Search Results (352)

Preeclampsia is a serious pregnancy complication characterised by maternal vascular dysfunction, placental dysfunction, and organ injury, with no effective treatment currently available. Kampo, a system of Japanese traditional medicine comprising standardised herbal formulations, could target pathophysiological pathways driving preeclampsia. We evaluated the effects of select Kampo formulations on markers of preeclampsia using primary human trophoblasts, placental explants, human umbilical vein endothelial cells (HUVECs), and uterine microvascular endothelial cells (UtMVECs). Twelve formulations were initially screened in HUVECs, and six formulations advanced for further study. TNFα was used to induce endothelial dysfunction, and angiogenic, antioxidant, inflammatory, and vascular dysfunction markers were assessed. Overall, Kampo formulations had minimal effect on sFlt-1 expression and only modest effects on sFlt-1 secretion by primary human trophoblast. In contrast, several formulations consistently increased placental growth factor (PlGF) expression and secretion, upregulated HMOX1 in trophoblasts, and enhanced PlGF secretion from placental explants. In endothelial cells, Kampo treatment partially reversed TNFα-induced dysfunction, demonstrated by reduced VCAM1 expression, and additional endothelial cell type-dependent effects on ET-1 and inflammatory pathways. These findings indicate that selected Kampo formulations modulate key pathways involved in the pathophysiology underpinning preeclampsia and warrant further investigation as potential therapeutic candidates. Full article

Pregnancy involves profound metabolic, hormonal, and immunological adaptations essential for fetal development; however, disturbances may lead to complications such as preeclampsia (PE), pre-gestational diabetes, and gestational diabetes mellitus (GDM). These conditions are closely linked to oxidative stress, inflammation, endothelial dysfunction, impaired placentation, and metabolic dysregulation. Consequently, dietary strategies capable of modulating these pathways are of increasing interest. Edible and medicinal mushrooms are widely studied as functional food due to the content of bioactive compounds with antioxidant, anti-inflammatory, immunomodulatory, and metabolic regulatory effects. This review summarizes the nutritional composition of mushrooms and highlights key bioactive constituents with antioxidant and metabolic regulatory properties. Among them, ergothioneine has emerged as a key molecule due to its potent redox-buffering capacity and its potential involvement in the activation of the Nrf2 signaling pathway, a master regulator of cellular antioxidant defense. Through modulation of Nrf2-dependent gene expression, mushroom-derived compounds may contribute to improved cellular resilience against oxidative damage relevant to PE and GDM pathophysiology. Mushroom consumption has additionally been associated with improved glycemic control and enhanced antioxidant defenses in experimental and limited clinical studies, although evidence regarding the prevention or management of hypertensive and metabolic pregnancy complications remains insufficient. Although preclinical findings are promising, clinical evidence remains limited. Further well-designed prospective studies and randomized controlled trials are required to determine efficacy, safety, optimal intake, and active compounds responsible for these effects. Nevertheless, current evidence supports the biological plausibility that edible and medicinal mushrooms are promising dietary modulators of the ergothioneine–Nrf2 axis with potential relevance for maternal–fetal health. Full article

Preeclampsia (PE) is a major pregnancy complication characterized by placental dysfunction and metabolic disturbances. Although mitochondrial abnormalities are frequently observed in PE, the upstream regulatory mechanisms remain incompletely understood. Here, we investigated the potential involvement of BACH1 in trophoblast dysfunction in PE and explored its association with mitochondrial metabolic alterations and protein succinylation. BACH1 expression was assessed in placental tissues and plasma samples from patients with PE, its functional effects were examined in trophoblast cell lines and BACH1 overexpression mouse models, and metabolic, bioenergetic, and succinylation-related alterations were evaluated using multi-omics and functional analyses. BACH1 expression was elevated in PE placentas and correlated with disease severity. In trophoblasts, BACH1 overexpression impaired proliferation, invasion, and trophoblast-mediated angiogenesis and was accompanied by mitochondrial and metabolic abnormalities, while quantitative succinylproteomic analysis revealed widespread alterations in mitochondrial protein succinylation. In vivo, BACH1 overexpression induced key PE-like features, including hypertension, fetal growth restriction, and placental abnormalities, and glycine supplementation partially rescued the trophoblast dysfunction associated with BACH1 overexpression. Together, evidence from clinical samples and experimental models suggests that BACH1 is associated with mitochondrial succinylation remodeling and trophoblast dysfunction in PE, supporting the hypothesis that BACH1-associated metabolic dysregulation and mitochondrial succinylation remodeling may contribute to PE pathogenesis. Further studies are required to establish the causal relevance and clinical significance of these mechanisms in human PE. Full article

