bims-placeb Biomed News
on Placental cell biology
Issue of 2025–07–27
sixteen papers selected by
Carlos M Guardia, National Institute of Health



  1. Birth Defects Res. 2025 Aug;117(8): e2514
       BACKGROUND: Dexamethasone (DEX) is used during pregnancies at risk of early delivery or congenital adrenal hyperplasia. DEX exposure is also known to cause placental damage. Although placental cytokines/chemokines protect the fetus and regulate placental development, few studies have examined placental cytokine/chemokine transcript levels in DEX-dosed pregnant mice.
    METHODS: To examine this, quantitative PCR and histological analysis in humanized mice were performed. Mice were injected once daily for five consecutive days with DEX (5 mg/kg) or saline (0.9%) via the tail vein on gestation days (GDs) 10-14, respectively (n = 3-5). All mice were intravenously injected with human immunoglobulin G (2 mg/kg) on GD14.
    RESULTS: No statistically significant changes in maternal body weights by GD 12, absolute or relative placental weights in the dosed group were observed compared to concurrent controls. Fetal weights in the DEX-dosed group were lower than in concurrent controls, and statistically significant changes were observed on GD 18. Necrosis/apoptosis of cytotrophoblasts in the placenta's labyrinth zone was observed in the DEX-dosed dams. The placental transcript levels of interferon lambda receptor 1, interleukin 6, and C-X-C motif chemokine ligand 10 (Cxcl10) were higher in the DEX-dosed than the control group on GDs 15 and 16; the difference of Cxcl10 transcript level was statistically significant (p = 0.016) on GD 16.
    CONCLUSIONS: Cxcl10 is overexpressed during DEX-induced placental damage in the mouse models, suggesting it as a potential biomarker of placental damage. Further studies are needed to confirm Cxcl10 changes during placental damage induced by other placental toxicants.
    Keywords:  chemokines; cytokines; dexamethasone; inflammation; mice; morphology; placenta; placental damage
    DOI:  https://doi.org/10.1002/bdr2.2514
  2. Exp Cell Res. 2025 Jul 22. pii: S0014-4827(25)00284-8. [Epub ahead of print] 114684
      Trophoblasts are epithelial cells critical for placental development and function, ensuring healthy fetal growth. We have previously isolated trophoblast stem cells (TSC) from first trimester placentae using the side-population technique, showing that they persist to term for the first time, and are depleted in fetal growth restriction (FGR) - a serious condition of pregnancy where placental exchange function is impaired. However, the functional role of TSC in pregnancy pathologies has not previously been directly examined. Here, we first demonstrate that third-trimester side-population trophoblasts represent a TSC population that can differentiate into mature trophoblast lineages in a similar manner to their first trimester counterparts, and then combine transcriptomic and functional studies to demonstrate deficits in proliferation, differentiation, and susceptibility to cell death in FGR. Together, such stem cell level defects may have profound impacts on all downstream trophoblast lineages, potentially explaining why placentation is impaired in FGR.
    Keywords:  Placenta; fetal growth restriction; side-population trophoblasts; trophoblast stem cells
    DOI:  https://doi.org/10.1016/j.yexcr.2025.114684
  3. J Assist Reprod Genet. 2025 Jul 23.
       BACKGROUND: The human placenta plays an important role in pregnancy and offspring health. The paternal genome contributes significantly to placental growth and development. While the maternal factors affecting gestational health are thoroughly investigated, the paternal factors are often overlooked. Thus, it is important to understand various paternal factors affecting placental development and function.
    OBJECTIVE: To assess the effect of various paternal factors on placental development, function, and pregnancy-related disorders.
    MATERIALS AND METHODS: This review was registered in PROSPERO (Registration number CRD420250634649). Literatures across databases like JSTOR, Scopus, Google Scholar, ScienceDirect, and PubMed were screened through a set of criteria. Forty-eight studies were selected that included low-to-moderate risk paternal factors like age, smoking, race/ethnicity/location, genetic, epigenetic factors, exposure to chemicals, seminal plasma, and lifestyle factors.
