Search Results (765)

Galectins represent a family of proteins which are capable of specifically binding to beta-galactoside-containing sugar molecules, known as glycans. Galectins possess carbohydrate recognition domains (CRDs) that fundamentally determine their ability to bind to sugars. Galectin-14 (Gal-14) and galectin-16 (Gal-16) are members of the galectin family that is particularly associated with the placenta. The galectins in the placenta constitute a specialized subgroup functioning at the maternal–fetal interface. They are expressed primarily in the syncytiotrophoblasts. This trophoblast layer is in direct contact with maternal blood and plays a crucial role in the metabolic, hormonal and immunological interactions between the fetus and the pregnant woman. In order to prepare this structured narrative review, we conducted a structured literature search across the MEDLINE (PubMed), Embase, Cochrane Library and Web of Science Core Collection databases; the final search has been performed on 1 July 2026. The search strategy has combined the terms galectin-14/LGALS14 and galectin-16/LGALS16 with terms related to the placenta, trophoblast, pregnancy, placentation and pregnancy complications. Search results were imported into Mendeley Reference Manager to remove duplicates, and the reference lists of relevant review articles and studies were manually screened. Two reviewers (Z.K. and A.S.) independently screened the titles and abstracts and subsequently evaluated the potentially relevant full-text articles. The final evidence synthesis included primary studies that directly investigated the expression, function, regulation, or clinical associations of LGALS14 or LGALS16; secondary publications were used for background and contextual information. In experimental studies, galectin-14 has been linked to trophoblast migration and invasion—involving mechanisms such as the PI3K/Akt signaling pathway, MMP-9 and N-cadherin—as well as to the modulation of activated maternal immune cell function. Galectin-16 is structurally more distinct and exhibits reduced classical β-galactoside-binding capacity; it appears to be closely associated with trophoblast differentiation and syncytialization, presumably through intracellular protein interactions. Altered expression of placenta-specific galectins has been observed in preeclampsia and fetal growth restriction; however, the causal relationship remains unclear. Clinical evidence regarding their use as biomarkers is emerging at this time; therefore, neither galectin-14 nor galectin-16 can be currently considered as a validated, clinically applicable biomarker. Altogether, available evidence mandates further study of galectin-14 and galectin-16, as they may be important regulators of placental biology and potential biomarker candidates. However, their physiological functions and clinical utility have not yet been sufficiently confirmed; therefore, further prospective and functional studies are required. The strongest putative mechanistic link to the development of preeclampsia exists for galectin-14, primarily involving trophoblast migration and invasion as well as PI3K/Akt-related signaling pathways. In contrast, evidence in connection with the direct role of galectin-16 is limited at present. Full article

The field of neuroplacentology is a growing area that focuses on the influence of placental function on brain development. This field has expanded our understanding of the placenta’s crucial role in proper neurodevelopment as well as placental anomalies that increase the risk of adverse neurodevelopmental outcomes. Neuroplacentology studies have revealed distinct roles of placentally provided hormones and nutrients in neurodevelopment whose disruption by perinatal problems, including inflammation, can increase the risk of neurodevelopmental disorders such as autism spectrum disorder and ADHD. Placental insulin-like growth factor signaling significantly influences brain growth in animal model studies and is tightly linked with human neurodevelopmental outcomes. Insulin-like growth factor signaling is well-established as a regulator of placental function and is fundamental in fetal brain cell developmental processes and plays a role in inflammation. Placental insulin-like growth factor signaling underlies the placental production and delivery of hormones and nutrients that are necessary for fetal neural cell proliferation, differentiation, and growth. It is especially important to study this pathway in the placenta due to aberrant insulin-like growth factor signaling found in conditions such as preterm birth, fetal growth restriction, gestational diabetes, and obesity. All these conditions are linked to a greater risk for neurodevelopmental disorders, neuroinflammation, and other anomalies. This research subfield has also revealed sex differences in the insulin-like growth factor signaling pathway that will contribute to understanding the etiologies of these conditions. This area of study has and will continue to identify specific mechanisms, many currently in model systems, which could eventually be leveraged in preventative and interventive care to improve neurodevelopmental outcomes. Full article

