Search Results (145)

Secondhand smoke (SHS), found in about 57.6% of global public areas as a widespread environmental hazard, has been associated with negative effects during pregnancy, such as preeclampsia (PE) and intrauterine growth restriction (IUGR). Our research investigated the impact of SHS on placental issues in a C57BL/6 model that simulates PE and IUGR in mice. We administered SHS to pregnant mice through a nose-only delivery method, beginning either on embryonic day 12.5 (prior to spiral artery (SA) invasion; labeled SHS-6D) or day 14.5 (following SA invasion; labeled SHS-4D), continuing up to E18.5. Control animals received only ambient air. We employed bulk RNA sequencing to assess and describe changes in placental gene expression patterns. For the SHS-4D group, which mimicked IUGR, compared to untreated controls, results showed elevated levels of inflammation-related genes (IL11RA, CHI3L1) alongside likely interference in pathways for antibody-triggered complement activation, marked by reduced expression of C1QA, C1QB, and C1QC. Immune profiling also indicated decreased macrophage activity in the placentas of the SHS-4D group relative to those from normal pregnancies at term. In contrast, the SHS-6D versus control analysis revealed lowered expression of collagen-related genes (COL1A1, COL4A5, COL4A6, COL17A1). Additionally, SHS-6D exhibited higher levels of genes associated with cell-based lysis processes compared to SHS-4D. An evaluation of the existing literature revealed that nearly every differentially expressed gene (DEG) identified in our work has been reported in studies associated with SHS exposure. Yet, few of these DEGs are discussed alongside PE or IUGR in prior reports, highlighting gaps in knowledge about how SHS triggers these conditions. Overall, we determined that the timing of SHS exposure in pregnant mice results in unique patterns of gene regulation and involvement in biological pathways. Full article

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are major pregnancy complications that are linked to placental dysfunction and environmental stimulation such as the use of electronic cigarettes (eCig). This study investigates the molecular impacts of timed eCig exposure in a C57BL/6 mouse model of PE and IUGR using bulk RNA-sequencing of placental tissues. Pregnant mice were exposed to eCig vapor via nose-only system starting at embryonic day 12.5 (eCig-6d, before spiral artery (SA) invasion) or 14.5 (eCig-4d, after SA invasion) until E18.5 (necropsy), with healthy controls exposed to room air (n = 6/group). The eCig-4d group developed PE, whereas the eCig-6d group developed both PE and IUGR. RNA-seq analysis revealed 429 differentially expressed genes (DEGs) in eCig-4d (IUGR-like) group and 64 DEGs in eCig-6d (PE + IUGR-like) group compared to controls. Pathway and gene network analyses indicated that eCig-4d exposure activated NF-κB–driven inflammation, suppressed ECM organization and collagen biosynthesis, and downregulated vasoactive genes/mitochondrial-associated genes (NOS1/2), accompanied by impaired complement initiation and reduced both macrophage and monocyte signals. Similarly, eCig-6d exposure led to downregulation of complement-associated genes and granule-related components, possibly implicating weakened neutrophil responsiveness and compromised inflammatory resolution at the maternal–fetal interface. Our findings align with prior studies on physiological dysfunctions in PE and IUGR, while also providing novel insights into the temporally specific cellular responses induced by eCig exposure. Full article