    RESULTS: Increased paternal age was reported to contribute towards higher risks of preeclampsia, spontaneous abortions, preterm birth, stillbirth, and higher placental and fetal birth weight. Paternal smoking, on the other hand, was found to be an associated risk factor for placental abruption and stillbirth. Exposure to various chemicals was found to be associated with changes in sperm epigenome and placental dysfunction.
    DISCUSSION AND CONCLUSIONS: Paternal health, lifestyle, and exposure to chemicals may affect placental development and pregnancy. Paternal factors may alter seminal plasma proteome, cytokine profile, and abnormal sperm DNA methylation of imprinted genes which is associated with adverse pregnancy outcomes. Pre-conceptional health assessment of prospective fathers might be helpful in ensuring optimal placental development in pregnancies to follow, in addition to newborn health.
    Keywords:  Epigenetic; Paternal factors; Placental development; Pre-term birth; Preeclampsia; Recurrent spontaneous abortions
    DOI:  https://doi.org/10.1007/s10815-025-03594-3
  4. Nat Commun. 2025 Jul 18. 16(1): 6614
      Preeclampsia (PE) and fetal growth restriction (FGR) complicate 5-10% of pregnancies and are major causes of maternal and fetal morbidity and mortality. Here we demonstrate that measuring circulating cell-free RNAs (cfRNAs) from maternal plasma can accurately predict pregnancies complicated by the combination of PE and FGR. We investigated 751 maternal plasma samples from 195 pregnant women (39 cases; 156 non-cases). We developed machine learning models from our discovery cohort (15 cases; 60 non-cases) and evaluated their predictive performances internally (24 cases; 96 controls) and externally (40 cases; 73 non-cases). We found circulating leptin (LEP) and pappalysin2 (PAPPA2) cfRNAs are the strongest cfRNA predictors of complicated pregnancies, each with an area under the receiver operating characteristic curve (AUC) of ~0.82. Using an external validation dataset of women with established PE, the combination of LEP and PAPPA2 had an AUC ~0.951. Our findings show that cfRNAs can predict complications of human pregnancy.
    DOI:  https://doi.org/10.1038/s41467-025-61931-7
  5. Curr Issues Mol Biol. 2025 Apr 11. pii: 271. [Epub ahead of print]47(4):
       BACKGROUND: This case-control study investigates whether miR-27a rs895819 A>G polymorphism is associated with an increased risk of recurrent pregnancy loss (RPL) in Caucasian Greek women.
    METHODS: This study included 93 women with at least two unexplained miscarriages before the 24th week of gestation (RPL group) and 107 women with no pregnancy loss history (control group). The miR-27a rs895819 A>G polymorphism was detected using PCR amplification, followed by DraIII-HF restriction enzyme digestion.
    RESULTS: The GG genotype was linked to a significantly higher risk of RPL (p-value = 0.00005), whereas the AA genotype was associated with a significantly lower risk (p-value = 0.00036). The AG genotype appeared more frequently in women with RPL (49.5% vs. 44.9% in controls), but the difference was not statistically significant (p-value = 0.5139).
    CONCLUSIONS: To our knowledge, this is the first study demonstrating that the miR-27a A>G polymorphism was significantly associated with a higher risk of recurrent miscarriage in Caucasian women. These findings provide evidence that the GG genotype may serve as a potential genetic marker for identifying women at higher risk of recurrent miscarriage, offering valuable insights for genetic counseling and reproductive medicine.
