bims-placeb 2026-04-26 papers

bims-placeb

Biomed News

on Placental cell biology

Issue of 2026–04–26
fourteen papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences

Investigating human pregnancy with trophoblast organoids.
Placental immunodynamics regulated by leukocytes and trophoblasts: From pregnancy to onco-fetal immunity.
Investigating the impact of hypoxia and syncytialization on lipid nanoparticle-mediated mRNA delivery to placental cells.
MCT1-mediated bidirectional propionate transport across human placental syncytiotrophoblast layer: insights from a trophoblast stem cell-derived barrier model.
PLAC1 possesses fundamental and unique roles in regulating rat and human trophoblast cell development.
A Tubular 3D In Vitro Model of Placental Trophoblasts for Transport Studies.
PIP2 Accumulation in the Spongiotrophoblast Drives Trophoblast Apoptosis in Intrahepatic Cholestasis of Pregnancy.
CX3CR1 regulates the immune microenvironment in the placenta.
Dissecting placental host-pathogen interactions: Rift Valley fever virus infection in early human trophoblast stem cells.
Physiological and anatomical determinants of placental drug transfer.
Egfl7 regulates embryonic angiogenesis and placental vascular function in mice.
Placental handling of glucose in the human - beyond the maternal-fetal glucose gradient.
Lipoic acid attenuated hypoxia-induced disruption of mitochondrial respiration in an in vitro human trophoblast model.
High-Fat Diet Induces Preeclampsia-Like Phenotypes Associated with Impaired Decidualization and NF-κB Activation.

FEBS Lett. 2026 Apr 24.

Investigating human pregnancy with trophoblast organoids.

Ida Calvi, Margherita Yayoi Turco.

  The placenta plays a vital role in supporting and nourishing the fetus throughout pregnancy, yet the mechanisms governing its development remain poorly understood. Recent advances in 3D human trophoblast organoid systems derived from both primary tissues and stem cells provide physiologically relevant platforms to investigate placental development in both health and disease. This 'In a Nutshell' review highlights how these models are transforming our ability to investigate human placental biology in pregnancy.

Keywords:  development; maternal–fetal interactions; organoids; placenta; pregnancy; reproduction; trophoblast

DOI:  https://doi.org/10.1002/1873-3468.70344
J Reprod Immunol. 2026 Apr 17. pii: S0165-0378(26)00062-8. [Epub ahead of print]175 104893

Placental immunodynamics regulated by leukocytes and trophoblasts: From pregnancy to onco-fetal immunity.

Yao Wang, Ruqun Zheng, Jacqueline Pui Wah Chung, Chi Chiu Wang.

  The placenta is a pivotal organ in pregnancy, sustaining fetal development through nutrient exchange and immunological modulation. At the maternal-fetal interface (MFI), specialized maternal immune cells within the decidua closely interact with invading trophoblasts, orchestrating a finely tuned balance between immune tolerance and activation that supports successful pregnancy outcomes. In early pregnancy, decidual immune cells are integral to trophoblast invasion and spiral artery remodeling. Subsequently, they transition to a more immunomodulatory state that promotes immune tolerance in later gestation. Perturbations in this equilibrium, including altered cell subsets or aberrant activation, are increasingly associated with adverse pregnancy complications. Meanwhile, trophoblasts express an array of immune checkpoint molecules that further modulate the immunological landscape at the MFI. This review synthesizes recent advances in immune cell dynamics at the MFI in healthy pregnancy and gestational pathologies. We also emphasize the immunoregulatory and endocrine functions of trophoblasts in orchestrating maternal-fetal tolerance. Moreover, we highlight emerging parallels in immune regulation between placental and tumor immune microenvironments, providing insights into onco-fetal immunity and suggesting broader implications of placental immunology from pregnancy to cancer immunity.