Background/Objectives: Overweight and obesity during pregnancy are metabolic risk factors that may compromise offspring brain development. The first 1000 days of life represent a critical window in which neurodevelopmental trajectories are shaped by intrauterine and early-life exposures. The 6- and 12-month milestones are key checkpoints where deviations may emerge, and interventions are most effective. This study evaluated the association between maternal pregestational weight status and infant neurodevelopment at 6 and 12 months of age. Methods: Mother and infant pairs from the OBESO perinatal cohort in Mexico City were included. Women in the first trimester of pregnancy were classified as normal weight and overweight/obesity according to their pregestational body mass index (pBMI), calculated from self-reported pre-pregnancy weight. Infant neurodevelopment was assessed at 6 and 12 months using the Bayley Scales of Infant Development III, Third Edition (BSID-III). Descriptive, bivariate and multiple linear regression analyses with mixed effects correction were conducted. Results: Among 97 mother–infant pairs, infants of mothers with overweight/obesity had lower language and socio-emotional scores at 12 months. Higher maternal pBMI was correlated with lower motor scores at 6 and 12 months, and with lower language scores at 12 months. Longitudinal analysis showed that maternal overweight/obesity was associated with a significant decline in language development from 6 to 12 months. (p = 0.002). Conclusions: Maternal pregestational overweight or obesity may negatively influence early neurodevelopment, particularly affecting language and cognitive domains during the first year of life. These early deficits could reflect alterations in intrauterine programming associated with maternal metabolic status. Full article

Background: Abiogenesis is hypothesized to have occurred in the aquatic environments of the early Earth approximately 3.8–4.0 billion years ago, in oceans containing high concentrations of ions (Na⁺ ≈ 470 mmol/L, Cl⁻ ≈ 545 mmol/L, Mg²⁺ ≈ 51–53 mmol/L, Ca²⁺ ≈ 10 mmol/L, K⁺ ≈ 10 mmol/L, SO₄²⁻ ≈ 28–54 mmol/L, HCO₃⁻ ≈ 2.3 mmol/L). Primitive membranes evolved ion-regulatory mechanisms to sustain electrochemical gradients, enabling metabolic activity. Objectives: This review compares the composition of amniotic fluid (AF) to seawater, framing AF as a “biological ocean” for the fetus, and evaluates the impact of micro- and nanoplastics (MNPs) on this protected milieu. Methods: We synthesized data from published studies on concentrations of and ions and other important substances in AF during pregnancy and compared them with marine values. Reports of MNPs detected in placenta, AF, and human organs were systematically reviewed. Results: AF exhibits high ionic similarity to seawater, although the absolute concentrations of ions are lower, reflecting evolutionary conservation. Recent analytical studies identified MNPs in samples of human placenta (4–10 particles per 1 g of tissue), meconium (median 3–5 particles per g), and AF (detectable in >60% of tested samples). Co-exposure to heavy metals, persistent organic pollutants, and endocrine disruptors were reported in 20–40% of maternal–fetal samples. Conclusions: The analogy between oceans and AF underscores a conserved evolutionary continuum. However, the infiltration of MNPs into intrauterine environments is a novel toxicological challenge with potential implications for neurodevelopment, immune programming, and epigenetic regulation. Within the One Health framework, protecting AF from anthropogenic contaminants is as critical as safeguarding marine ecosystems. Full article

Introduction: Little is known about the effects of intrauterine exposure to SARS-CoV-2, especially on growth and neurodevelopment in children. Objective: We wished to verify the effect of intrauterine exposure to SARS-CoV-2 on neurological development in children. Methods: Infants born to mothers presenting with SARS-CoV-2 infection during pregnancy were enrolled in a prospective descriptive–analytical study involving outpatient appointments performed 6 and 12 months after birth. Their neurological development was assessed using the Bayley-III Scale, using a score of >85 as the cutoff threshold for identifying developmental delay. Differences between groups were assessed through an ANOVA, using Bonferroni correction for multiple comparisons. Regression models were employed to examine the associations between the Bayley-III scores and maternal features. Results: Two hundred and sixty-nine infants were evaluated, most of whom were born full-term and with birth weights appropriate for gestational age at delivery. Developmental delays were observed in 26% of the infants in at least one of the Bayley-III domains. The language domain was particularly affected, with impairments observed in children exposed to SARS-CoV-2 closer to the time of delivery. These findings were statistically significant (p < 0.05). Conclusions: Infants born to mothers presenting with SARS-CoV-2 infection during pregnancy presented developmental delays at 6 and 12 months, particularly in the language domain. These findings reinforce the relevance of long-term clinical follow-ups of newborns exposed to SARS-CoV-2 infection during pregnancy. Full article