    Keywords:  infertility; miR-27a gene; miscarriage; recurrent pregnancy loss (RPL); rs895819 polymorphism
    DOI:  https://doi.org/10.3390/cimb47040271
  6. Placenta. 2025 Jul 14. pii: S0143-4004(25)00305-4. [Epub ahead of print]
      A growing body of evidence demonstrates that androgens play crucial roles in female reproductive physiology. Androgen receptor (AR) expression appears at all levels of the hypothalamic-pituitary-gonadal axis and other female reproductive organ or tissue such as uterus, placenta and immune system. Via AR-mediated mechanisms, androgens regulate key reproductive processes including follicular development, embryo implantation, placental formation, and pregnancy maintenance. AR knockout models suffer from considerable reproductive defects characterized by defective follicular development, reduced ovulation, decreased fertility, even premature ovarian failure. Clinically, low maternal serum testosterone correlates with diminished ovarian reserve and adverse pregnancy outcomes. These findings establish that a critical threshold of androgen is essential for successful pregnancy. While androgen excess has long been associated with follicular dysfunction and endometrial abnormalities leading to infertility and miscarriage, emerging evidence indicates that insufficient androgen similarly compromise female reproductive function. This review synthesizes fundamental discoveries and clinical evidence elucidating androgen's multifaceted effects on female reproduction. Collectively, we underscore the physiological significance of optimal androgen signaling and the pathological consequences from androgen deficiency across reproductive process.
    Keywords:  Androgen; Embryo; Follicle; Placenta; Pregnancy
    DOI:  https://doi.org/10.1016/j.placenta.2025.07.073
  7. Am J Reprod Immunol. 2025 Aug;94(2): e70130
       PROBLEM: The decidua is the interface between the uterus and the fetus. Studying decidual cells can reveal how healthy pregnancies are supported and mechanisms of pregnancy complications. There are two methods of obtaining decidual tissue following delivery. The placental bed can be suctioned following C-section deliveries, or a thin layer of decidual tissue can be dissected from the placenta. This study aimed to compare immune cell populations obtained using the two methods.
    METHOD OF STUDY: From individuals with scheduled C-sections, we collected peripheral blood, decidua via vacuum suction of the placental bed, and decidua via dissection of the uterine-facing side of the placenta. Samples were analyzed using a 22-color full-spectrum flow cytometry panel to identify immune cell subsets and functional markers.
    RESULTS: The cellular composition of both decidual tissue collection methods were more similar to each other than to peripheral blood. Decidua collected via vacuum suction (Suc. decidua) had more live CD45+ cells. Decidua collected via dissection of the uterine-facing side of the placenta (Plac. decidua) had significantly higher expression of Helios in CD4+ cells, suggesting more fetal T cells. Both types of decidual samples contained similar levels of Tr1-like regulatory T lymphocytes expressing LAG3 and CD49b, whereas peripheral blood did not have this cell type.
    CONCLUSION: Collecting decidual tissue using either method resulted in largely similar immune cell populations, suggesting studies are largely comparable regardless of whether samples were collected via suction or placental dissection. This will allow for greater flexibility in sample collection methods.
    Keywords:  decidua; flow cytometry; immune system; leukocytes; placenta
    DOI:  https://doi.org/10.1111/aji.70130
  8. J Neuroendocrinol. 2025 Jul 24. e70071
      Alcohol use remains common in pregnancy with prenatal alcohol exposure (PAE) associated with a plethora of adverse outcomes, including impaired emotional regulation and stress reactivity. Prior preclinical studies and emerging clinical evidence indicate that PAE affects the fetal hypothalamic-pituitary-adrenal (HPA) axis via the maternal-fetal interface in the placenta; however, little is known about the effect of these alterations on neurodevelopmental outcomes. We earlier reported on the effect of PAE and maternal stress on HPA axis biomarkers in placenta and umbilical cord (UC) blood; in the current study, we examined the effect of HPA axis biomarkers on infant neurodevelopmental outcomes at 6-9 months of term-equivalent age. Participants in the Ethanol, Neurodevelopment, Infant and Child Health (ENRICH-2) prospective cohort were followed from the second trimester of pregnancy until infants were 6-9 months of term-equivalent age. Maternal alcohol use was assessed through prospective interviews and a battery of ethanol biomarkers; maternal stress, by a Perceived Stress Scale (PSS). Placenta and UC blood specimens were collected shortly after birth, flash