Background/Objectives: Prior research suggests that fetal intra-abdominal umbilical vein varix (FIUVV) is associated with an increased risk of structural anomalies, aneuploidy, and poor obstetrical outcomes such as growth restriction and demise. Data in prior studies, however, are limited. The aim of this study is to determine the natural progression of FIUVV and its association with maternal and antenatal complications. Methods: This is a retrospective cohort study of singleton pregnancies that received an ultrasound between July 2020 and June 2023. FIUVV was diagnosed based on the presence of a focal intra-abdominal vein dilation measuring >9 mm or >50% wider than the diameter of the intra-hepatic umbilical vein. Controls were matched 1:1 based on same date as the cases and by similar gestational age. Maternal and fetal outcomes were collected. Results: A total of 105 pregnancies complicated by FIUVV met inclusion criteria, and 105 controls were identified. Diagnosis was most commonly obtained at 32 gestational weeks with average dilation at 11.2 mm. Concurrent structural defects were detected in 19 (18.1%) fetuses. Compared to controls, pregnancies complicated by FIUVV had similar rates of diabetes, hypertensive disorders, COVID-19, active smoking, and abnormal genetic screening. There were also similar rates of fetal growth restriction, large-for-gestational-age fetuses, and oligohydramnios. Pregnancies complicated by FIUVV were more likely to have polyhydramnios compared to controls (p < 0.01). Conclusions: In the large cohort of FIUVV, outcomes were favorable. FIUVV was not associated with common maternal co-morbidities. Polyhydramnios was more common in pregnancy complicated by FIUVV, but fetal growth abnormalities were similar compared to controls. Full article

Background/Objectives: Artificial intelligence (AI)-assisted automatic fetal measurements during ultrasound evaluation have become a major subject of interest. Most publications include systems developed and tested for a single anatomical component. In routine clinical practice, multiple biometric parameters are required for fetal weight estimation. Our objective is to assess the studies that incorporated three or more standard plane fetal automatic measurements with the help of AI systems in the second and third trimesters. Methods: We performed a systematic review of the published research focusing on automated AI systems analyzing at least three standard fetal biometric parameters or their corresponding standard ultrasound planes for fetal biometric, gestational-age, or fetal-growth assessment. The literature screening had to meet the predefined inclusion and exclusion criteria. Results: Nineteen studies, comprising more than 730,000 ultrasound images, met the inclusion criteria, and eighteen studies compared automated measurements with manual reference measurements. Overall, the included studies reported favourable performance for automated assessment of biparietal diameter, head circumference, abdominal circumference, and femur length, although substantial heterogeneity was observed in study design, AI architecture, validation methodology, and reported performance metrics. Conclusions: Automated AI systems show promising performance for assessing multiple standard fetal biometric parameters and may improve measurement consistency and examination efficiency. However, substantial heterogeneity in datasets, model architectures, and outcome reporting restricts direct comparison and the certainty of the evidence. Standardized reporting and prospective multicentre evaluation across gestational ages (GA), ultrasound systems, and operators are needed before these systems can be recommended for routine clinical use. Full article

Oxidative stress is a well-recognized contributor to male reproductive dysfunction, yet discussion of this mechanism has focused almost exclusively on sperm damage. This focus overlooks the somatic and stromal networks that support testicular development, steroidogenesis, tissue architecture, and erectile function. Platelet-derived growth factor receptor alpha (PDGFRα) is expressed in heterogeneous interstitial and progenitor-enriched populations and has established roles in testicular development. This narrative review examines the evidence on PDGFRα in male reproductive tissues and considers the potential relevance of redox mechanisms identified predominantly in other organ systems. Genetic studies show that Pdgfa deficiency impairs the postnatal establishment of the adult Leydig-cell population, whereas Pdgfra deficiency disrupts fetal testis cord organization and Leydig-cell differentiation. Studies of the adult testis document receptor localization and, in cell-based models, downstream signaling capacity. Preclinical work has further identified PDGFRα-positive cavernosal fibroblasts associated with vascular remodeling in erectile dysfunction, although a receptor-specific function for these cells remains unproven. We propose that PDGFR-associated redox signaling may shape stromal responses to injury in the testis and penis; however, direct evidence for this mechanism in male reproductive tissue is currently lacking. Testing this hypothesis will require cell-resolved measurements of receptor phosphorylation and localized reactive oxygen species, together with lineage-restricted, receptor-specific perturbation. Establishing whether such a pathway exists could open a mechanistic link between oxidative stress and stromal, rather than purely germ-cell, contributions to male reproductive dysfunction—with implications for both testicular endocrine failure and vasculogenic erectile dysfunction. Full article