Pelvic inflammatory disease (PID) encompasses a broad range of infection-induced inflammatory disorders of the female upper genital tract, commonly caused by ascending sexually transmitted infections. Diagnosis is often challenging because of nonspecific or absent symptoms and the overlap with other pelvic pathologies. While clinical and laboratory assessments are essential, cross-sectional imaging plays a pivotal role, especially in complicated, atypical, or equivocal cases. This review focuses on the typical and atypical imaging features of PID and highlights the crucial roles of computed tomography (CT) and magnetic resonance imaging (MRI) in its diagnostic evaluation. CT is frequently employed in emergency settings because of its widespread availability and ability to detect acute complications such as tubo-ovarian abscesses (TOA), peritonitis, or Fitz-Hugh–Curtis syndrome. However, it is limited by ionizing radiation and suboptimal soft-tissue contrast. MRI provides superior tissue characterization and multiplanar imaging without radiation exposure. When combined with diffusion-weighted imaging (DWI), MRI achieves high diagnostic accuracy, particularly in differentiating PID from other entities such as endometriosis, adnexal tumors, and gastrointestinal or urinary tract diseases. This review also addresses PID in specific clinical contexts, including post-partum infection, post-assisted reproductive technologies (ART), intrauterine device (IUD) use, and chronic or recurrent forms. A comprehensive, multimodal imaging approach integrated with clinical findings is essential for timely diagnosis, effective treatment, and prevention of severe reproductive sequelae. 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

The intrauterine environment is increasingly recognised as a critical period for the emergence of mental health vulnerabilities. This review explores how adverse maternal exposures, such as psychological stress, infection, malnutrition, and environmental toxins, can disrupt foetal neurodevelopment via epigenetic mechanisms, contributing to the risk of psychiatric and neurodevelopmental disorders. Focusing primarily on human studies, we synthesise evidence on DNA methylation, histone modifications, and non-coding RNAs as key pathways through which the intrauterine environment influences gene regulation in the developing brain. We examine how timing of exposure, foetal sex, and gene–environment interactions modulate these effects, with particular attention to disorders such as schizophrenia, autism spectrum disorder, depression, and anxiety. The placenta emerges as a central mediator, both reflecting and shaping epigenetic changes in response to maternal signals. We also discuss the reversibility of epigenetic marks and highlight emerging interventions, including nutritional supplementation and maternal mental health support, that may buffer or reverse prenatal epigenetic programming. Methodological challenges are addressed, including tissue specificity and causal inference, and future directions are proposed toward integrating epigenetic biomarkers into early risk assessment and precision mental health and psychiatry. This review emphasises the importance of the prenatal period as a window of vulnerability and opportunity for shaping lifelong mental health. Full article

According to research, intrauterine exposure to non-pathogenic maternal microorganisms during pregnancy is influenced by the mother’s nutritional, metabolic, and immunological status. This study investigates the association between maternal gut microbiota composition, fetal development, and neonatal microbiota, with the aim of exploring their interconnected health dynamics. A cohort-based correlational study was conducted involving 114 women (≥18 years old, ≤12 weeks of gestation) attending prenatal consultations at the ISSSTE General Hospital in Pachuca de Soto, Hidalgo, México. Data were collected at four stages: before 11 weeks, at 11–14 weeks, at 20–24 weeks, and at 31 weeks of pregnancy. Assessments included anthropometric measurements, biochemical markers, and intestinal microbiota analysis. The Firmicutes/Bacteroidetes (F/B) ratio positively correlated with venous duct flow and expected weight for gestational week (r = 0.02272, p = 0.0323; r = 0.2344, p = 0.0271). Bacteroidetes showed a positive correlation with birth weight (r = 0.2876, p = 0.0063), birth height (r = 0.5889, p < 0.001), and head circumference (r = 0.2163, p = 0.0418). Correlation analysis revealed significant relationships between maternal and neonatal microbiota, particularly for Bacteroidetes and Firmicutes. The findings suggest that maternal gut microbiota significantly influences fetal growth and neonatal microbiota composition. These insights underscore the importance of maternal health during pregnancy. Full article