Background: Late-onset preeclampsia (LO-PE) is the most prevalent clinical phenotype of preeclampsia and, although traditionally considered less strongly associated with placental dysfunction than early-onset disease, increasing evidence supports the presence of relevant placental alterations. The extracellular matrix (ECM) is a key regulator of villous architecture, tissue mechanics, trophoblast behavior, vascular remodeling, and angiogenesis. This study aimed to characterize ECM remodeling in placentas from women with LO-PE. Patients and Methods: A prospective observational study was conducted in 111 pregnant women, including 68 with LO-PE and 43 healthy controls. Placental samples were collected immediately after delivery. Gene expression of elastogenesis-related markers, cross-linking enzymes, fibrillar collagens, matrix-remodeling regulators, and endothelial–matrix signaling molecules was assessed by RT-qPCR. Protein expression was evaluated by immunohistochemistry. Differences between groups were analyzed using non-parametric tests with Benjamini–Hochberg correction, and correlations among ECM markers were explored using Spearman analysis. Results: LO-PE placentas showed significantly increased expression of tropoelastin (TE), fibulin-4 (FBLN-4), fibulin-5 (FBLN-5), fibrillin-1 (FBN-1), lysyl oxidase (LOX), lysyl oxidase-like 1 (LOXL-1), collagen type I (COL-I), collagen type III (COL-III), and matrix metalloproteinase-2 (MMP-2) at both gene and protein levels. Conversely, gene and protein expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) and epidermal growth factor-like domain 7 (EGFL7) showed a marked decrease in the placentas of pregnant women with LO-PE. These findings indicate enhanced elastogenesis, increased matrix cross-linking, greater fibrillar collagen deposition, and an imbalance in matrix turnover. Correlation analysis further suggested that, although the FBLN-4/FBLN-5 axis remained preserved, LO-PE placentas displayed partial disruption of the broader ECM transcriptional network. Conclusions: LO-PE placentas exhibit a coordinated but dysregulated ECM remodeling phenotype involving elastic, collagenous, proteolytic, and endothelial–matrix regulatory pathways. These alterations support ECM remodeling as a relevant biological feature of LO-PE placental pathophysiology. Full article

Neonatal defense against pathogens relies on maternal antibodies transferred both through the placenta (IgG) and through breast milk (primarily secretory IgA). Maternal IgG antibodies are transferred across the placenta to the fetus mainly via the neonatal Fc receptor (FcRn), which is expressed at high levels in placental syncytiotrophoblasts, and results in the acquisition of maternal-fetal IgG. Transplacental transfer via the FcRn pathway can provide therapeutic proteins and protective antibodies following maternal vaccination. However, maternal IgG antibodies can bind to vaccine antigens such as measles, tetanus, and poliovirus, resulting in rapid clearance through FcgRIIB-mediated inhibition and inadequate B cell activation. In this way, they can inhibit de novo immune responses and significantly reduce vaccine response. On the other hand, the interference that breast milk-derived antibodies may have on vaccine-induced immunity is still largely unknown. Vaccination against influenza, pertussis, and COVID-19 during pregnancy or lactation has been shown to induce the production of protective, pathogen-specific, secretory IgA and IgG antibodies in breast milk. Conversely, studies found that breast milk-derived antibodies of vaccinated mothers reduced vaccine-induced immunity in breastfed infants by accelerating the clearance of vaccine antigen, resulting in reduced antigen availability and reduced plasma cell formation after vaccination. Additional factors in middle- and low-income countries, including environmental (increased microbiome diversity, environmental intestinal dysfunction, malnutrition, co-infections) and breastfeeding practices, may exacerbate the interference effect of maternal antibodies. Current evidence supports that breastfeeding is associated with a reduced immunological response exclusively to the rotavirus vaccine. However, the limited evidence base to date precludes definitive conclusions regarding the role of breast milk-derived antibodies in modulating vaccine-induced immunity. Nevertheless, the evidence suggests that although maternal antibodies may theoretically reduce vaccine immunogenicity, the overall protective benefits of breastfeeding outweigh any potential interference with vaccine responses. Full article