frozen, and analyzed for mRNA and protein expression of placental corticotropin-releasing hormone (pCRH), hydroxysteroid 11-beta dehydrogenase types 1 and 2 (HSD11B1, HSD11B2) and corresponding proteins (11β-HSD1 and 11β-HSD2), and Nuclear receptor subfamily 3 Group C Member 1-alpha (NR3C1-α) and corresponding glucocorticoid receptor alpha. UC plasma cortisol and cortisone levels were measured with ELISA. Bayley Scales of Infant Development, fourth edition (BSID-4; Motor, Language, Cognitive scores) and Infant Behavior Questionnaire Revised (IBQ-R; Surgency, Orienting/Regulation, Negative Affect) assessed neurodevelopment at 6-9 months of term-equivalent age. Pearson correlation was used to examine associations between placental HPA axis biomarkers and neurodevelopmental outcomes overall and after stratification by group (Alcohol/Control). Multivariable linear regression assessed the independent effect of placental biomarkers and Alcohol * biomarker interactions on infant outcomes after adjusting for Alcohol and maternal stress. Participants (32 Alcohol and 68 Controls) were comparable in sociodemographic characteristics. Activation of the placental HPA axis was correlated with a decrease in BSID-4 scores among Controls and an increase in IBQ-R scores (Surgency and Negative Affect) among Alcohol participants. In multivariable analyses, the HSD11B2/HSD11B1 ratio was associated with a decrease in Cognitive scores, and the Alcohol * pCRH interaction was associated with a decrease in Orienting/Regulation and an increase in Surgency and Negative Affect (all p's < .05), after adjusting for Alcohol and PSS. A significant independent effect of PSS was also observed on infant motor skills, Orienting/Regulation, and Negative Affect. This is the first clinical study to characterize the role of placental HPA axis biomarkers and maternal psychosocial stress in PAE-induced changes on infant neurodevelopment, highlighting the importance of a "placenta-brain axis". We demonstrated that the effects of mild-to-moderate PAE on infant neurobehavior were observed in participants with the highest quartile of pCRH expression, emphasizing the role of placental biomarkers in PAE-induced effects.
    Keywords:  HPA axis; infant stress regulation; placenta; pregnancy; prenatal alcohol exposure
    DOI:  https://doi.org/10.1111/jne.70071
  9. Curr Issues Mol Biol. 2025 May 20. pii: 375. [Epub ahead of print]47(5):
      The central role of angiotensinogen in the control of blood pressure is revealed by a series of crystallographic structures, including complexes with renin. Specifically, the structures provide an understanding of the sequential molecular events that lead to the pre-eclamptic hypertensive crises of pregnancy. The release of the precursor vasopressor peptide from the amino-terminal tail of angiotensinogen appears to be modulated by a redox-sensitive disulphide bridge. Our findings indicate that the activation of the thiol-switch in the circulating maternal angiotensinogen occurs at the placental level in response to oxidative stress, exacerbated by placental insufficiency. We propose here that a contributory factor is the inherent redox stress accompanying the placental exchange of oxygenation between the haemoglobin of the mother (oxy-HbA) and the deoxygenated haemoglobin of the foetus (deoxy-HbF).
    Keywords:  S-nitrosylation; angiotensinogen; hypertension; placenta redox stress; pre-eclampsia
    DOI:  https://doi.org/10.3390/cimb47050375
  10. Cureus. 2025 Jun;17(6): e86271
      Placenta accreta spectrum (PAS) refers to a group of disorders characterized by abnormal trophoblastic invasion of the uterine wall, which can result in life-threatening complications such as severe hemorrhage and the need for hysterectomy. A 30-year-old female patient with a history of two prior cesarean sections and diagnosed with Grade IV placenta previa at 34+0 weeks gestation was referred to our hospital for management. The patient presented with antepartum hemorrhage and was at elevated risk for PAS due to her previous cesarean sections and placenta previa. Ultrasound findings suggested PAS, including hypervascularity, consistent with trophoblastic invasion. Elective cesarean section was performed, and intraoperatively, focal accreta was identified with manual removal of the placenta and bilateral uterine artery ligation to control hemorrhage. Histopathology confirmed myometrial tissue with hemorrhage and dilated blood vessels, consistent with PAS, but without evidence of malignancy. The patient was managed in a multidisciplinary setting and received postoperative care for bleeding complications related to Factor 12 deficiency. Her recovery was uneventful, and she was discharged on postoperative day 3. This case highlights the importance of early diagnosis, imaging, and multidisciplinary management in optimizing maternal and fetal outcomes in PAS.
