Search Results (72)

The phenotype of human placental extravillous trophoblast (EVT) at the end of pregnancy reflects both differentiation from villous cytotrophoblast (CTB) and later gestational changes, including loss of proliferative and invasive capacity. Invasion abnormalities are central to major obstetric pathologies, including placenta accreta spectrum, early onset preeclampsia, and fetal growth restriction. Characterization of the normal differentiation processes is, thus, essential for the analysis of these pathologies. Our gene expression analysis, employing purified human CTB and EVT cells, demonstrates a mechanism similar to the epithelial–mesenchymal transition (EMT), which underlies CTB–EVT differentiation. In parallel, DNA methylation profiling shows that CTB cells, already hypomethylated relative to non-trophoblast cell lineages, show further genome-wide hypomethylation in the transition to EVT. A small subgroup of genes undergoes gains of methylation (GOM), associated with differential gene expression (DE). Prominent in this GOM-DE group are genes involved in epithelial–mesenchymal plasticity (EMP). An exemplar is the transcription factor RUNX1, for which we demonstrate a functional role in regulating the migratory and invasive capacities of trophoblast cells. This analysis highlights epigenetically regulated genes acting to underpin the epithelial–mesenchymal plasticity characteristic of human trophoblast differentiation. Identification of these elements provides important information for the obstetric disorders in which these processes are dysregulated. Full article

Pregnancy orchestrates profound neurological, hormonal, and anatomical transformations in the maternal brain, preparing it for caregiving and infant bonding. Neuroimaging reveals structural changes such as gray matter reductions and white matter reorganization during pregnancy, followed by partial recovery postpartum. These adaptations are modulated by fluctuating levels of estradiol, progesterone, prolactin, and oxytocin, which coordinate neuroplasticity and behavioral readiness. At the molecular and cellular levels, pregnancy hormones drive synaptic remodeling, neurogenesis, and glial activity. Together, these changes support maternal motivation, attachment, and responsiveness, highlighting the maternal brain’s dynamic plasticity across gestation and the postpartum period. Also, pregnancy induces profound physiological changes, particularly in vascular, hormonal, and neurologic systems, to support maternal and fetal health. While these adaptations are essential, they can predispose pregnant individuals to various neurologic and ophthalmic pathologies. This review explores how pregnancy-related changes—including hypercoagulability, pituitary enlargement, hormonal fluctuations, and immunological modulation—contribute to conditions such as stroke, idiopathic intracranial hypertension, preeclampsia-associated visual disturbances, and demyelinating disorders like neuromyelitis optica spectrum disorder and multiple sclerosis. Additionally, ocular manifestations of systemic diseases like diabetic retinopathy and thyroid orbitopathy are discussed. Understanding these complex interactions is critical for prompt recognition, accurate diagnosis, and appropriate management of vision-threatening and neurologically significant complications during pregnancy. Nevertheless, many aspects of physiological and pathological changes during and after pregnancy remain unknown and warrant further investigation. Full article

The usage of plastics in life and industrial applications has led to global environmental pollution by micro- and nanoplastics (MPs/NPs). Despite their widespread occurrence in the environment, little is known about their presence in humans and the potential implications for human health, particularly maternal and fetal health during the prenatal and neonatal periods. Studies on experimental animals indicate that exposure to MPs/NPs can lead to neurological abnormalities in offspring and hemodynamic alterations in the placenta and fetal cerebral arteries. These findings underscore the need for further epidemiological studies that examine the effects of MPs/NPs on fetal health during pregnancy, a critical period for neurological development. This review summarizes the existing knowledge on the effects of prenatal exposure to MPs/NPs on fetal development and birth outcomes in humans and provides a detailed overview of the challenges encountered in contamination prevention, quality assurance and quality control in analytical procedures. It also discusses the sampling and digestion methods used for the extraction of MPs/NPs from biological samples of maternal and fetal origin, highlighting the difficulties associated with accurately quantifying these particles in complex biological matrices, identifying the gaps in current research, and suggesting recommendations to improve methodologies for assessing the risks associated with prenatal MP/NP exposure. Full article