Persisting ethnic disparities in pre-eclampsia (PE), cardiovascular disease (CVD), and maternal mortality call for a paradigm shift in how ethnicity is understood as a risk factor for PE. Starting from a migrant perspective, we argue that the transgenerational experience of maternal stress within shared, yet dynamic ecosocial contexts can be linked to core pathophysiological features of PE. A growing body of evidence suggests how a vicious cycle of chronic maternal stress, cardiovascular dysfunction, placental ER stress, and endothelial dysfunction may serve as a catalyst for the transmission of altered cardiovascular and neuro-endocrine stress reactivity patterns across generations, with a seemingly important role for foetal programming and epigenetics. As these alterations in stress reactivity patterns have in turn been associated with an increased risk of PE and CVD later in life, the resulting transgenerational chain reaction may ultimately allow for ethnic disparities in PE to be traced back to historic, stressful moments in the shared ecosocial contexts of ethnic minority women. Reconceptualising ethnicity as a proxy for the stratified and embodied experience of transgenerational maternal stress within its unique ecosocial contexts, rather than a stand-alone, non-modifiable risk factor, will therefore open new directions for future research, clinical care, and policy interventions aimed at advancing maternal health equity. Full article

Background/Objectives: The soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is an established biomarker in the diagnosis of preeclampsia; however, its significance outside overt hypertensive disorders of pregnancy remains unclear. Emerging evidence suggests that angiogenic imbalance may reflect subclinical placental dysfunction even in otherwise low-risk pregnancies. To investigate associations between the sFlt-1/PlGF ratio and maternal and neonatal outcomes in a low-risk term obstetric population, beyond established diagnostic cut-offs. Methods: This prospective cohort study included 87 women with singleton term pregnancies. Serum sFlt-1 and PlGF concentrations were measured at hospital admission before delivery, and the sFlt-1/PlGF ratio was calculated. The primary outcome was estimated blood loss at delivery. Secondary maternal outcomes included postpartum hemoglobin decline, uterine atony, and fibrinogen concentration. Neonatal outcomes included birthweight, umbilical artery pH, and bilirubin concentration. Multivariable regression models were used to evaluate associations between the ln-transformed sFlt-1/PlGF ratio and outcomes after adjustment for prespecified maternal and obstetric covariates. Results: Each doubling of the sFlt-1/PlGF ratio was associated with greater estimated peripartum blood loss (+78.0 mL, 95% CI 42.1–113.9; p < 0.001), a larger postpartum hemoglobin decline (+0.078 g/dL, 95% CI 0.008–0.148; p = 0.030), lower fibrinogen concentration (−20.7 mg/dL, 95% CI −30.5 to −10.9; p < 0.001), and lower neonatal birthweight (−64.6 g, 95% CI −102.0 to −27.2; p = 0.001). No significant associations were observed for uterine atony, premature rupture of membranes, or umbilical artery pulsatility index above the 75th centile. Conclusions: In low-risk term pregnancies, higher sFlt-1/PlGF ratios were associated with greater estimated peripartum blood loss, lower fibrinogen concentrations, and lower neonatal birthweight. These findings support the hypothesis that variation in angiogenic balance may reflect subclinical placental dysfunction even in apparently uncomplicated pregnancies. Further prospective studies are needed to validate these exploratory observations and determine their clinical relevance. Full article

L-citrulline is a non-protein amino acid with critical roles in perinatal and neonatal physiology through the intestinal–renal arginine–citrulline axis and nitric oxide (NO) production. During pregnancy, L-citrulline supports placental angiogenesis, vascular adaptation, and fetal growth through augmentation of arginine availability and endothelial NO production. In neonates, particularly preterm infants, developmental immaturity of citrulline and arginine synthesis contributes to hypoargininemia and may increase susceptibility to necrotizing enterocolitis, bronchopulmonary dysplasia with pulmonary hypertension, sepsis, and impaired intestinal function. Although L-citrulline has emerged as a promising modulator of NO bioavailability, prior reviews have largely focused on either adult cardiovascular disease or isolated neonatal applications, with limited integration of its mechanistic and translational relevance across the perinatal and neonatal continuum. Collectively, current evidence supports L-citrulline as a promising translational target in maternal–fetal and neonatal medicine because of its central role in vascular, inflammatory, and metabolic regulation. However, adequately powered clinical trials are needed to define optimal dosing, timing, patient selection, and long-term outcomes before routine clinical implementation can be recommended. This review provides a comprehensive evaluation of L-citrulline metabolism and its therapeutic potential from pregnancy through neonatal life, with emphasis on the intestinal–renal arginine–citrulline axis, endothelial function, and NO-mediated vascular regulation. We specifically examine the role of citrulline in key pathophysiologic mechanisms underlying maternal and neonatal disease, including endothelial dysfunction, impaired NO bioavailability, inflammation, oxidative stress, and abnormal placental vascular remodeling. Full article

