bims-placeb Biomed News
on Placental cell biology
Issue of 2026–08–02
ten papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences



  1. Am J Physiol Cell Physiol. 2026 Aug 01.
      Maternal obesity (MO) alters the intrauterine environment and increases the risk of a variety of developmental outcomes; however, the effects on placental cell population and development remain unclear. In this study, we investigated the impact of MO on placental cellular composition, development, and morphology in C57BL/6J mice fed a control or high-fat diet. Single-cell RNA sequencing of embryonic day (E) 13.5 placentas identified 16 transcriptionally distinct cell populations and revealed a reduction in the trophoblast progenitor cell population in MO placentas. MO suppressed trophoblast genes involved in placental development and mitochondrial oxidative phosphorylation, accompanied by decreased protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a key regulator of mitochondrial biogenesis. Furthermore, MO reduced the expression of Hand1 and Tfap2c, transcription factors involved in trophoblast differentiation and placental development, while increasing prolactin-family gene expression and STAT5 phosphorylation. At E17.5, MO caused female-specific reductions in placental weight and labyrinth zone area, along with increased Tnf expression and sustained suppression of Hand1 in female placentas. These findings suggest that MO disrupts trophoblast differentiation and placental metabolic function during midgestation, which may contribute to placental vulnerability later in pregnancy.
    Keywords:  maternal obesity; oxidative metabolism; placenta; prolactin; trophoblast
    DOI:  https://doi.org/10.1152/ajpcell.00357.2026
  2. Arch Physiol Biochem. 2026 Jul 30. 1-15
      Background: In early pregnancy, trophoblast invasion and uterine vascular remodelling must be tightly regulated to ensure maternal-foetal circulation. Inhibition of these processes causes preeclampsia, foetal development retardation, and recurrent pregnancy loss. It is unclear whether molecular regulators control trophoblast invasiveness and uterine vascular adaption, despite much investigation. Methods: Here, a Protein-Mediated Vascular Remodelling Enhancement (PM-VRE) technique is proposed to examine trophoblast invasion mediated by particular regulatory proteins by increasing uterine vascular remodelling. Protein expression profiling and pathway interaction analysis comprise PM-VRE. Results: Experiments show protein signalling drives endothelial transformation, artery remodelling, and trophoblast migration, with upregulated angiogenic and matrix pathways enabling vascular adaptation. It achieves higher trophoblast invasion depths (∼195-210 µm), enhanced endothelial responsiveness (up to 95%), increased ECM remodelling activity (∼75-80), greater vascular resistance reduction (∼78%), and improved placental perfusion stability (up to 90). Conclusion: PM-VRE provides an effective framework for identifying molecular regulators of trophoblast invasion and uterine vascular remodeling, offering insights into mechanisms underlying placental development and pregnancy disorders associated with impaired placentation.
    Keywords:  Trophoblast invasion; angiogenesis; placentation; pregnancy complications; protein-mediated signalling; uterine vascular remodelling
    DOI:  https://doi.org/10.1080/13813455.2026.2699136
  3. Front Public Health. 2026 ;14 1863387
      Early-onset preeclampsia (EOPE) remains a leading cause of maternal and perinatal morbidity worldwide. This review synthesizes evidence that premature placental senescence, centered on syncytiotrophoblast stress and the senescence-associated secretory phenotype (SASP), provides a mechanistic framework connecting placental injury to the maternal syndrome. In EOPE, defective spiral artery remodeling (45) and repeated ischemia-reperfusion can promote oxidative damage, persistent DNA-damage responses, impaired autophagy, and durable cell-cycle arrest in trophoblast lineages. Convergent data show elevated senescence markers (p16INK4a, p21, SA-β-galactosidase, γ-H2AX), transcriptomic signatures consistent with placental SASP programs, and senescent syncytiotrophoblast secretion-PAI-1 (~4-fold) and activin A (~2-fold). The SASP can transform the placenta into a source of cytokines, antiangiogenic factors, cell-free nucleic acids, and extracellular vesicles that may bias the maternal circulation toward endothelial dysfunction. We propose a stage-based model of EOPE progression and discuss differences from late-onset disease. Senescence-linked circulating signals may support multimarker risk stratification and liquid-biopsy strategies. We emphasize that human causal evidence remains associative and the senescence model is best regarded as a testable framework complementing established immune, complement, and angiogenic models.