Background: Maternal undernutrition is associated with impaired fetal growth and adverse pregnancy outcomes, but the effects of food-based nutritional interventions during pregnancy remain uncertain. This systematic review and meta-analysis evaluated their effects on maternal and neonatal outcomes using evidence exclusively from randomized controlled trials (RCTs). Methods: PubMed, Embase, Scopus, and the Cochrane Library were searched from inception to 15 July 2026 for RCTs comparing food-based nutritional interventions with standard care, no supplementation, micronutrient supplementation, or an alternative nutritional intervention. Risk ratios (RRs) for binary outcomes were pooled using the Mantel–Haenszel method, while mean differences (MDs) for continuous outcomes were pooled using the inverse-variance method. Restricted maximum-likelihood random-effects models were applied, and heterogeneity was assessed using I² and Cochran’s Q test. The protocol was registered in PROSPERO (CRD420261465279). Results: Six RCTs comprising 6245 participants were included, of whom 3150 (50%) received a nutritional intervention. Nutritional interventions increased birth weight (MD 51.49 g; 95% CI 22.87–80.11; I² = 42.7%; p < 0.01) and birth length (MD 0.29 cm; 95% CI 0.14–0.45; I² = 21.6%; p < 0.01). No significant effects were observed on birth head circumference (MD −0.14 cm; 95% CI −0.62 to 0.34; I² = 73.9%; p = 0.57), low birth weight (RR 0.76; 95% CI 0.35–1.68; I² = 64.2%; p = 0.28), stillbirth (RR 0.96; 95% CI 0.78–1.19; I² = 0%; p = 0.61), or miscarriage (RR 0.83; 95% CI 0.35–1.97; I² = 0%; p = 0.45). Conclusions: Food-based nutritional intervention strategies were associated with small statistically significant increases in birth weight and birth length; however, the clinical importance of differences of approximately 51 g and 0.29 cm remains uncertain. Evidence was inconclusive for low birth weight, head circumference, stillbirth, and miscarriage. Full article

Objective: Sonographic evaluation of the fetus and estimation of fetal weight are integral components of modern obstetric practice. Estimated fetal weight (EFW) plays a crucial role in predicting macrosomia, diagnosing intrauterine growth restriction, and monitoring fetal development. This study aimed to improve birth-weight prediction in low-risk term pregnancies by combining conventional fetal biometry with maternal anthropometry and selected fetal soft-tissue and cardiac measurements. Materials and Methods: In 94 low-risk, term singleton pregnancies scheduled for elective cesarean delivery, standardized prenatal ultrasound was performed within 24 h before birth by a single operator. Neonatal anthropometry was obtained within 6 h postnatally. Multiple linear regression was used to develop conventional and extended prenatal birth-weight prediction models with actual birth weight as the dependent variable, and their performance was compared with Hadlock EFW. Results: Mean actual birth weight was 3178.9 ± 359.5 g and mean Hadlock EFW was 3201.6 ± 399.7 g. Hadlock estimation correlated strongly with birth weight (r = 0.826) and had a mean absolute error (MAE) of 181.0 g. Abdominal circumference was the strongest conventional sonographic correlate of birth weight. The conventional prenatal Model 2 achieved R² = 0.710 and MAE = 150.1 g. The extended prenatal Model 5, which combined conventional biometry with symphysis-fundal height, femoral soft-tissue thickness, right atrial area, maternal abdominal fat thickness, and aortic valve diameter, showed the best performance (R² = 0.783; MAE = 133.2 g). Its optimism-corrected and repeated cross-validated R² values were 0.739 and 0.725, respectively. Conclusions: The newly proposed formulas, particularly Model 5, demonstrated better internally validated predictive performance than the Hadlock baseline in this cohort, suggesting that the integration of selected maternal anthropometric and additional fetal ultrasonographic measurements with conventional biometry may improve birth-weight estimation. These findings warrant external validation in larger and more diverse populations prior to clinical implementation. Full article