Background: Precision medicine aims to improve early, individualized risk stratification using biologically relevant biomarkers. In early pregnancy, markers reflecting placental function remain limited. Kisspeptin, a placentally derived peptide that rises during normal gestation, has emerged as a potential indicator of pregnancy viability. Objectives: We aimed to evaluate evidence on maternal serum kisspeptin levels and placental KISS1/KISS1R expression in early pregnancy loss, and to assess its potential relevance as a precision biomarker within personalized pharmacy and individualized monitoring frameworks. Methods: A systematic search of PubMed, Scopus, Web of Science, and Google Scholar (up to 2025) was conducted according to the PRISMA 2020 guidelines. Studies assessing circulating kisspeptin and/or placental expression in early pregnancy loss versus viable pregnancies were included. A formal meta-analysis was not performed due to substantial heterogeneity in study design, biological material, assay methods, gestational age, and outcome reporting formats. Under these conditions, quantitative pooling was considered methodologically inappropriate; therefore, qualitative synthesis was performed. Results: Six studies met the inclusion criteria. Most reported significantly lower maternal serum kisspeptin levels in early pregnancy loss, with good discriminatory accuracy. Immunohistochemical analyses showed reduced placental and choriodecidual KISS1/KISS1R expression in miscarriage and recurrent pregnancy loss, indicating disrupted local signaling. Concordant systemic and tissue findings suggest that circulating kisspeptin reflects placental dysfunction. Conclusions: Kisspeptin appears to be a promising precision biomarker for monitoring early pregnancy viability and supporting individualized pharmaceutical care. Standardized assays and large prospective studies are needed before routine clinical implementation. Full article

Background/Objectives: Autophagy is a highly conserved eukaryotic cellular process whose dysfunction results in human pathologies including cancer and neurodegenerative disease. First identified in yeast, ATG genes are central players in autophagy. Mutations in core autophagy genes ATG5 and ATG7 have been previously reported to cause rare genetic disorders with autosomal recessive inheritance. Methods: Here we report, for the first time, variants in human ATG9B gene as causative factors for a rare neurodevelopmental disease with autosomal recessive inheritance. Three distinct mutations were detected in three independent families with consanguinity, five patients affected in total. Results: The first variant is an 11-nucleotide deletion resulting in a frameshift. A premature stop codon is added and the C-terminal cytosolic domain of ATG9B protein is truncated. The second one is a point mutation that changes a critical amino acid in the transmembrane domain. The third variant is a 2-nucleotide deletion causing a different truncation product. Patients presented with diverse neurodevelopmental anomalies including intellectual disability, behavioral abnormalities, congenital cerebellar ataxia, mild cerebellar atrophy, and microcephaly. Since human ATG9B is expressed specifically in the placenta, we hypothesized that the disease pathology originates during placental development. To characterize the effects of the first frameshift mutation and gain insight into the specific functions of ATG9B in a physiological setting, we used mammalian cells and a knock-in mouse model. Truncated ATG9B was not stable when expressed in cells. It was localized to perinuclear vesicles like the WT protein, but not to peripheral vesicles. Homozygous knock-in mice were viable, fertile, and displayed no gross phenotypical abnormalities. Histomorphometry analysis of the placenta layers did not reveal a significant difference between mutant and control embryos. The assessments of neurobehavioral tests were similar in wild-type and homozygous knock-in mice. However, knock-in mice had a reduced fear memory trend, which is an amygdala-involved response. Conclusions: In this study, we describe a new rare disease linked to ATG9, including cerebellar ataxia and atrophy, as described for ATG5 and ATG7. Full article

Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality, yet reliable first-trimester biomarkers for early prediction remain lacking. Growing evidence suggests that placental dysfunction is a central pathological driver of FGR. Therefore, placenta-derived proteins in maternal circulation may serve as mechanistically informative biomarkers for early detection. Here, we aimed to evaluate several placenta-relevant molecules as biomarkers for predicting isolated FGR and its subtypes. In this prospective nested case–control study, we included singleton pregnancies that underwent Down screening in the first trimester and were subsequently diagnosed with FGR (n = 50, including early-onset FGR [EFGR] and late-onset FGR [LFGR]) and healthy pregnancies (n = 100). Pregnancies with maternal comorbidities or fetal anomalies were excluded. Maternal serum protein concentrations were measured using ELISA kits. There were no significant differences in placenta-specific protein 1 (PLAC1) or netrin-1 between the two groups. By contrast, maternal soluble programmed death-ligand 1 (sPD-L1) levels were significantly lower in overall FGR (p < 0.001) and FGR subtypes (p = 0.002) than in controls. Circulating sPD-L1 levels were positively correlated with gestational age at delivery and birth weight Z score. Each one-unit increase in sPD-L1 was associated with lower odds of overall FGR (Odd ratio, OR 0.33), EFGR (OR 0.17), LFGR (OR 0.43), birth weight Z score 3–10% (OR 0.30), and neonatal intensive care unit (NICU) admission (OR 0.38). Moreover, first-trimester sPD-L1 predicted overall FGR (area under the receiver operating characteristic curve, AUC 0.75), EFGR (AUC 0.84), LFGR (AUC 0.70), birth weight Z score 3–10% (AUC 0.75), and NICU admission (AUC 0.67). Collectively, decreased maternal circulating sPD-L1 in early pregnancy may serve as a potential biomarker for isolated FGR, warranting validation in larger multicenter mechanistic studies. Full article

Spontaneous abortion (SA) is intimately associated with ferroptosis in placental trophoblasts. Asperosaponin VI (AVI), a major active triterpene saponin extracted from Dipsacus asperoides, has emerged as a promising therapeutic candidate for SA; however, its precise molecular mechanisms remain poorly elucidated. This study aimed to investigate the protective efficacy of AVI against SA and clarify its underlying pathways. In vivo, an SA model was established via the subcutaneous administration of bromocriptine. AVI intervention significantly reduced the embryo resorption rate and ameliorated placental injury. Biochemically, AVI attenuated the accumulation of MDA and Fe²⁺, downregulated pro-ferroptotic markers (TFR-1 and ACSL4), and systematically modulated the expression of SLC7A11 alongside the ferroptosis-related KEAP1/NRF2/GPX4 signaling axis. In silico analyses, including molecular docking and molecular dynamics simulations, confirmed a robust binding affinity between AVI and NRF2. In vitro, AVI dose-dependently reversed erastin-induced trophoblast dysfunction and mitochondrial impairment, while effectively abrogating the ferroptosis-associated overproduction of ROS, Fe²⁺, and MDA. Crucially, pharmacological inhibition of NRF2 by ML385 partially negated these cytoprotective effects. Comprehensive molecular analyses (RT-qPCR, IF and Western blotting) revealed that AVI suppressed KEAP1 while concomitantly upregulating NRF2, GPX4, and SLC7A11. In conclusion, AVI prevents SA by suppressing trophoblast ferroptosis through KEAP1/NRF2/GPX4 signaling, offering a novel therapeutic approach. Full article

