Search Results (2,519)

With estrus confined to three winter months, early pregnancy detection is essential for reproductive management in farmed sika deer. However, the development of reliable non-invasive early pregnancy detection techniques has been hindered by limited understanding of their reproductive physiology. To identify pregnancy-specific biomarkers in sika deer, we performed RNA-sequencing (RNA-Seq) on maternal peripheral blood collected on days 0, 7, 15, and 20 after artificial insemination. Using time-series clustering analysis and weighted gene co-expression network analysis (WGCNA), we identified key genes and pathways at each stage. Notably, maternal-fetal recognition-related interferon-stimulated genes (ISGs; IFNAR1/2, STAT1/2, MX1/2, and RSAD2), anti-apoptotic and immune-regulatory genes (BCL2, XIAP, and IL10), and cysteine metabolism genes (CTH, CBS, GCLC, and GCLM) were upregulated by day 7, suggesting their role in supporting corpus luteum development through immune regulation and redox homeostasis. By days 15–20, upregulated genes were enriched in pathways related to mitochondrial function, cell adhesion, and cell cycle regulation, indicating their involvement in embryo adhesion and syndesmochorial placentation. In conclusion, this study demonstrates that ISGs, immune-regulatory genes and cysteine metabolism genes are detectable as early as day 7 post-insemination, highlighting their promise as early pregnancy biomarkers and providing a molecular basis for non-invasive diagnostic development in sika deer. Full article

Background: Extremely low birth weight (ELBW) and extremely low gestational age (ELGA) remain major challenges in neonatology, contributing to neonatal morbidity and mortality. This study aims to examine the association between functional variants of MTHFR and PON1, genes involved in homocysteine metabolism, and the risk of ELGA, ELBW, and other complications of prematurity. A meta-analysis was also conducted to integrate literature data with the results of this study. Methods: The study included 377 premature infants, 164 mothers, and a population-based sample of 404 individuals. Genotyping was performed using TaqMan assays. Results: The fetal, but not maternal, MTHFR rs1801133 genotype was associated with ELBW (OR = 1.65; 95% CI: 1.09–2.51; p = 0.017, dominant model), bronchopulmonary dysplasia (p = 0.028), patent ductus arteriosus (p = 0.017), and neonatal mortality. The meta-analysis, which included five studies spanning 1156 cases and 1124 controls, confirmed the association between the neonatal MTHFR genotype and low birth weight (LBW), demonstrating an association of the rs1801133T allele with LBW in the TT homozygote model (vs. CT: OR = 1.41; 95% CI: 1.08–1.80; p = 0.0097). Subgroup analyses indicated that the rs1801133T allele is a protective factor against LBW in more developed countries, such as Canada and the UK (dominant model), whereas in other countries, such as China, Turkey, and Poland, it is a risk factor for LBW (recessive model). No association with PON1 variants with ELBW or ELGA was found. Conclusions: This study provides the first global evidence confirming that the neonatal MTHFR genotype contributes to LBW, underscoring the population-specific effects of this genetic variant. Full article

Objective: Multifetal gestations are linked to an increased risk of pregnancy-related hypertensive disorders and other adverse outcomes. The probability positively correlates with the number of fetuses. Therefore, the objective of the study was to assess the use of various maternal and pregnancy-related characteristics for the prediction of adverse pregnancy outcomes in triplet pregnancies, dependent on different possible predictive factors such as maternal age, BMI, assisted reproductive technology (ART), parity, uterine artery Doppler (UtA-PI) measured and chorionicity. Methods: This was a screening study in 99 triplet pregnancies to evaluate the risk for adverse pregnancy outcomes for PE, hypertension, fetal growth restriction (FGR), intrauterine fetal death (IUFD), small for gestational age (SGA) and preterm birth below 32 + 0 gestational weeks, dependent on different possible predictive factors. Logistic regression analysis was performed. Results: 99 triplet pregnancies were included. Additionally, 58 women (58.6%) developed adverse pregnancy outcomes: FGR 16.2%, SGA (3.0%). Gestational hypertension was observed in 16 pregnancies (16.2%), and preeclampsia was diagnosed in 11 cases (11.1%). Furthermore, 6 pregnancies (6.2%) were complicated by IUFD, and 36 pregnancies (36.4%) resulted in preterm birth before 32 + 0 weeks of gestation. Conclusions: Hypertension and PE are common maternal complications in triplet pregnancies. While higher maternal age is a clear predictor of hypertension and PE, a model based on maternal and pregnancy characteristics did not provide sufficient predictive accuracy. Full article