Antenatal inflammation/infection is a major cause of neonatal apnoea and hypoventilation. Prostaglandin E2 (PGE₂) is a key inflammatory mediator associated with depression of fetal and neonatal breathing. We aimed to determine whether antenatal ibuprofen, a cyclooxygenase inhibitor that reduces synthesis of PGE₂, restores fetal breathing movements (FBM) in late-gestation fetal sheep exposed to systemic lipopolysaccharide (LPS). Fetal sheep (125 days gestation, d; term ~148 d) were instrumentally monitored for continuous measurement of FBM and physiological parameters. At 130 d fetuses were randomly allocated between groups receiving i.v. saline (CTL_SAL, n = 9), escalating doses of LPS (i.v.) over 3 days (LPS_SAL, n = 8), or ibuprofen one hour after each LPS dose (LPS_IBU, n = 8). Regular plasma samples were collected for PGE₂ assessment. At 135 d, cerebrospinal fluid and brainstem tissue were collected at autopsy for assessments of PGE₂ expression, and immunohistochemical quantification of astrocytes and microglia within key brainstem respiratory centres was performed to assess inflammation. LPS exposure increased PGE₂ levels in plasma, cerebrospinal fluid and the RTN/pFRG (p < 0.05) and decreased the incidence, amplitude and amount of the accentuated (>5 mmHg) FBMs. Ibuprofen reduced plasma and RTN/pFRG PGE₂ expression (p < 0.01 and p = 0.031, respectively) but did not restore FBMs. Astrocyte and microglial density increased in the RTN/pFRG, NTS and raphe nucleus in LPS_IBU fetuses, compared to LPS_SAL (p < 0.05). Antenatal ibuprofen treatment did not restore depressed FBM, despite reducing the circulating and brainstem PGE₂ levels in LPS-exposed fetal sheep. Other inflammatory pathways or more specific targeting of PGE₂ may be more effective in preventing apnoea caused by exposure to intrauterine infection/inflammation. Full article

Background: Cervical cancer treatment with advanced radiotherapy techniques benefits from image guidance, particularly when anatomical changes occur during therapy. This case emphasizes the need for adaptive radiotherapy when target volume shifts significantly. Methods: A 70-year-old woman with International Federation of Gynecology and Obstetrics (FIGO) IIIC2 9th edition cervical squamous cell carcinoma presented with a distended uterine cavity due to fluid accumulation. She underwent definitive chemoradiotherapy using Volumetric Modulated Arc Therapy (VMAT) and weekly cisplatin. Results: Daily Cone Beam Computed Tomography (CBCT) imaging revealed progressive uterine shrinkage as intrauterine fluid drained, significantly altering target volume and organ-at-risk (OAR) positioning. These changes necessitated two re-planning CT scans during external beam radiotherapy to maintain accurate dosing and avoid OAR toxicity. The patient completed treatment, including image-guided brachytherapy, without complications. Adaptive planning ensured adequate tumor coverage and minimized normal tissue exposure. Conclusions: This case highlights the critical role of daily CBCT in detecting anatomical changes during radiotherapy. Adaptive re-planning, though rarely required more than once, was essential here to preserve treatment accuracy. CBCT should be considered a standard verification tool in cervical cancer radiotherapy, particularly in cases involving intrauterine fluid. Full article