Background: Congenital heart disease (CHD) co-occurring with fetal growth restriction (FGR) is clinically important but incompletely characterized. We assessed the proportion and subtype spectrum of CHD in term-born children with FGR, and factors associated with its presence and complexity. Methods: Retrospective analysis of 375 term singleton children with documented FGR at a tertiary pediatric center. CHD required echocardiographic confirmation; isolated patent foramen ovale was excluded. Patients with multiple lesions were hierarchically classified as simple or complex. Multivariable logistic regression was restricted to characteristics available at or before birth. Results: CHD was confirmed in 96/375 children (25.6%): 71 (74.0%) simple, 25 (26.0%) complex. Atrial septal defect and patent ductus arteriosus were most frequent (each 45.8%), followed by patent foramen ovale (44.8%) and ventricular septal defect (32.3%). Severe FGR (aOR 2.012, 95% CI 1.222–3.313; p = 0.006) and genetic syndrome (aOR 5.969, 95% CI 2.565–13.889; p < 0.001) were independently associated with CHD presence. Within the CHD subgroup, genetic syndrome was also associated with complex disease (aOR 5.156, 95% CI 1.651–16.104; p = 0.005). Diagnosis occurred before six months in 95.8%. Hospitalization outcomes and comorbidity burden did not differ by complexity. Conclusions: FGR severity and genetic syndrome were both independently associated with the presence of a cardiac defect, and genetic syndrome was further associated with its complexity. These findings support targeted rather than universal echocardiographic assessment. Directionality cannot be established from postnatal data. Full article

Objectives: To characterize the clinical and genetic features of Phelan–McDermid syndrome (PMS) in a Chinese prenatal and postnatal cohort, explore genotype–phenotype correlations, and provide evidence to support prenatal genetic counseling. Methods: G-banded karyotyping, single-nucleotide polymorphism arrays (SNP arrays), copy number variation sequencing, and trio whole-exome sequencing were used for genetic diagnosis. Fifteen patients with PMS (11 prenatal and 4 postnatal) were retrospectively enrolled. Genomic visualization, protein structural prediction, and phenotypic heatmap analyses were conducted to analyze genotype–phenotype associations. Results: The prenatal and postnatal detection rates of PMS were 0.061% and 0.49%, respectively. Only 13.3% of cases were detected by karyotyping, whereas 14 cases were confirmed by SNP array analysis. All 22q13 deletions (69.4 kb–8.5 Mb) involved SHANK3, and all copy number variants were de novo. A novel SHANK3 frameshift variant, c.3513_3514delCC, was identified and predicted to result in protein truncation leading to intellectual disability. Prenatal cases mainly presented non-specific ultrasound anomalies (63.6%, 7/11), with fetal growth restriction, renal malformations, and cardiovascular defects being the most frequent findings. A notable 36.4% (4/11) of prenatal cases were complicated by missed abortion, whereas postnatal patients showed predominant neurodevelopmental impairments. In our cohort, larger deletions were observed in cases presenting with more extensive multisystem involvement, a pattern that mirrors findings from recent large-cohort studies. central nervous system abnormalities were predominantly linked to SHANK3 haploinsufficiency, while multi-system malformations seemed to correlate with the cumulative loss of multiple genes across the 22q13 region, in keeping with current hypotheses on contiguous gene effects. Conclusions: PMS presents obvious prenatal–postnatal phenotypic heterogeneity. SHANK3 is the core pathogenic gene, and deletion may influence the extent of multisystem involvement. Combined genetic testing can improve the accuracy of prenatal diagnosis and counseling for PMS. Full article