Exposure to endocrine-disrupting chemicals (EDCs) has been linked to several pathologies in human health, especially those involving the immune system. The vast majority of studies have focused on cells and functions of the adaptive immune system with little investigation of the impact of EDCs on innate immunity. While EDC exposure remains a threat throughout the lifetime of an individual, the most detrimental effects on human health occur during critical stages of development, such as in utero. Fetal development is not only associated with growth and tissue remodeling but also with the establishment of key processes, including those of the immune system. Unfortunately, due to fetal plasticity, developmental exposure to certain EDCs, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), can affect mammalian health well into adulthood by altering fetal programming. Herein, we hypothesize that in utero exposure to TCDD induces developmental reprogramming of the innate immune system that subsequently impacts the adult response to infection. To interrogate our hypothesis, we challenged adult mice with and without a history of in utero TCDD exposure with 1 × 10⁸ CFU Pseudomonas aeruginosa via intraperitoneal injection. Results revealed a significant decrease in the number of innate leukocytes at the site of infection six hours after inoculation in toxicant-exposed mice compared to unexposed mice. The reduction in the number of phagocytes correlated with a reduction in bacterial clearance in toxicant-exposed mice. We also noted a decreased ability of peritoneal immune cells from toxicant-exposed mice to produce chemokines necessary for immune cell recruitment. Taken together, our results indicate that in utero EDC exposure impairs the innate immune response to a bacterial infection in adult offspring, particularly in males. Full article

Background: Prenatal alcohol exposure (PAE) models can cause neurodevelopmental abnormalities like those observed in fetal alcohol spectrum disorder (FASD). Previous studies link experimental PAE effects in the brain to impaired signaling through insulin/IGF and Notch pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Importantly, concurrent administration of peroxisome proliferator-activated receptor agonists or dietary soy prevented many aspects of FASD due to their insulin-sensitizing, anti-inflammatory, and antioxidant properties. Objective: To determine if dietary soy interventions during pregnancy would be sufficient to normalize central nervous system structure and function, we examined the effects of maternal gestation-limited dietary soy on cerebellar postnatal development, motor function, and critical signaling pathways. Methods: Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source. The ethanol and soy feedings were discontinued upon delivery. The offspring were subjected to rotarod motor function tests, and on postnatal day 35, they were sacrificed to harvest cerebella for histological and molecular studies. Results: Despite the postnatal cessation of alcohol exposure, chronic gestational exposure reduced brain weight, caused cerebellar hypoplasia, and impaired motor performance. Gestational dietary soy prevented the ethanol-associated reduction in brain weight and largely restored the histological integrity of the cerebellum but failed to normalize motor performance. Ethanol withdrawal abolished the impairments in insulin/IGF signaling that were previously associated with ongoing ethanol exposures, but ethanol’s inhibitory effects on Notch and Wnt signaling persisted. Soy significantly increased cerebellar expression of the insulin and IGF-1 receptors and abrogated several ethanol-associated impairments in Notch and Wnt signaling. Conclusions: Although gestation-restricted dietary soy has significant positive effects on neurodevelopment, optimum prevention of FASD’s long-term effects will likely require dietary soy intervention during the critical periods of postnatal development, even after alcohol exposures have ceased. Full article

Follicular cells represent a valuable resource for genetic research, biotechnology and cryopreservation in biobanks, particularly for the conservation of endangered species. They offer a more practical alternative to gametes, embryos and fibroblasts. Collection of these cells can be achieved through feather plucking. Feather samples were opened with a scalpel and the feather pulp was washed with PBS, cut into cubes and digested in collagenase type IV. Cultivation was carried out in DMEM culture medium with 15% fetal bovine serum, 1% penicillin/streptomycin and 0.5% amphotericin, under incubation conditions of 39.5 °C and 5% CO₂. Passages were carried out with 5% EDTA for 5 min. The culture was successful, with great cell proliferation, adherence to plastic and aggregation into cell colonies. This method was effective in obtaining feather follicle cells from wild birds, especially when collected up to 6 h after their death, and can serve as a base protocol for research with feather follicle cells aiming to create biobanks. Full article