    Keywords:  antepartum hemorrhage; focal accreta; focal placenta accreta; placenta previa; previous cesarean section
    DOI:  https://doi.org/10.7759/cureus.86271
  11. J Reprod Immunol. 2025 Jul 16. pii: S0165-0378(25)00200-1. [Epub ahead of print]171 104622
      The placenta mediates fetal growth, and its development and function are influenced by immune interactions at the maternal-fetal interface. The cysteine-cysteine chemotactic cytokine receptor type 5 (CCR5) gene codes for a pro-inflammatory protein receptor expressed in the placenta on syncytiotrophoblasts and Hofbauer cells. Associations of the placental-fetal genotype at CCR5 and birth outcomes have not been examined. Furthermore, influence of CCR5 polymorphisms on nearby DNA methylation in the placenta and in the context of infection is understudied. We assessed two functional polymorphisms in CCR5, a 32 base pair deletion (Δ32) in the open reading frame and an A/G promoter point mutation (rs1799987) in EPIC (n = 233) a cohort consisting of complicated and uncomplicated pregnancies ascertained in Vancouver BC and found that the variant alleles were associated with birth weight (p = 0.007 and p = 0.01 respectively). We validated the association of rs1799987 with birthweight (p = 0.003) in the published NICHD dataset of normative term births (n = 286). These variant associations were, however, not present in CARMA-Preg (n = 200) a cohort enriched for HIV-exposure. Interestingly, we found rs1799987 was associated with altered DNA methylation (DNAme) at multiple CpGs spanning over 275 kb, overlapping both the CCR2 and CCR5 genes. DNAme in this region was, however, not associated with birthweight. Further investigations are needed to validate the association of CCR5 variants with fetal growth. Such studies must consider the population structure and demographics, as well as the large haplotype blocks spanning this region, which make it difficult to assign a causal relationship to specific variants.
    Keywords:  CCR5; Fetal growth restriction; Placenta; Preeclampsia
    DOI:  https://doi.org/10.1016/j.jri.2025.104622
  12. Nucleic Acids Res. 2025 Jul 19. pii: gkaf669. [Epub ahead of print]53(14):
      Peroxisome proliferator-activated receptor gamma (PPARG) is a nuclear receptor family transcription factor (TF) critical for adipogenesis, lipid metabolism, insulin sensitivity, and inflammation. It has also been known to play essential roles in trophoblast development and placentation. Dysregulation of PPARG in trophoblast differentiation has been implicated in pregnancy complications, such as pre-eclampsia and gestational diabetes. However, the molecular mechanisms of PPARG-dependent target gene regulation and its interactions with other regulatory factors during human trophoblast differentiation remain unclear. Using human trophoblast stem cells (TSCs), mimicking placental cytotrophoblasts (CTs), and their differentiation into extravillous trophoblasts (EVTs) as our models, we reveal that PPARG has cell-type-specific targets in TSCs and EVTs. We also find that while PPARG is essential for both TSC self-renewal and EVT differentiation, only its role in EVT differentiation is ligand sensitive and requires ligand-binding domain (LBD)-mediated transcriptional activity, whereas its function in TSC self-renewal appears to be ligand insensitive. Combined analysis with chromosomal targets of previously defined key TFs in TSCs and EVTs shows that PPARG forms trophoblast cell-type-specific regulatory circuitries, leading to differential target gene regulation via transcriptional re-wiring during EVT differentiation. Additionally, the enhanced invasiveness of EVTs treated with a PPARG agonist suggests a potential connection between PPARG pathways and human placenta accreta.