Background: The human fetal adrenal gland is a unique endocrine organ with distinct morphology and functional dynamics, which is significantly different from the postnatal adrenal. Its rapid growth and vital steroidogenic role during gestation have positioned it as a key regulator of fetal development and pregnancy maintenance. Objectives: To provide a comprehensive overview of the morphogenesis, function, regulatory mechanisms, and clinical implications of the human fetal adrenal gland, highlighting recent advances in understanding its development and its role in prenatal and postnatal health outcomes. Methods: A systematic review was conducted, including original research articles focused on human fetuses or validated animal models, examining the genetic, molecular, and hormonal mechanisms underlying adrenal development and function. Studies were excluded if they were editorials, case reports, focused on adult adrenal physiology, had small sample sizes, or were non-English publications. Study quality was evaluated using PRISMA guidelines. Results: The fetal adrenal gland develops from both mesodermal and ectodermal origins, forming three primary zones: fetal, transitional, and definitive. Each zone has distinct functions and developmental pathways. The fetal zone, which predominates, is responsible for producing dehydroepiandrosterone sulfate, DHEA-S, which is crucial for placental estrogen synthesis. The adrenal gland undergoes rapid growth and functional maturation, regulated by ACTH, placental CRH, IGF, and the renin–angiotensin system. Disruption of adrenal function is associated with conditions such as preterm birth, adrenal hypoplasia, congenital adrenal hyperplasia, and intrauterine growth restriction. Emerging evidence suggests that fetal adrenal hormones may influence long-term health through fetal programming mechanisms. Conclusions: The fetal adrenal gland plays a critical and multifaceted role in fetal and placental development. This gland influences placental development via steroid precursors (DHEA-S → estrogen synthesis), while also being regulated by placental factors such as the corticotropin-releasing hormone. Understanding its complex structure–function relationships and regulatory networks is essential for predicting and managing prenatal and postnatal pathologies. Future research should focus on elucidating molecular mechanisms, improving diagnostic tools, and exploring long-term outcomes of altered fetal adrenal function. Full article

Background/Objectives: Screening for late-onset and term preeclampsia (PE) is essential, as the early identification of women at high risk enables closer monitoring and reduces adverse outcomes. The existing algorithms combining maternal factors, biophysical and biochemical markers have not been validated outside the populations in which they were originally developed. This study aimed to evaluate the predictive performance of the Fetal Medicine Foundation (FMF) third-trimester algorithm in our population and develop a novel model to improve the predictions. Methods: An observational, analytical, prospective cohort follow-up study was conducted at the Health Department of Alicante, Dr. Balmis General University Hospital, including 1580 singleton pregnancies recruited between February 2022 and November 2023 during routine third-trimester ultrasounds. Maternal clinical characteristics, blood pressure, the uterine artery pulsatility index (UtA-PI), and the sFlt-1/PlGF ratio were recorded. The FMF third-trimester algorithm was retrospectively applied at the end of pregnancy using clinical, biophysical, and biochemical data from 30 + 0 to 37 + 6 weeks via the freely accessible online calculator. The data analysis was performed using SPSS v.28 and R v.4.3.1. Results: A total of 1580 women were included, with a prevalence of late-onset PE of 2.9%. The FMF model achieved an area under the curve (AUC) of 0.87 (95% CI: 0.81–0.92), while our own model showed a superior performance, with an AUC of 0.94 (95% CI: 0.92–0.97). Conclusions: The FMF third-trimester algorithm demonstrated a good predictive performance for late-onset PE. Our newly developed model achieves an even higher predictive accuracy and offers a simplified approach to excluding the UtA-PI, which facilitates its use in routine clinical practice. Full article