Keywords:  Gestational complications; Maternal-fetal interface; NK cells; Onco-fetal immunity; Placental immunoregulation; Trophoblast

DOI:  https://doi.org/10.1016/j.jri.2026.104893
Bioeng Transl Med. 2026 Mar;11(2): e70114

Investigating the impact of hypoxia and syncytialization on lipid nanoparticle-mediated mRNA delivery to placental cells.

Rachel E Young, Tara Vijayakumar, Logan J Reilley, Krisha Darji, Diya Patel, Samuel Hofbauer, Mohamad-Gabriel Alameh, Drew Weissman, Rachel Riley.

  Placental dysfunction leads to pregnancy-related disorders that affect up to 15% of pregnancies. Several of these, such as preeclampsia, are symptomatically managed but have no curative treatments other than preterm delivery. Placental dysfunction arises from improper placental development, leading to restricted blood vessel formation and a hypoxic placental microenvironment. The development of placental therapeutics is challenging due to the complex physiology that enables the placenta to control uptake and transport. Here, we use a simple culture system that combines hypoxia and trophoblast syncytialization to model the functional syncytiotrophoblast layer of the placenta under hypoxic stress. Using this model, we evaluate the impact of hypoxia on lipid nanoparticle (LNP)-mediated mRNA delivery. Our data show that hypoxia hinders syncytiotrophoblast formation in vitro. Despite this, LNP delivery to syncytiotrophoblasts increases protein translation and secretion, particularly under hypoxic conditions. Further, we show delivery of a therapeutic mRNA, placental growth factor (PlGF), to syncytiotrophoblasts in hypoxia, which restored diminished PlGF levels back to normoxic controls. These findings provide an LNP platform for efficient mRNA delivery to hypoxic trophoblasts and demonstrate the importance of considering hypoxia towards the development of drug delivery platforms for placental therapeutics.

Keywords:  drug delivery; hypoxia; lipid nanoparticles; nucleic acids; preeclampsia; pregnancy; trophoblasts

DOI:  https://doi.org/10.1002/btm2.70114
J Physiol. 2026 Apr 24.

MCT1-mediated bidirectional propionate transport across human placental syncytiotrophoblast layer: insights from a trophoblast stem cell-derived barrier model.

Toshiaki Tsuchitani, Rin Midorikawa, Akari Kasuya, Saki Noguchi, Kohei Yamamoto, Tomohiro Nishimura, Hirokazu Kaji, Takeshi Hori, Masatoshi Tomi.

  Propionate, a gut microbiota-derived short-chain fatty acid, influences fetal development and postnatal metabolic programming. Although the fetus lacks microbiota and endogenous propionate production, human pregnancies show a fetal-to-maternal propionate concentration ratio greater than unity, suggesting concentrative transport across the placenta. However, its underlying mechanism remains undefined. The present study aimed to identify the transporter responsible for transplacental transport of propionate across the syncytiotrophoblast (SynT) layer. Transporter knockdown in human choriocarcinoma JEG-3 cells revealed that MCT1 (SLC16A1) silencing reduced [3H]propionate uptake, whereas knockdown of other anion transporters had no effect. Functional assays using Xenopus oocytes demonstrated that the expression of human MCT1, but not MCT4 (SLC16A3), increased [3H]propionate transport. In human trophoblast stem cell (hTSC)-derived SynT, [3H]propionate uptake was pH-dependent and significantly inhibited by MCT1-selective inhibitors. Subsequently, to evaluate transcellular transport, we performed quantitative permeability assays using a hTSC-derived placental barrier model. [3H]Propionate permeability was significantly higher than that of [14C]d-mannitol, a paracellular marker. MCT1 inhibition reduced [3H]propionate permeability in both apical-to-basal and opposite directions, whereas MCT4 inhibition had minimal effects. Notably, the hTSC-derived model exhibited a directional bias in [3H]propionate transfer, reflecting the fetal-directed enrichment observed in vivo. Mathematical model analysis further indicated that MCT1 functions at both the apical and basal membranes to facilitate bidirectional transport of propionate. Together, these findings identify MCT1 as the predominant mediator of propionate transfer across the human SynT layer, providing mechanistic insights into how the placenta governs fetal exposure to maternal microbiota-derived metabolites. KEY POINTS: The fetus relies on maternal-derived propionate for development, but the molecular mechanism responsible for its concentrative transport across the human placenta remains undefined. Using multiple human trophoblast models and functional expression assays, we identified MCT1, but not MCT4, as the primary mediator of propionate transport. A human trophoblast stem cell-derived placental barrier model successfully exhibited a directional bias in propionate transfer, reflecting the fetal-directed enrichment observed in vivo. Mathematical modelling of the permeability data from the human trophoblast stem cell-derived barrier model indicates that MCT1 functions at both the apical and basal membranes of the syncytiotrophoblast to facilitate bidirectional transport. These findings establish MCT1 as a key gateway for transplacental propionate transfer, providing mechanistic insights into how the placenta regulates fetal exposure to maternal microbiota-derived metabolites.