Background/Objectives: Sickle cell thalassemia (HbSβ-thal) and related sickle cell disease (SCD) genotypes are associated with substantial maternal, fetal, and neonatal morbidity during pregnancy. This systematic review aimed to summarize pregnancy outcomes and clinical management strategies in women with HbSβ-thal and related hemoglobinopathies, with an additional narrative comparison to sickle cell trait (SCT)—a distinct, heterozygous, and generally benign carrier state that is not a form of SCD. Methods: A systematic literature search was conducted in PubMed, MEDLINE, Web of Science, EMBASE, and Scopus for studies published between 2016 and 2026 using terms related to sickle cell anemia, sickle cell disease, sickle cell thalassemia, HbS/beta-thalassemia, sickle cell trait, pregnancy outcomes, maternal complications, neonatal outcomes, fetal outcomes, and clinical/obstetric management. Studies reporting maternal, fetal, or neonatal outcomes were included, while letters, commentaries, conference abstracts, and presentations were excluded. Study selection followed PRISMA principles. Risk of bias was assessed using appropriate tools according to study design, including the Newcastle–Ottawa Scale (NOS), AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews), SANRA (Scale for the Assessment of Narrative Review Articles), and CARE (CAse REport) guidelines. SCT terms were included in the same search strategy, so that SCT studies were retrieved and screened through the same PRISMA process and are reported as a prespecified comparator subgroup. Results: Fourteen studies met the inclusion criteria: ten reporting outcomes in HbSβ-thal and related SCD genotypes and four reporting outcomes in SCT. The most frequently reported maternal complications were severe anemia, vaso-occlusive crises (VOCs), preeclampsia, thromboembolic events, infections, acute chest syndrome, cesarean delivery, and postpartum complications, which led to a significant increase in hospitalization rates. Fetal and neonatal outcomes were also unfavorable, with increased rates of preterm birth, low birth weight, intrauterine growth restriction, placental insufficiency, and neonatal intensive care admission. Placental vascular malperfusion and low maternal hemoglobin were important mechanisms underlying fetal growth restriction. By contrast, the included SCT literature suggested outcomes generally closer to the general obstetric population, with a smaller number of specific associations (e.g., preeclampsia, intrauterine fetal death) reported inconsistently across studies. Conclusions: Pregnancies complicated by HbSβ-thal and related hemoglobinopathies remain high-risk and require early identification, preconception counseling, multidisciplinary care, close antenatal surveillance, individualized transfusion strategies, and postpartum thromboprophylaxis when indicated. Prospective genotype-specific studies, particularly isolating HbSβ-thal from broader SCD cohorts, are needed to optimize evidence-based management. Full article

Background/Objectives: To investigate maternal serum Isthmin-1 (ISM1) levels in pregnancies complicated by fetal growth restriction (FGR) and to evaluate its potential discriminatory performance for FGR. Methods: This prospective cross-sectional study included 44 pregnant women with late-onset FGR and 43 gestational age-matched healthy controls. FGR was diagnosed according to one of two criteria: (1) estimated fetal weight (EFW) below the 3rd percentile, or (2) EFW between the 3rd and 10th percentile with at least one abnormal Doppler finding (Umbilical Artery Pulsatility Index (UA-PI), Middle Cerebral Artery Pulsatility Index (MCA-PI), or Cerebroplacental Ratio (CPR). Maternal serum ISM1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Ultrasonographic parameters, Doppler indices, and perinatal outcomes were compared between groups. Correlation and receiver operating characteristic (ROC) analyses were performed to assess diagnostic performance. Results: Maternal ISM1 levels were significantly lower in the FGR group compared with controls [10.63 (9.95–12.10) vs. 12.40 (10.75–13.25) ng/mL, p = 0.003]. ISM1 correlated negatively with FGR presence (r = −0.318, p = 0.003) and positively with EFW percentile (r = 0.235, p = 0.028). ROC analysis showed moderate diagnostic accuracy Area Under the Curve (AUC) = 0.684, 95% CI: 0.575–0.779) with 70.5% sensitivity and 72.1% specificity at a cut-off ≤11.5 ng/mL. No significant association was found between ISM1 and composite adverse perinatal outcomes. Conclusions: Levels of ISM1 in maternal serum were found to be significantly lower in pregnancies complicated by FGR, supporting a potential association between ISM1 and impaired fetal growth. However, its moderate diagnostic performance and lack of association with adverse perinatal outcomes indicate that ISM1 should currently be regarded as a promising exploratory biomarker rather than a standalone diagnostic or prognostic marker. Further studies are needed to validate these findings and to determine whether ISM1 provides additional value when combined with established Doppler and angiogenic markers. Full article