Environmental stressors during the crucial period of fetal development can have a substantial impact on long-term health outcomes. A major concern is dietary exposure to endocrine-disrupting chemicals (EDCs), which can readily cross the placenta and disrupt fetal hormonal signaling and developmental programming. Examples of these chemicals include bisphenols, phthalates, pesticides, and persistent organic pollutants (POPs). Prenatal exposure to EDC has been associated with long-term effects in children, including immune disruption, metabolic dysregulation, impaired neurodevelopment, and reproductive alterations, as evidenced by human cohort studies and experimental models. Epigenetic reprogramming, direct interference with endocrine signaling, and oxidative stress (OS) are hypothesized pathways for these adverse consequences, which often combine to produce long-lasting physiological changes. This narrative review summarizes current research on maternal dietary exposure to EDCs during pregnancy, highlighting associations with adverse child health outcomes. It also discusses the growing evidence of transgenerational effects, the potential mechanisms linking prenatal exposure to long-term outcomes, and the importance of understanding the roles of timing, dosage, and chemical type. By highlighting the necessity of focused interventions to lower maternal EDC exposure and lessen threats to the health of offspring, the review concludes by discussing implications for future research, preventive measures, and public health policy. Full article

Endocrine disruptors contaminate indoor and outdoor air, water, and food. Besides modifications of the androgen/estrogen balance, endocrine disruptors can alter thyroid function, metabolic balance, immune defenses, and brain development during fetal life, childhood, and adolescence. Among the consequences of fetal exposure to endocrine disruptors, neurobehavioral disorders, particularly psychiatric disorders (for example, schizophrenia and bipolar disorder), attention deficit disorders, and mood disorders, occupy a special place. Therefore, endocrine disruptors are also neuroendocrine disruptors. This review article first summarizes the direct and transgenerational effects of endocrine disruptors. Then, data from a French national cohort of patients whose mothers were treated with synthetic hormones (estrogens and/or progestogens) during their pregnancy(ies) are used to describe the psychiatric disorders developed by children exposed in utero and the multigenerational and potentially transgenerational impacts. Full article

Background/Objectives: This article aims to investigate the multifaceted effects of alcohol on neurophysiopathological development from gestational stages through adult life and the consequent dynamic-relational challenges in individuals with Fetal Alcohol Spectrum Disorder (FASD). FASD, resulting from prenatal alcohol exposure (PAE), is characterized by a range of neurological, cognitive, behavioral, and sometimes physical impairments. This article explores how alcohol and its toxic metabolites cross the placenta, inducing direct cellular toxicity and epigenetic alterations that disrupt critical neurodevelopmental processes such as neurogenesis and brain circuit formation. Clinically, individuals with FASD exhibit diverse deficits in executive functioning, learning, memory, social skills, and sensory-motor abilities, leading to significant lifelong disabilities. A central focus is the application of the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) criteria to comprehensively frame these disabilities. The ICF’s biopsychosocial model allows for a multidimensional assessment of impairments in body functions and structures, limitations in activities, and restrictions in participation, while also considering the crucial role of environmental factors. Methods: PubMed and Semantic Scholar databases were searched for relevant papers published in English. Results: This article highlights the utility of the ICF in creating individualized functioning profiles to guide interventions and support services, addressing the limitations of traditional assessment methods. Conclusions: While the ICF framework offers a robust approach for understanding and managing FASD, further research is essential to develop and validate FASD-specific ICF-based assessment tools to enhance support and social participation for affected individuals. Full article