Keywords:  maternal–fetal transfer; monocarboxylate transporter 1; placenta; propionate; short‐chain fatty acids; trophoblast stem cells

DOI:  https://doi.org/10.1113/JP289595
Development. 2026 Apr 20. pii: dev.205290. [Epub ahead of print]

PLAC1 possesses fundamental and unique roles in regulating rat and human trophoblast cell development.

Ayelen Moreno-Irusta, Jovana Urosevic, Khursheed Iqbal, Arun S Seetharam, Jackson Nteeba, Regan L Scott, Marija Kuna, Masanaga Muto, Keisuke Kozai, Andjelka Celic, Hiroaki Okae, Takahiro Arima, David K Johnson, Geetu Tuteja, Michael J Soares.

  Placenta enriched 1 (PLAC1) is a conserved X chromosome-linked gene expressed in the mammalian placenta. We investigated the biology of PLAC1 in the rat and human placenta. Plac1 transcripts were expressed in the junctional zone of the rat placenta and in intrauterine invasive trophoblast cells. Genome-edited Plac1 mutant animals exhibited placentomegaly. Enlarged placentas were characterized by an expanded junctional zone, an irregular junctional zone-labyrinth zone boundary, a deficiency of intrauterine invasive trophoblast cells, and a late gestation stage uterine-placental interface infiltrated with natural killer cells. PLAC1 facilitated rat trophoblast cell differentiation. In contrast, PLAC1 showed minimal contributions to the regulation of the human invasive/extravillous trophoblast cell lineage, but instead PLAC1 expression and actions were linked to syncytiotrophoblast differentiation. Furthermore, PLAC1 impacts on cellular function were linked to furin, paired basic amino acid cleaving enzyme (FURIN), in rat and human trophoblast cells. Thus, PLAC1 is critically involved in hemochorial placentation; however, the responsive trophoblast cell lineages and its contributions to placentation are fundamentally distinct in the rat versus human.

Keywords:  FURIN; PLAC1; Placenta; Trophoblast cells

DOI:  https://doi.org/10.1242/dev.205290
ACS Biomater Sci Eng. 2026 Apr 21.

A Tubular 3D In Vitro Model of Placental Trophoblasts for Transport Studies.

Seyedaydin Jalali, Sandeep Raha, Ponnambalam Ravi Selvaganapathy.