Vanishing twin syndrome (VTS) denotes the spontaneous loss of one conceptus from an initially recognized multiple pregnancy, most often during the first trimester. Its clinical relevance has increased with in vitro fertilization and embryo transfer (IVF-ET), as multiple embryo transfer creates the substrate for dizygotic VTS, while blastocyst transfer may be followed by monozygotic splitting and serial early ultrasonography increases detection. However, the literature remains heterogeneous, with empty gestational sacs, losses after fetal cardiac activity, and later single fetal demise often grouped together despite different biological and prognostic implications. New evidence published in recent years on frozen embryo transfer outcomes, cell-free DNA screening, and early childhood development warrants an updated synthesis of vanishing twin syndrome to inform individualized risk assessment, counselling, and standardized research reporting. Overall, the surviving singleton appears to have a lower risk than an ongoing twin pregnancy but a higher risk than a primary singleton, particularly for preterm birth, low birthweight, and small-for-gestational-age birth, with risk increasing when loss occurs after fetal cardiac activity or later in gestation. Nevertheless, evidence is not unanimous, as several well-characterized cohorts and earlier meta-analyses reported no measurable perinatal disadvantage. Two reports from a single tertiary center, based on substantially overlapping recruitment periods, further suggest that VTS may be proportionally less frequent among established twin pregnancies after IVF/ICSI than after spontaneous conception, while IVF-associated VTS has been linked to placental abnormalities, diabetes, and fetal growth restriction; this observation requires independent confirmation. Contemporary frozen embryo transfer cohorts indicate that VTS remains relevant in modern practice, whereas limited long-term data have not demonstrated impaired early childhood growth or development. Management should document the initial number of gestational sacs, embryonic structures, cardiac activity, chorionicity, and timing of loss, while adapting aneuploidy screening to residual trophoblastic DNA and individualizing fetal-growth surveillance. Elective single-embryo transfer remains the most effective preventive strategy, although it cannot eliminate monozygotic twinning. Standardized definitions and long-term offspring follow-up are needed. Full article

Non-communicable diseases remain the dominant cause of adult morbidity and mortality, yet cardiometabolic, vascular and renal risk may originate before birth. This structured narrative review critically evaluates human evidence linking pregnancy-related exposures, placental pathophysiology and later offspring health within a maternal–placental–fetal–life-course framework. Evidence published from 2020 to 2026 was emphasised, while seminal earlier cohorts were retained when they provided uniquely long follow-up or direct placental measurements. The most consistent associations concern maternal obesity, gestational diabetes, excessive gestational weight gain and hypertensive disorders, which are linked with higher offspring blood pressure, greater adiposity and adverse glucose–insulin profiles. Human placental studies implicate vascular malperfusion, altered nutrient transport, inflammatory and oxidative signalling, endocrine function and epigenetic regulation. Few studies, however, have measured the prenatal exposure, a specific placental phenotype and a long-term offspring outcome within the same longitudinal design; most proposed placental pathways are supported by convergent evidence or biological plausibility rather than demonstrated mediation. Preterm birth and fetal growth restriction are clinically observable, etiologically heterogeneous sentinel phenotypes, not obligatory mediators. Placental and offspring epigenetic signatures, telomere biology and mitochondrial function represent distinct domains of biological embedding; their causal and prognostic significance remains uncertain. Longitudinal studies integrating maternal exposures, placental histopathology and molecular phenotypes, fetal organ development, childhood cardiometabolic trajectories and adult clinical outcomes are needed to determine whether, and under what circumstances, the placenta plays an intermediary role rather than merely serving as a marker of an adverse pregnancy environment. Full article