The developmental origins of adult disease theory support the concept that undernourished fetuses are at risk of developing metabolic syndrome due to the energy-saving ‘Thrifty Phenotype’. This metabolic plasticity represents an evolutionary adaptation that allows individuals to resist the intense pressure caused by cyclically recurring periods of nutritional deprivation. A comprehensive review was conducted following an extensive literature search in the PubMed/Medline and EMBASE databases concerning reports on fetal/intrauterine growth restriction and its metabolic-related long-term outcomes. We only included articles written in English that were published before 1 July 2024. There are several underlying mechanisms and metabolic and endocrine adjustments shaped by the perinatal environment, and they all contribute to progression towards adult disease. From in utero malnutrition or other insults during the fetal period to fetal programing and postnatal catch-up growth, it is difficult to identify the exact moment when this adaptative phenomenon meant to assure fetal survival and to set children on their own physiological growth curves lose its beneficial effect, establishing the trajectory to obesity, insulin resistance, and other hallmarks of metabolic syndrome. With clinical correspondence to an altered body mass, composition, and eating behaviors, it is evident that the metabolic complications linked to FGR are intricate and arise from disturbances in several pathways and organs, but the underlying processes responsible for the long-term consequences are just starting to be understood. The lack of continuity in perinatal-to-pediatric FGR research sets the challenge of exploring new directions in future scientific opportunities. These will hopefully represent a cornerstone in the management of FGR-related metabolic disorders in children, preventing these disorders from evolving into adult disease. Full article

During pregnancy, reproductive hormonal changes could affect the mental health of women, such as depression and anxiety. Previous studies have shown that exposure to endocrine disrupting chemicals (EDCs) is significantly associated with mental health symptoms; however, the results were inconsistent. We aimed to examine the association between 24 endocrine-disrupting chemicals (EDCs) in maternal urine and perinatal depression and their association with dietary and lifestyle factors. Participants were recruited from the “No Environmental Hazards for Mother–Child” cohort in Korea. Structured questionnaires asking dietary and lifestyle factors and evaluation of depressive symptoms were administered during antepartum (14 weeks of gestation) and postpartum (within four weeks after birth) periods. Urine samples were collected from 242 and 119 women during antepartum and postpartum periods, respectively. To assess perinatal depression, we used the Center for Epidemiological Studies-Depression Scale and the Edinburgh Postnatal Depression Scale. Antepartum depression and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) (1.50, 1.01–2.23) and 1-hydroxypyrene (1-OHP) (0.05, 0–0.89) showed significant positive association. Additionally, postpartum depression showed significant associations with mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) (2.78, 1.00–7.70), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (2.79, 1.04–7.46), 2-hydroxynaphthalene (2-NAP) (7.22, 1.43–36.59), and 2-hydroxyfluorene (2-FLU) (<0.01, 0–0.004). Some dietary factors (consumption of fish, fermented foods, cup noodles, and popcorn) and consumer product factors (use of skin care, makeup, perfume, antibiotics, sunscreen, nail polish, new furniture, plastic tableware, detergent, polish, paint, and pesticide) were associated with the concentration level of chemicals. We found that exposure to several EDCs during pregnancy and the postpartum period was associated with perinatal depression and dietary–lifestyle factors. Women in childbirth need to actively seek out information about exposure to EDCs and make efforts to avoid them for their own and fetal health. Full article

Dibutyl phthalate (DBP) is a low-molecular-weight phthalate commonly found in personal care products, such as perfumes, aftershaves, and nail care items, as well as in children’s toys, pharmaceuticals, and food products. It is used to improve flexibility, make polymer products soft and malleable, and as solvents and stabilizers in personal care products. Pregnancy represents a critical period during which both the mother and the developing embryo can be significantly impacted by exposure to endocrine disruptors. This article aims to elucidate the effects of prenatal exposure to DBP on the health and development of offspring, particularly on the reproductive, neurological, metabolic, renal, and digestive systems. Extensive research has examined the effects of DBP on the male reproductive system, where exposure is linked to decreased testosterone levels, reduced anogenital distance, and male infertility. In terms of the female reproductive system, DBP has been shown to elevate serum estradiol and progesterone levels, potentially compromising egg quality. Furthermore, exposure to this phthalate adversely affects neurodevelopment and is associated with obesity, metabolic disorders, and conditions such as hypospadias. These findings highlight how urgently stronger laws prohibiting the use of phthalates during pregnancy are needed to lower the risks to the fetus’s health and the child’s development. Full article

