial impact on maternal vascular adaptation, according to new data from placental transcriptomics and epigenetics. This may be due to variations in the expression of angiogenic, immunomodulatory, and vasoactive genes. Sex-specific patterns of placental function, inflammation, and endothelium control are specifically influenced by X-linked gene dosage, escape from X-inactivation, and sex chromosomal composition. These biological variations highlight the placenta’s potential function as a mediator and indicator of maternal cardiovascular risk, and they may help to explain why the incidence and severity of hypertensive pregnancy challenges vary depending on the fetal sex. The purpose of this review is to summarize the state of the art regarding how placental genetics and fetal sex influence maternal hypertensive risk both during and after pregnancy. Additionally, it will investigate how these findings may influence sex-specific cardiovascular screening, prediction, and prevention methods. Full article

Objective: Inflammatory arthritis (IA) has been linked to a number of adverse pregnancy outcomes (APOs), but the mechanisms linking IA-related immune dysregulation to compromised reproductive success remain poorly understood. This project will examine how IA affects pregnancy outcomes and alters the associated immune microenvironment using SKG (ZAP70^W163C) mice, a mouse model that suffers from arthritis resembling human IA. Methods: IA was induced in SKG mice on a C57BL/6J background via mannan exposure. Wild-type C57BL/6 mice served as controls. Pregnancy rates, conception time, embryo resorption rates, and immune parameters (cytokine levels and splenic/lymph node/placental immune cell subsets) were analyzed. Joint pathology was evaluated via histology (HE is staining) and anti-CCP antibody levels. Flow cytometry was used to analyze immune populations within the spleen along with the associated lymphatic nodes. Results: Synovial hyperplasia, elevated anti-CCP, and systemic inflammation were all observed in IA mice. Compared to controls, IA mice demonstrated a reduced mating success rate, prolonged conception time, decreased pregnancy rates, and increased embryo resorption. IA mice showed elevated Th1/Th17 cytokines-IFN-γ, TNF-α, and IL-17, and an expansion of pro-inflammatory immune cells, including NK cells, CD11b+ myeloid cells, neutrophils, M1 macrophages, and Tc1, in the spleen/lymph nodes. Placental immune dysregulation featured increased NKT, NK, and CD4+ cell infiltration. Conversely, anti-inflammatory subsets, such as M2 macrophages and dendritic cells, were reduced. Conclusions: IA increased APOs and skewed the immune microenvironment toward a pro-inflammatory state dominated by Th1/Th17/Tc1 responses and cytotoxic cell activation. These findings highlight immune dysregulation as a key driver of IA-associated pregnancy complications, providing mechanistic insights for therapeutic intervention. Full article

Background/Objectives: Activation of the Toll-like receptor 7 (TLR-7) plays an important role in the pathogenesis of many autoimmune diseases and viral infections. Although we have previously observed inflammation-mediated dysregulation of placental transporters, the role of TLR-7 has not been examined. Using the TLR-7 agonist, imiquimod (IMQ), we evaluated transporter expression in IMQ-treated pregnant rats and ex vivo in cultured rat placental explants. Methods: We administered 5 mg/kg (IP) of IMQ to pregnant Sprague Dawley rats on gestational day (GD) 14. The expression levels of inflammatory biomarkers and transporters were measured in maternal and fetal tissues by qRT-PCR and immunodetection methods, and effects on the placental proteome were assessed using LC/MS/MS. The involvement of TLR-7 was confirmed in rat placental explants. Results: IMQ administration resulted in Irf7 induction and increased levels of IL-6, Tnf-α, and type-I/II interferon pathways in maternal liver and placenta, which is consistent with TLR-7 activation. Proteomic profiling revealed IMQ-mediated activation of pathways involved in immune response, vesicle trafficking, and oxidative stress. Significantly decreased placental, hepatic, and renal protein expression of P-glycoprotein (PGP) was seen in the IMQ group. Likewise, TLR-7 activation using single-stranded RNA resulted in an induction of inflammatory biomarkers and downregulation of PGP in rat placental explants. Conclusions: We demonstrated that the activation of TLR-7 signaling during pregnancy reduces the expression of PGP in placenta and maternal tissues. Further studies are warranted, as decreased protein expression could result in decreased activity and altered fetal exposure to its substrates. Full article