    DOI:  https://doi.org/10.1093/nar/gkaf669
  13. Placenta. 2025 Jul 18. pii: S0143-4004(25)00306-6. [Epub ahead of print]169 21-29
       OBJECTIVE: Hyperhomocysteinemia (HHcy), characterized by elevated homocysteine levels, is associated with adverse pregnancy outcomes, though its mechanistic link to placental dysfunction remains unclear. This study aimed to explore how HHcy disrupts placental development to identify conserved molecular mechanisms related to adverse pregnancy outcomes.
    METHODS: We develop murine HHcy model using a high-methionine diet and observe placental and fetal developmental outcome at key pregnancy times (E7.5, E10.5, E13.5). Structural and functional anomalies were detected histopathologically and molecularly to examine potential placental pathology. Expression profiles in placental tissues were determined by transcriptome profiling to describe dysregulated pathways. Expression and activity of lysosomal-autophagy were examined by qRT-PCR, western blotting, and transmission electron microscopy. Clinical validation was performed using placental samples from spontaneous abortion (SA) patients with HHcy and without HHcy and matched controls.
    RESULTS: HHcy-exposed mice exhibited significant reductions in embryo implantation rates and fetal viability, accompanied by impaired placental growth and structural disorganization. Histological analysis revealed atrophy of the ectoplacental cone, dilation of intervillous spaces, and diminished labyrinthine/junctional zones. Transcriptomic data highlighted enrichment of lysosomal and inflammatory pathways, corroborated by molecular evidence of lysosomal overload, suppressed autophagy-related gene expression and dysregulated autophagic flux. Placental samples from SA patients with HHcy mirrored these molecular alterations.
    CONCLUSION: Our findings suggest that HHcy disrupts placental homeostasis, impairs lysosomal function, and triggers maladaptive autophagy, leading to adverse pregnancy outcomes. The conserved pathways suggest targeting the lysosomal - autophagic axis might treat HHcy - related pregnancy problems.
    Keywords:  Autophagy; Lysosome; Placental development; hyperhomocysteinemia
    DOI:  https://doi.org/10.1016/j.placenta.2025.07.074
  14. Metabolites. 2025 Jun 24. pii: 431. [Epub ahead of print]15(7):
       BACKGROUND: Iron is an important micronutrient under physiological conditions, including pregnancy. On the other hand, excessive iron intake is also associated with adverse pregnancy outcomes. Macrophages are crucial in regulating iron homeostasis and pregnancy conditions. However, the role of macrophages in iron metabolism during pregnancy is unclear. Therefore, we used mouse models to investigate whether maternal iron overload induces pregnancy complications and their interactions with macrophages.
    METHODS AND RESULTS: Administration of high-dose iron (iron dextran) by intraperitoneal injection to pregnant mice induced pregnancy complications such as fetal death, but low-dose iron did not affect fetal weight. In the placenta, the amount of iron was significantly increased and levels of macrophages were decreased by iron administration. In the liver, iron administration dramatically increased the amount of iron, with increased inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-6. Macrophages were observed to surround deposited iron in the liver. In an in vitro experiment, treatment with iron stimulated TNFα secretion with cell death in macrophages, but not in liver cells. To investigate the importance of macrophages during pregnancy, clodronate liposomes were administered to reduce macrophages in pregnant mice. The macrophage reduction in pregnant mice resulted in an increased absorption rate and fetal growth restriction, together with higher iron accumulation and inflammatory cytokines in the liver.
    CONCLUSIONS: Maternal excess iron may induce inflammatory conditions with macrophage dysfunction in the liver, resulting in pregnancy complications. The reduction in macrophages also induced higher iron levels and adverse effects during pregnancy, suggesting a vicious cycle between excessive iron and macrophage dysfunction during pregnancy.
    Keywords:  inflammation; iron; liver; macrophages; placenta; pregnancy complication
    DOI:  https://doi.org/10.3390/metabo15070431
  15. Placenta. 2025 Jul 16. pii: S0143-4004(25)00310-8. [Epub ahead of print]169 39-48
       INTRODUCTION: Uterine contractile activity, essential for vaginal birth, begins early in gestation, but quantitative assessment remains limited. T2∗ relaxometry detects placental oxygenation changes during contractions, offering insights into placental function. This study uses a large dynamic T2∗ MRI database and an AI-driven pipeline to assess contractile activity, quantify prevalence, and explore links with clinical and scanning variables. By leveraging real-time deep learning, it aims to enhance understanding of subclinical contractions and their impact on placental function and antenatal care.