    Keywords:  SASP; early-onset preeclampsia; endothelial dysfunction; extracellular vesicles; liquid biopsy; placental senescence; syncytiotrophoblast
    DOI:  https://doi.org/10.3389/fpubh.2026.1863387
  4. Biol Reprod. 2026 Jul 31. pii: ioag166. [Epub ahead of print]
      Over the first trimester, vasculogenesis (the de novo formation of blood vessels) and angiogenesis (creation of new vessels from existing vessels) together create the backbone of the placental vascular network, which becomes increasingly complex as gestation progresses to term. Many different ex vivo imaging modalities, including computed tomography, synchrotron X-ray tomography, confocal and electron microscopy, and traditional histology and stereology, have been used to study the vascularity of the human placenta in detail. However, many of these techniques often come with trade-offs between resolution, maximum sample size and cost. Light sheet fluorescence microscopy is an attractive method capable of imaging placental 3D morphology at the micro-scale, whilst also enabling imaging of comparatively larger placental explants than other microscopy techniques, allowing capture of more generations of villous and vascular trees. Advances in tissue clearing for optical imaging have led to a multitude of different published light sheet fluorescence microscopy protocols across tissue types. However, optimising placenta-specific protocols is imperative for high-quality imaging and downstream three-dimensional analysis of this unique tissue. Finally, the placental vascular architecture is notoriously disorganised, heterogenous and convoluted, making it more challenging to segment and obtain meaningful data than from vasculature in other organ systems. Here, we present a comprehensive pipeline for placental tissue preparation, light sheet fluorescence imaging and image segmentation of first trimester and term human placental villous explants, enabling physiologically relevant quantitative analysis of vascularity at different stages of gestation.
    Keywords:  Feto-placental Circulation; Light Sheet Fluorescence Microscopy; Placenta; Placental Vasculature
    DOI:  https://doi.org/10.1093/biolre/ioag166
  5. Tissue Eng Part A. 2026 Jul 29. 19373341261473156
      Trophoblast invasion into the decidualized endometrium is an important aspect of blastocyst implantation necessary for a successful pregnancy. There are many processes involving the early implantation and invasion of trophoblast cells into the maternal decidua that are not well described. Here, we describe the development of a microfluidic model of the trophoblast-endometrial interface that can be used to quantify metrics of trophoblast cell invasion, endothelial cell motility, and the influence of decidualization hormones on these processes.
    Keywords:  maternal–fetal interface; microfluidics; pregnancy; trophoblast invasion
    DOI:  https://doi.org/10.1177/19373341261473156
  6. Sci Rep. 2026 Jul 28. pii: 21820. [Epub ahead of print]16(1):
      The Mediterranean diet is associated with reduced cardiometabolic risk, yet its physiological effects during pregnancy and its impact on placental metabolism remain incompletely understood. This study aimed to determine whether maternal adherence to a Mediterranean diet during pregnancy influences placental lipid metabolism and signalling pathways involved in nutrient handling, tissue remodelling, and inflammation, and to assess their relationship with pregnancy outcomes. Placental samples and clinical outcome data were analysed from pregnant women participating in an unblinded randomized clinical trial of a Mediterranean diet intervention. Placental fatty acid composition was quantified, and the expression of genes and signalling pathways involved in lipid metabolism, nutrient transport, inflammation, and tissue remodelling was evaluated. Maternal adherence to a Mediterranean diet during pregnancy was associated with significant alterations in placental fatty acid composition, including reduced C18:0 and C24:0 and increased C18:1n9c, C20:3n6, and C22:0, with lower total saturated fatty acids and higher monounsaturated fatty acids. Placental expression of lipid metabolism regulators ALOX15 and PPARγ was reduced, alongside downregulation of AKT and p38 MAPK signalling pathways. Placentas from mothers adhering to the Mediterranean diet also showed lower expression of amino acid and glucose transporters SLC3A2 and SLC2A1, as well as altered inflammatory and extracellular matrix remodelling markers, including decreased SOCS3 and GHR and increased PAI1 and MMP3. Maternal adherence to a Mediterranean diet during pregnancy modifies placental fatty acid composition and regulates pathways involved in lipid handling, nutrient transport, inflammation, and tissue remodelling, providing insight into mechanisms linking maternal diet with placental metabolic function.
    Keywords:  Diet; Mediterranean diet; Metabolism; Placenta; Pregnancy
    DOI:  https://doi.org/10.1038/s41598-026-60877-0
  7. bioRxiv. 2026 Jul 13. pii: 2026.07.10.737757. [Epub ahead of print]
      Embryo culture, a required step during in vitro fertilization (IVF), exposes developing embryos to altered environmental conditions not normally experienced in vivo , including altered oxygen (O 2 ) tension. Importantly, O 2 influences gene expression, metabolism, and the activity of enzymes that sculpt the epigenetic landscape. The lowest O 2 tension currently used in clinics during embryo culture is 5%, despite evidence that sections of the mammalian female reproductive tract have O 2 levels as low at 2%. Lower O 2 may therefore better mimic the in vivo environment and thus lead to improved pre- and postnatal outcomes in IVF-conceived offspring. Using our validated IVF mouse model, we show embryo culture at 2% O 2 compared to culture under 5% O 2 significantly improves embryo cell number, the chromatin landscape in preimplantation embryos, fetal and placental development during gestation, and metabolic function in adulthood. We further uncover mechanisms by which culture under ultra-low O 2 mediates these improvements. Overall, these results suggest embryo culture with 2% O 2 ameliorates adverse outcomes after IVF and provide evidence that IVF could be further improved by adjusting culture conditions to model the in vivo environment.