Preeclampsia (PE) is a severe pregnancy-specific hypertensive disorder characterized by immune microenvironment dysregulation at the maternal–fetal interface, with decidual macrophage phenotypic imbalance being a key pathological feature. The Ghrelin/growth hormone secretagogue receptor-1a (GHSR-1a) axis exerts immunomodulatory and anti-inflammatory effects, but its role in regulating decidual macrophage infiltration and phenotypic marker expression in PE remains unclear. In this study, we first detected the expression of the Ghrelin/GHSR-1a axis in decidual tissues from 10 healthy pregnant women and 12 PE patients via immunohistochemistry (IHC). We then established a lipopolysaccharide (LPS)-induced PE-like rat model to investigate the axis’s functional role and underlying mechanisms. Intriguingly, clinical analysis revealed a severity-dependent compensatory escalation of the Ghrelin/GHSR-1a axis in PE decidual tissues, potentially representing an endogenous antagonistic response to pregnancy-associated pathological stress. In the animal model, exogenous Ghrelin supplementation reversed LPS-induced PE-like phenotypes, including hypertension, proteinuria, fetal growth restriction (FGR), and placental dysfunction, and alleviated pathological damage to the maternal liver, kidney, and placenta. Mechanistically, Ghrelin modulated decidual macrophage phenotypic marker expression by downregulating the M1 marker CD86 and upregulating the M2 marker CD163 and promoted trophoblast invasion and spiral artery remodeling by restoring laminin, α-cytokeratin 7 (α-CK7), and α-smooth muscle actin (α-SMA) expression in placental tissue. All protective effects of Ghrelin were abrogated by co-administration of D-lys-3-GHRP-6, a specific GHSR-1a antagonist, confirming the dependence on the Ghrelin/GHSR-1a axis. Collectively, our findings suggest that the Ghrelin/GHSR-1a axis is compensatorily upregulated in PE and may exert a protective role by regulating decidual macrophage phenotypic marker expression and improving placental function, providing preliminary evidence that this axis merits further investigation as a potential research target for PE. Full article

Gestational diabetes mellitus (GDM) is increasingly recognized as a complex pathology rooted in systemic and organelle-level dysfunction, specifically involving chronic low-grade inflammation (CLGI), mitochondrial impairment, and endoplasmic reticulum (ER) stress. Central to this pathophysiology is mitochondrial dysfunction, characterized by reduced respiration, impaired metabolic flexibility, and dysregulated fission/fusion machinery, which fuels a self-perpetuating cycle of reactive oxygen species (ROS) production. Concurrently, chronic ER stress triggered by hyperglycemia and lipotoxicity activates the unfolded protein response (UPR), further amplifying redox imbalance through the Endoplasmic Reticulum Oxidoreductin 1/Protein Disulfide Isomerase (ERO1/PDI) axis and bridging metabolic toxicity to inflammation via c-Jun N-terminal kinase (JNK) and nuclear factor kappa-light-chain–enhancer of activated B cells (NF-κB) signaling. The Advanced Glycation Endproducts (AGEs) and the Receptor for Advanced Glycation Endproducts (RAGE) axis act as a molecular catalyst that sequester antioxidants and drive pro-inflammatory feedback loops. These converging mechanisms culminate in profound placental maladaptation, including structural abnormalities like chorangiosis and functional defects in nutrient transport mediated by hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. This review article provides insight into recent evidence to elucidate the meta-inflammatory environment of GDM, where modest but sustained elevations in biomarkers like Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) disrupt redox homeostasis and impair insulin signaling pathways through the activation of stress-sensitive kinases. By integrating these molecular perspectives, the article underscores the necessity of targeting the systemic inflammatory and oxidative continuum spanning pre-conception to the antenatal period through lifestyle interventions and emerging therapeutic strategies to mitigate GDM risk and improve maternal–fetal outcomes. Full article

Background: Micro- and nano-plastics (MNPs) are pervasive environmental contaminants that accumulate in various tissues, including the placenta. Experimental and clinical studies suggest potential cytotoxic, oxidative, and inflammatory effects that may lead to placental dysfunction and adverse obstetric outcomes. However, high-quality evidence on the clinical relevance of MNPs exposure during pregnancy remains scarce, underscoring the need for systematic evaluation of their impact on maternal and fetal health. Methods: The databases PubMed, ScienceDirect, CENTRAL, Embase, MDPI and Google Scholar were searched for studies published up to September 2025 investigating the relationship between MNPs and obstetric outcomes. Results: Twelve studies were included in this review, with half employing an observational design in human subjects and the other half using experimental studies in murine models. Although the available evidence is limited, there are studies reporting the association between MNPs exposure and premature birth, low birth weight, intrauterine growth restriction, and miscarriage. The most prevalent polymer detected was polyethylene, and the most commonly used MNPs detection techniques were Raman microspectroscopy, digital microscopy, Fourier Transform Infrared, and Pyrolysis gas chromatography-mass spectrometry. Conclusions: This systematic review summarizes current limited insights on the potential effects of MNPs on obstetric outcomes, highlighting possible associations with low gestational age, low birth weight, intrauterine growth restriction, and miscarriage. Findings do not allow causal inference due to heterogeneity in study design, exposure assessment, contamination control, and analytical methodologies. Full article