First-trimester placental development comprises many critical yet understudied cellular events that determine pregnancy outcomes. Improper placentation leads to a host of health issues that not only impact the fetal period but also influence later-life offspring health. Thus, an experimental paradigm for studying early placental development is necessary and has spurred the development of new in vitro models. Organoid model systems are three-dimensional structures comprising multiple differentiated cell types that originate from a progenitor population. Trophoblasts are the progenitor cells that serve as the proliferative base for the differentiation and maintenance of the placenta. Due to research constraints, experimental studies on the causal mechanisms underlying pathological pregnancies cannot readily be performed in human subjects. The nonhuman primate (NHP) offers a solution to this problem as it circumvents the limitations of human pregnancy sampling. Importantly, NHPs share many developmental features of human pregnancy, including placenta type and a similar fetal growth trajectory, making longitudinal pregnancy studies feasible and relevant. Since perturbations made in vivo can be validated in vitro, an NHP model of early pregnancy would facilitate mechanistic studies of pregnancy disorders. Herein, we describe the methodology for the establishment of a first-trimester NHP placenta trophoblast organoid model system. Full article

Caffeine is one of the most widely consumed psychoactive substances globally and is a common component of daily diets, particularly among women of reproductive age. Numerous in vitro and in vivo studies have indicated potential adverse effects of prenatal caffeine exposure, including disturbances in fetal growth, metabolic dysregulation, organ malformations, and neurodevelopmental alterations. These findings suggest that caffeine may influence multiple physiological pathways during gestation, including epigenetic modifications and metabolic programming. However, evidence from human studies remains heterogeneous and often inconclusive. Recent cohort studies and meta-analyses have reported that moderate maternal caffeine intake is not significantly associated with increased risks of gestational diabetes mellitus, gestational hypertension, or preeclampsia, although higher intake levels have been linked to anemia, preterm birth, and low birth weight in some populations. Furthermore, emerging data suggest potential associations between prenatal caffeine exposure and early neurodevelopmental outcomes, including behavioral changes, subtle structural brain differences, and alterations in offspring metabolic health and obesity risk. Despite these findings, the magnitude and clinical relevance of these effects remain uncertain, partly due to variability in caffeine sources, dosages, study designs, and reliance on self-reported intake. This review aims to synthesize current evidence on maternal caffeine consumption, its impact on pregnancy complications, fetal development, and long-term child health outcomes. By integrating experimental and clinical data, the study provides a comprehensive overview that may assist clinicians and healthcare professionals in counseling pregnant women regarding caffeine intake and potential risks. Full article

Background/Objectives: Classified as a hypertensive disorder of pregnancy, preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality. The abnormal trophoblast invasion that leads to a failed transformation of the uterine spiral arteries during placentation remains the most probable cause for preeclampsia. It is known that adiponectin acts on the placenta, playing a regulatory role in placentation processes. Therefore, the aim of this systematic review is to compile scientific evidence to evaluate the role of adiponectin as a biomarker for preeclampsia. Methods: The protocol for this systematic review was registered on the PROSPERO database (ID CRD42024542403) and follows the PRISMA 2020 guidelines. Overall, twenty-nine studies were selected from the PubMed and Scopus databases, including case–control, prospective and retrospective cohort, cross-sectional, and bidirectional Mendelian randomization studies. Results: From the articles analyzed, nine studies indicated an increase in adiponectin levels in preeclampsia, eleven reported a decrease, eight detected no significant changes, and in two studies, it was not possible to determine the glycoprotein levels. Analysis of the evidence quality revealed that moderate and low evidence levels predominate, with stronger evidence for decreased adiponectin levels. Conclusions: Promoting the advancement of scientific research is crucial, particularly exploring the association between adiponectin and other biomarkers. This approach could facilitate the development of screening and diagnostic methods, enabling the implementation of specific preventive and therapeutic strategies. Full article