    DOI:  https://doi.org/10.64898/2026.07.10.737757
  8. Front Public Health. 2026 ;14 1892134
      Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) represents a critical developmental concern because several PFAS cross the placenta and may perturb biological programming during sensitive windows. Although epidemiological and experimental studies have linked prenatal exposure to several measured PFAS, primarily legacy perfluoroalkyl acids such as perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), Perfluorohexane Sulfonic Acid (PFHxS), and Perfluorononanoic Acid (PFNA), to diverse offspring outcomes, the strength of evidence differs substantially across compounds and health domains. Current human evidence is strongest for impaired vaccine antibody responses and altered growth or metabolic trajectories in studies dominated by legacy PFAS, whereas evidence for other congeners, short-chain PFAS, ether-based alternatives, and fluorotelomer compounds remains sparse. Mechanistically, placental transfer, nuclear receptor perturbation, thyroid hormone transport disruption, mitochondrial stress, immune modulation, and epigenetic reprogramming may jointly contribute to developmental susceptibility. We further discuss how emerging PFAS alternatives and real-world mixture exposures challenge single-chemical and adult-centered assessment paradigms. Finally, we outline a conceptual framework for developmental hazard assessment, in which exposure-window characterization, congener-specific toxicokinetics, human-relevant models, multi-omics biomarkers, and PBPK/PBTK modeling are positioned as complementary components rather than as a fully operational assessment system.
    Keywords:  epigenetic programming; offspring health; per- and polyfluoroalkyl substances; placental transfer; prenatal exposure
    DOI:  https://doi.org/10.3389/fpubh.2026.1892134
  9. Anim Reprod. 2026 ;23(4): e20260067
      Seasonal heat stress (HS) is a pervasive environmental challenge with profound consequences for female reproductive physiology, affecting ovarian function, oocyte maturation, and early embryonic development. At the ovarian level, HS disrupts follicular growth, impairs steroidogenesis, and compromises granulosa cell function, thereby creating a suboptimal microenvironment that reduces oocyte competence. In oocytes, HS induces oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, spindle abnormalities, chromosomal missegregation, and persistent epigenetic alterations. These disruptions extend into early embryonic development, where redox imbalance, apoptosis, ER stress, and altered lineage allocation reduce cleavage and blastocyst formation, compromise trophectoderm and inner cell mass integrity, and impair implantation potential. Maternal heat exposure further exacerbates embryonic vulnerability by altering the oviductal and uterine environment, reducing embryotrophic factors and antioxidant defenses, and ultimately influencing offspring phenotype and fertility, potentially across generations. Accordingly, this review aims to synthesize current knowledge on the physiological and molecular impacts of heat stress on ovarian function, oocyte maturation, and early embryonic development. To this end, we consider studies conducted under both in vivo and in vitro conditions, highlighting shared and distinct mechanisms of thermal stress at the organ and cellular levels to identify potential targets for intervention.
    Keywords:  heat stress; oocyte and embryo; ovary; reproduction
    DOI:  https://doi.org/10.1590/1984-3143-AR2026-0067
  10. Pediatr Dev Pathol. 2026 Jul 31. 10935266261470991
       BACKGROUND: Determining placental functional capacity from a typical pathology report can be difficult. Our goal was to create a new way to report on the functional capacity of the placenta, using much of the typical information obtained in a routine placental pathology assessment.
    METHODS: Placental functional capacity score (PFCS), a continuous variable between 0 and 100, was defined by a combination of placental weight compared to that expected for gestational age, villous maturational abnormalities, percentage of parenchymal lesions, and presence of inflammation. We compared PFCS distributions in 3 existing placental pathology repositories, 2 with livebirths (n = 9783 and n = 575) and 1 with stillbirths (n = 149). Within the 2 livebirth cohorts, we compared PFCS by adverse pregnancy outcomes. Data were analyzed using SPSS and RStudio.
    RESULTS: PFCS could be robustly applied in the 3 cohorts and could be calculated using simple formulas easily applied by software programs. Mean PFCS was 74.60 (SD 18.09) and 77.23 (SD 16.56) in the 2 liveborn cohorts, but was markedly reduced to 62.61 (SD 28.92) in the stillbirth cohort (p<.0001). Mean PFCS was significantly lower in preterm birth compared to term births, SGA infant versus non-SGA infant, and preeclampsia versus no preeclampsia, in both of the liveborn cohorts.
    CONCLUSION: It is feasible to calculate a continuous, quantitative PFCS from information collected in routine placental pathology examination, and PFCS is reduced in stillbirths compared to live birth, in preterm births compared to term births, and in SGA infants compared to non-SGA infants.
    Keywords:  fetal vascular malperfusion; infarction; maternal vascular malperfusion; placental pathology; placental weight; quantitative scoring
    DOI:  https://doi.org/10.1177/10935266261470991