Cleft palate is a common birth defect worldwide and is caused by both genetic and environmental factors. Intrauterine drug exposure is one of the environmental factors that can induce cleft palate. Mycophenolate mofetil (MPM) is an immunosuppressant drug with teratogenic effects, including cleft palate. However, the research on MPM-induced cleft palate remains limited. Sasa veitchii extract (SE), a medical plant extract, is commercially available in Asia and has been reported to show effectiveness against oral diseases. The purpose of the present study is to evaluate whether SE protects against MPM-induced immunosuppression in human embryonic palatal mesenchymal (HEPM) cells. Cell viability and G1 phase-related cell cycle markers were assessed by co-treatment with MPM and SE. Furthermore, we quantified cleft palate-associated miRNA levels and the expression of its downstream genes. MPM treatment reduced cell viability in a concentration-dependent manner. Co-treatment with SE alleviated MPM-induced inhibition of HEPM cell proliferation. Additionally, SE reduced MPM-induced miR-4680-3p upregulation and the downregulation of its downstream genes (ERBB2 and JADE1). These results suggest that SE alleviated MPM-induced cell proliferation inhibition through modulating miR-4680-3p expression. Full article

Emerging research suggests that the intrauterine environment plays a critical role in predisposing individuals to metabolic syndrome (MetS), a constellation of conditions that heightens the risk for heart disease, stroke, and diabetes. Traditionally linked to lifestyle, the risk for MetS is now understood to be also influenced by fetal exposures. The environment in which a child lives offers abundant potential sources that can contribute to an increased risk of developing various diseases, and in some cases, these factors can be avoided. This review integrates findings from both epidemiological and experimental research to underscore the impact of prenatal factors, including maternal nutrition, obesity, gestational diabetes (GDM), and birth size, on the subsequent development of metabolic derangements in offspring, particularly during puberty. The progression of genetic and epigenetic studies has enlightened the pathophysiology of these conditions starting in the intrauterine period and continuing into early life. By examining data and studies, this article elucidates the prenatal influences and underlying mechanisms that contribute to the pathogenesis of MetS. The updated understanding of the link between the intrauterine environment and future health comorbidities will draw attention to intrauterine care and maternal health and contribute to the prevention of serious diseases in adulthood. Full article

Intrauterine growth restriction (IUGR) affects 5–10% of pregnancies with placental hypoxia, playing a key role as a common pathophysiological pathway of different etiologies. Despite the high metabolic rate of the placenta and its “gatekeeper” role in protecting the fetus from hypoxia, the response of placental mitochondria to hypoxic stress is not well understood. This study tested the hypothesis that transient exposure to hypoxia leads to a loss of placental mitochondria and affects their function. Human villous trophoblastic (JEG-3) cells were cultured under normoxic and hypoxic conditions for 24 h. Mitochondrial content was determined by flow cytometry before and after hypoxic exposure and after 24 h of normoxic recovery. Parameters of oxidative phosphorylation were assessed using a respirometric analyzer before hypoxic exposure and after normoxic recovery. Mitochondrial content decreased significantly from 88.5% to 26.7% during hypoxic incubation. Although it had increased to 84.2% after 24 h of normoxic recovery, oxidative phosphorylation parameters were still significantly suppressed to 1/2 to 1/3 of the pre-incubation levels. The results underscore the ability of placental cells to adapt mitochondrial content to O₂ supply. Despite rapid recovery under normoxia, respiratory function remains suppressed, which may result in persistent impairment of adenosine triphosphate (ATP)-dependent synthetic and transport functions. Full article

Trophoblast fusion into the multinucleated syncytiotrophoblast (SCT) appears as an inescapable feature of placentation in mammals and other viviparous species. The trophoblast cells underlying the syncytium are considered a reservoir for the restoration of the aging peripheric structure. The transition from trophoblasts to SCTs has to be tightly regulated, and could be altered by genetic anomalies or environmental exposure. The resulting defective placental function could be one of the causes of the major placental diseases, such as preeclampsia (PE) and Intra-Uterine Growth Restriction (IUGR). This review attempts to take stock of the current knowledge about fusion mechanisms and their deregulations. Full article