Background: Fetal growth restriction (FGR) is associated with placental dysfunction and adverse perinatal outcomes. Although insulin-like growth factor-1 (IGF-1) signaling is important for placental and fetal development, the mRNA expression, immunopositivity and potential biological significance of specific IGF-1 isoforms in FGR remain incompletely characterized. This study investigated placental IGF-1Eb mRNA expression and immunopositivity in FGR pregnancies compared with appropriate-for-gestational-age (AGA) pregnancies. Methods: A total of 62 third-trimester human placentas were analyzed, including 47 from pregnancies complicated by FGR and 15 from pregnancies with AGA fetal growth. The mRNA expression of the IGF-1Eb isoform was assessed by reverse-transcription quantitative PCR in a subset of 28 fresh placental samples. IGF-1Eb protein immunoreactivity was assessed in paraffin-embedded tissue sections. Histopathological lesions were classified according to the Amsterdam criteria, and associations with clinical, demographic, and pathological parameters were evaluated using appropriate statistical analyses. Results: IGF-1Eb mRNA expression did not differ significantly between the FGR and AGA groups. In contrast, significant differences in IGF-1Eb immunoreactivity were observed in selected placental compartments. Moderate immunoreactivity in the perivillous syncytiotrophoblast was more frequent in FGR placentas and was associated with histological features of maternal vascular malperfusion, as well as with gestational age, neonatal birth weight, placental weight, maternal body mass index, and fetal sex. Increased IGF-1Eb immunopositivity was also observed in the endothelium of maternal decidual and fetal villous vessels in FGR placentas. No significant differences were observed in IGF-1Eb immunoreactivity in the extravillous trophoblast. Conclusions: In this observational study, placental IGF-1Eb protein immunoreactivity, but not mRNA expression, differed between FGR and AGA pregnancies in selected placental compartments. These findings indicate compartment-specific differences in IGF-1Eb protein immunoreactivity, associated with FGR and placental pathological features. However, the observational and cross-sectional design does not establish causality or a functional role for IGF-1Eb in placental dysfunction. Larger prospective studies incorporating functional validation are required to clarify the biological significance of these findings. Full article

Background: Opioid use during pregnancy is linked to preterm birth, fetal growth restriction, and Neonatal Opioid Withdrawal Syndrome. While the placenta is the primary regulator of the uterine environment, the precise molecular mechanisms by which opioids dismantle placental function remain poorly defined. Methods: The transcriptomic landscape of opioid-exposed human placentas from a unique Hawai’i-based cohort was characterized. Results: Transcriptional signatures were defined by genes involved in translational inhibition and metabolic attenuation. Integrative network modeling predicted a prominent stress-signaling hub centered on p38 Mitogen-Activated Protein Kinase and Extracellular Signal-Related Kinase 1/2, paralleling a broad suppression of ribosomal protein transcripts (Ribosomal Protein 27S, -29, and -39). This response was further characterized by the inhibition of the Myelecytomatosis Proto-Oncogene regulatory hub, predicting a loss of mitochondrial phosphate transport through associated genes (via Solute Carrier Family 25A3) and cell-cycle progression (via S-Phase Kinase-Associated Protein 1). Additionally, the genes in this model suggested upregulation of antisense regulatory brakes, such as RAP2C Antisense RNA 1, which might further reinforce this inhibitory state. Conclusion: The findings suggest that prenatal opioid exposure is associated with the disruption of placental homeostasis. This may be coordinated by protein synthesis and bioenergetic flux, as inferred from the modeled eukaryotic Translation Initiation Factor-mediated Integrated Stress Response. These findings establish a localized, clinical baseline of human placental stress, highlighting candidate molecular regulatory nodes to guide future mechanistic studies and biomarker discovery in exposed pregnancies. Full article