Adipose-derived stem cells (ADSCs) hold promise for tendon repair, even if their tenogenic plasticity and underlying mechanisms remain only partially understood, particularly in cells derived from the ovine animal model. This study aimed to characterize oADSCs during in vitro expansion to validate their phenotypic properties pre-transplantation. Moreover, their tenogenic potential was assessed using two in vitro-validated approaches: (1) teno-inductive conditioned media (CM) derived from a co-culture between ovine amniotic stem cells and fetal tendon explants, and (2) short- (48 h) and long-term (14 days) seeding on highly aligned PLGA (ha-PLGA) electrospun scaffold. Our findings indicate that oADSCs can be expanded without senescence and can maintain the expression of stemness (Sox2, Oct4, Nanog) and mesenchymal (CD29, CD166, CD44, CD90) markers while remaining negative for hematopoietic (CD31, CD45) and MHC-II antigens. Of note, oADSCs’ tendon differentiation potential greatly depended on the in vitro strategy. oADSCs exposed to CM significantly upregulated tendon-related genes (COL1, TNMD, THBS4) but failed to accumulate TNMD protein at 14 days of culture. Conversely, oADSCs seeded on ha-PLGA fleeces quickly upregulated the tendon-related genes (48 h) and in 14 days accumulated high levels of the TNMD protein into the cytoplasm of ADSCs, displaying a tenocyte-like morphology. This mechano-sensing cellular response involved a complete SOX9 downregulation accompanied by YAP activation, highlighting the efficacy of biophysical stimuli in promoting tenogenic differentiation. These findings underscore oADSCs’ long-term self-renewal and tendon differentiative potential, thus opening their use in a preclinical setting to develop innovative stem cell-based and tissue engineering protocols for tendon regeneration, applied to the veterinary field. Full article

Gestational diet has a long-dated effect not only on the disease risk in offspring but also on the occurrence of future neurological diseases. During ontogeny, changes in the epigenetic state that shape morphological and functional differentiation of several brain areas can affect embryonic fetal development. Many epigenetic mechanisms such as DNA methylation and hydroxymethylation, histone modifications, chromatin remodeling, and non-coding RNAs control brain gene expression, both in the course of neurodevelopment and in adult brain cognitive functions. Epigenetic alterations have been linked to neuro-evolutionary disorders with intellectual disability, plasticity, and memory and synaptic learning disorders. Epigenetic processes act specifically, affecting different regions based on the accessibility of chromatin and cell-specific states, facilitating the establishment of lost balance. Recent insights have underscored the interplay between epigenetic enzymes active during embryonic development and the presence of bioactive compounds, such as vitamins and polyphenols. The fruit of Manilkara zapota contains a rich array of these bioactive compounds, which are renowned for their beneficial properties for health. In this review, we delve into the action of each bioactive micronutrient found in Manilkara zapota, elucidating their roles in those epigenetic mechanisms crucial for neuronal development and programming. Through a comprehensive understanding of these interactions, we aim to shed light on potential avenues for harnessing dietary interventions to promote optimal neurodevelopment and mitigate the risk of neurological disorders. Full article

Adult mesenchymal stem cells (MSCs) are a promising cell source for tissue regeneration. However, ex vivo expansion results in cell senescence; cells lose their proliferation and differentiation capacity. Fetal MSCs can offer an alternative due to their robust proliferation and differentiation capacities, as well as their immune privilege properties. Given the rejuvenation effect of the decellularized extracellular matrix (dECM) on adult MSCs, it remains unknown whether dECM influences the regenerative potential of fetal stem cells. In this study, passage five fetal nucleus pulposus cells (fNPCs) and fetal synovium-derived stem cells (fSDSCs) were expanded on dECMs deposited by fNPCs (NECM) and fSDSCs (SECM) for one passage, with expansion on tissue culture plastic (Plastic) as a control. We found that dECM-expanded fNPCs and fSDSCs exhibited both similarities and differences in the expression of stemness genes and surface markers. Expanded fNPCs yielded more differentiated pellets after chondrogenic induction but exhibited no adipogenic differentiation following adipogenic induction in both the Plastic and dECM groups than the corresponding fSDSC group. Despite a significant increase in fNPCs, the dECM-expanded fSDSCs exhibited no increase in chondrogenic potential; however, compared to the Plastic group, dECM-expanded fSDSCs exhibited a small increase in osteogenic potential and a great increase in adipogenic potential. These results suggest that fNPCs are more sensitive to NECM rejuvenation for cartilage tissue engineering and regeneration; in contrast, the dECMs exhibited limited effects on fSDSC rejuvenation in a chondrogenic capacity, except for enhanced adipogenic capacity following expansion on SECM. Full article