    METHODS: A total of 821 dynamic fetal MRI scans were analyzed from pregnancies between 15 and 41 weeks of gestation, including both uncomplicated pregnancies and those affected by placental insufficiency. An automated pipeline incorporating deep-learning-based placental and fetal brain segmentation, as well as dynamic signal analysis, was used to evaluate uterine contractility.
    RESULTS: Contractile activity was detected in 19 % of cases, showing no significant correlation with field strength, maternal position during the scan, parity, maternal age, or body mass index. However, activity increased with advancing gestational age, peaking notably in the week before delivery. The observed variations in T2∗ values between contractile states underscore the importance of accounting for dynamic uterine activity in placental MRI analysis.
    DISCUSSION: Dynamic T2∗ MRI assessment of uterine contractility provides novel insights into subclinical uterine contractions and establishes a foundation for real-time detection in the future. This approach could significantly enhance our in vivo understanding of placental function during contractions, particularly in pregnancies affected by placental disease, ultimately improving prenatal monitoring and clinical management.
    Keywords:  Fetal MRI; Placental function; T2∗ relaxometry; Uterine contractions
    DOI:  https://doi.org/10.1016/j.placenta.2025.07.078
  16. BMC Pregnancy Childbirth. 2025 Jul 24. 25(1): 786
       BACKGROUND: Pre-eclampsia continues to be a significant global health burden with complex pathophysiology, necessitating investigation of novel biomarkers to improve understanding, diagnosis and management of this pregnancy-specific disorder.To investigate the differential expression of Calcium Release-Activated Calcium Channel Protein 1 (ORAI1), Fibroblast Growth Factor 23 (FGF23), Placental Protein 13 (PP13), Palladin, and Supervillin in both maternal and umbilical cord blood as potential biomarkers for late-onset pre-eclampsia.
    METHODS: This cross-sectional, case-control study included 61 women with late-onset pre-eclampsia and 61 normotensive pregnant women undergoing cesarean delivery. Maternal blood samples were collected immediately prior to cesarean delivery, and umbilical cord blood was obtained immediately after delivery of the placenta. Protein concentrations in both circulatory compartments were measured using enzyme-linked immunosorbent assay. The unique study design with paired maternal-cord blood sampling provided insights into maternal-fetal protein transfer dynamics in pre-eclamptic conditions.
    RESULTS: Maternal and cord blood ORAI1 concentrations were significantly elevated in pre-eclampsia (p = 0.001 and p = 0.035, respectively), while FGF23 and PP13 were significantly decreased in maternal blood (p = 0.022 and p = 0.018, respectively). Maternal-to-cord blood concentration ratios for ORAI1 and FGF23 were significantly altered in pre-eclampsia (p = 0.038 and p = 0.021, respectively). ORAI1 showed the highest diagnostic accuracy (AUC = 0.733) and correlated positively with disease severity and negatively with birth weight. Combined ORAI1 and FGF23 assessment significantly enhanced diagnostic performance (AUC = 0.782).
    CONCLUSION: The altered expression of ORAI1, FGF23, and PP13 in late-onset pre-eclampsia suggests disruptions in calcium signaling, phosphate metabolism, and placental function. The parallel measurement of these proteins in both maternal and cord blood provided unique insights into maternal-fetal interface dysfunction in pre-eclampsia. The superior performance of combined ORAI1 and FGF23 measurement underscores the value of a multi-marker approach in capturing pre-eclampsia's complex pathophysiology, potentially contributing to improved diagnostic strategies and therapeutic interventions.
    Keywords:  FGF23; ORAI1; PP13; Palladin; Pre-eclampsia; Supervillin
    DOI:  https://doi.org/10.1186/s12884-025-07890-9