Background/Objectives: Gestational weight gain (GWG) is a crucial factor influencing mother and fetal health, as high GWG is associated with adverse pregnancy outcomes and an increased long-term risk of obesity and metabolic issues in the children. In addition to controlling weight, maternal physical activity (PA) during pregnancy may influence fetal development through potential epigenetic mechanisms, including histone modifications, DNA methylation, and the production of non-coding RNA. Methods: This narrative review synthesizes evidence from randomized controlled trials (RCTs; n = 11, 3654 participants) investigating the impact of aerobic PA on GWG, while also highlighting emerging, primarily indirect findings on maternal–fetal epigenetic programming. Results: The majority of RCTs found that supervised PA interventions, especially when paired with nutritional counseling, decreased both the incidence of excessive GWG and total GWG. Enhancements in lipid metabolism, adipokine profiles, and maternal insulin sensitivity point to likely biochemical mechanisms that connect PA to epigenetic modification of fetal metabolic genes (e.g., IGF2, PGC-1α, LEP). Animal and observational studies suggest that maternal activity may influence offspring epigenetic pathways related to obesity and cardiometabolic conditions, although direct human evidence is limited. Conclusions: In addition to potentially changing gene–environment interactions throughout generations, prenatal PA is a low-cost, safe method of improving maternal and newborn health. Future RCTs ought to incorporate molecular endpoints to elucidate the epigenetic processes by which maternal exercise may provide long-term health benefits. Full article

Mast cells (MCs) belong to the cell network that regulates uterine spiral artery remodeling (uSAR), a critical vascular adaptation supporting placental development and fetal growth. Our previous in vitro study demonstrated that human MCs promote trophoblast invasion, as well as uterine vascular smooth muscle cells (uVSMCs) migration and transition to a synthetic phenotype—essential steps for a successful uSAR. Although MCs are known targets of bisphenol A (BPA), a widespread endocrine-disrupting chemical, its impact on their supportive role in uSAR is unknown. In this study, we used murine cell lines to investigate whether BPA (0.1–100 µM) affects MC-mediated promotion of cellular processes critical for uSAR. Our results showed that BPA exposure hindered MCs’ ability to promote trophoblast invasion and the switch in uVSMCs’ synthetic phenotype and migration. The highest concentrations of BPA altered the expression of genes related to MCs activation and proliferation, and of those involved in trophoblasts invasion. In contrast, low doses induced the expression of pro-inflammatory mediators in MCs without detectable effect on trophoblasts at the transcriptional level. These findings confirmed MCs as key mediators of uSAR, and identified BPA as a disruptor of their function, emphasizing its potential harmful impact on reproductive health. Full article

A systematic review of toxoplasmosis cases in patients receiving targeted immunotherapy with biologics or small molecules was performed. This systematic review searched for case reports, case series and observational studies in PubMed; last search was on 19 July 2025. The review identified 46 toxoplasmosis cases among patients receiving biologics (including CAR T-Cell Therapies) or small molecules for diverse autoimmune, oncologic and transplant conditions. These cases were reported from 18 countries, including the United States and several European countries. Most patients developed severe disease. Fifty percent (23/46) presented with cerebral toxoplasmosis, 33% (15/46) with ocular toxoplasmosis, 7% (3/46) with lymphadenopathy, 4% (2/46) with disseminated disease, 2% (1/46) with both cerebral and ocular disease, 2% (1/46) with pneumonic toxoplasmosis, and 2% (1/46) with severe fetal congenital toxoplasmosis. Among those were also four cases with fatal outcomes due to toxoplasmosis and eight cases with permanent ocular or neurological deficits. In addition, there was a case of fetal congenital toxoplasmosis that occurred despite maternal discontinuation of adalimumab five months before conception, resulting in elective pregnancy termination due to severe fetal cerebral disease. Overall, 44% (20/46) of cases were due to reactivation of chronic latent Toxoplasma infections and 39% (18/46) due to acute primary infections; 17% did not report this information. One case of disseminated acute toxoplasmosis was also identified after eating wild boar sausages, and two cases of severe acute ocular toxoplasmosis after eating undercooked venison meat, and undercooked unspecified type of meat respectively, while on small molecules or biologics. Details on the clinical presentations, management and clinical outcomes of these cases were reported. Recommendations for the management of toxoplasmosis in patients with targeted immunotherapies were also provided. Health care providers should consider toxoplasmosis in patients on biologics or small molecules who present with compatible clinical syndromes. Prompt diagnosis and treatment can be lifesaving. Full article