We report the case of a four-year-old male patient with a complex medical history born prematurely as the result of intrauterine growth restriction due to placental insufficiency. His clinical manifestations included severe neurodevelopmental deficits, global developmental delay, Pierre-Robin sequence, and intractable epilepsy with both generalized and focal features. The proband’s low levels of citrulline and lactic acidosis provoked by administration of Depakoke were evocative of a mitochondrial etiology. The proband’s genotype–phenotype correlation remained undefined in the absence of nuclear and mitochondrial pathogenic variants detected by deep sequencing of both genomes. However, live-cell mitochondrial metabolic investigations provided evidence of a deficient oxidative-phosphorylation pathway responsible for adenosine triphosphate (ATP) synthesis, leading to chronic energy crisis in the proband. In addition, our metabolic analysis revealed metabolic plasticity in favor of glycolysis for ATP synthesis. Our mitochondrial morphometric analysis by transmission electron microscopy confirmed the suspected mitochondrial etiology, as the proband’s mitochondria exhibited an immature morphology with poorly developed and rare cristae. Thus, our results support the concept that suboptimal levels of intrauterine oxygen and nutrients alter fetal mitochondrial metabolic reprogramming toward oxidative phosphorylation (OXPHOS) leading to a deficient postnatal mitochondrial energy metabolism. In conclusion, our collective studies shed light on the long-term postnatal mitochondrial pathophysiology caused by intrauterine growth restriction due to idiopathic placental insufficiency and its negative impact on the energy-demanding development of the fetal and postnatal brain. Full article

Given the broad and intense use of plastic, society is being increasingly affected by its degradation and by-products, particularly by microplastics (MPs), fragments smaller than 5 mm in size, and nanoplastics (NPs), with sizes less than 1 µm. MPs and NPs may enter the body primarily through inhalation, consumption, and skin contact. Once ingested, MPs can penetrate tissues, deviating to other parts of the body and potentially affecting important cellular pathways such as nonconforming chemokine receptors that control the communication between the fetus and the mother. Consequently, the potential health harm induced via MP internalization is a major issue, evidenced by multiple studies demonstrating harmful consequences in diverse animal models and human cells. Here, an overview of the various modes of exposure to MPs and NPs is presented, including inhalation, placental transfer, ingestion, breastmilk consumption, and skin absorption, as well as placental and fetal toxicity due to plastic particles based on animal and in vitro studies. Though MPs in our environment are becoming more recognized, their developmental toxicity is still scarcely known. Besides negatively affecting pregnancy, MPs and NPs have been shown to potentially harm the developing fetus, given their ability to cross the placental barrier. Still, considerable gaps remain in our understanding of the dispersion and toxicity of these particles in the environment and the precise types of NPs and MPs bearing the greatest dangers. As a result, we advocate for larger-scale epidemiological investigations, the development of novel approaches for measuring NP and MP exposures, and the necessity of understanding the toxicity of various kinds of NPs to guide future research efforts. Full article

The concept of Developmental Origin of Health and Disease (DOHaD) postulates that adult-onset metabolic disorders may originate from suboptimal conditions during critical embryonic and fetal programming windows. In particular, nutritional disturbance during key developmental stages may program the set point of adiposity and its associated metabolic diseases later in life. Numerous studies in mammals have reported that maternal obesity and the resulting accelerated growth in neonates may affect adipocyte development, resulting in persistent alterations in adipose tissue plasticity (i.e., adipocyte proliferation and storage) and adipocyte function (i.e., insulin resistance, impaired adipokine secretion, reduced thermogenesis, and higher inflammation) in a sex- and depot-specific manner. Over recent years, adipose progenitor cells (APCs) have been shown to play a crucial role in adipose tissue plasticity, essential for its development, maintenance, and expansion. In this review, we aim to provide insights into the developmental timeline of lineage commitment and differentiation of APCs and their role in predisposing individuals to obesity and metabolic diseases. We present data supporting the possible implication of dysregulated APCs and aberrant perinatal adipogenesis through epigenetic mechanisms as a primary mechanism responsible for long-lasting adipose tissue dysfunction in offspring born to obese mothers. Full article