  Successful pregnancy outcomes largely depend on the functional integrity of the placental barrier, which serves as a crucial interface between the maternal and fetal bloodstreams. Accurate modeling of the placental barrier is essential for understanding its physiological processes, developing therapeutics, and conducting transport studies for drug discovery and development that could have averted clinical disasters such as thalidomide-induced teratogenesis. Current models often fail to mimic the placental barrier's complex multilayer structure and consistently form nonleaky barriers due to traditional cell-seeding techniques and the inability to replicate the intricate architecture of the placental barrier. To our knowledge, a true 3D model that recapitulates the multilayer structure, mimics the syncytiotrophoblast layer with high confluency, facilitates cell-extracellular matrix interactions, and supports transport studies under dynamic conditions has not been previously reported. Here, we utilize the self-assembly process of BeWo placental trophoblastic cells and collagen I, a major component of the placental extracellular matrix, to create 3D tubular constructs. These constructs represent a significant advancement in the fabrication of physiologically relevant placental barrier models, enabling the modeling of the syncytiotrophoblast layer with underlying supportive cytotrophoblast layers and allowing for transport studies under dynamic conditions. Fluorescence imaging confirmed syncytial fusion and the formation of a continuous barrier. Permeability tests demonstrated that our model closely mirrors the in vivo transport properties of the placental barrier, highlighting the dominant role of the syncytiotrophoblast layer in governing the placental barrier transport. These models can be utilized for further transport studies, drug development and delivery, and placental barrier tissue engineering.

Keywords:  3D tubular constructs; BeWo; cellular migration; collagen; placental barrier; self-assembly; transport; trophoblast

DOI:  https://doi.org/10.1021/acsbiomaterials.5c02162
Mol Reprod Dev. 2026 Apr;93(4): e70105

PIP2 Accumulation in the Spongiotrophoblast Drives Trophoblast Apoptosis in Intrahepatic Cholestasis of Pregnancy.

Zhou-Tian Xu, Lu-Xing Ge, Li Luo, Hong-Ying Ma, Hong Xiao, Yu-Bin Ding.

  Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by elevated maternal bile acids and an increased risk of adverse fetal outcomes. Although placental dysfunction is a key contributor to ICP pathogenesis, the underlying mechanisms remain incompletely understood. Here, we combined a Sprague-Dawley rat model of ICP with spatial metabolomics to delineate region-specific metabolic alterations within the placenta. Multivariate analysis revealed distinct metabolic signatures between ICP and control placentas, with pronounced reprogramming in trophoblast-enriched regions. Differential metabolite and pathway analyses identified significant perturbations in glycerophospholipid metabolism, pyruvate metabolism, phospholipase D signaling, and the tricarboxylic acid cycle. Notably, phosphatidic acid (PA) was broadly elevated, whereas its downstream product phosphatidylinositol 4,5-bisphosphate (PIP2) exhibited spatially restricted accumulation in trophoblasts. Mechanistically, taurocholic acid exposure in HTR-8/SVneo cells induced upregulation of PIP5K1, leading to PIP2 accumulation and increased trophoblast apoptosis via disruption of the Bcl-2/Bax balance. Silencing of PIP5K1 restored PIP2 homeostasis and attenuated apoptosis. Importantly, these molecular alterations were recapitulated in placental tissues from ICP patients, confirming activation of the PIP5K1-PIP2 axis in vivo. Collectively, our findings identify a spatially resolved PA-PIP5K1-PIP2 lipid signaling cascade that links bile acid-induced metabolic stress to trophoblast apoptosis and placental dysfunction in ICP.

Keywords:  5‐bisphosphate; bile acids; intrahepatic cholestasis of pregnancy; phosphatidylinositol‐4; placental metabolism; trophoblast apoptosis

DOI:  https://doi.org/10.1002/mrd.70105
J Immunol. 2026 Apr 15. pii: vkaf371. [Epub ahead of print]215(4):

CX3CR1 regulates the immune microenvironment in the placenta.

Samuel H Leeds, Nickolas Neokosmidis, David M Haas, Gregory T Knipp, Christoph Konradt.

  The immune environment at the maternal-fetal interface is highly regulated and changes depending on the stage of pregnancy. Any dysregulation or imbalance of the pro- and anti-inflammatory stages can disrupt placental development and can lead to various obstetric disorders, such as miscarriage, preterm birth, and preeclampsia. Several inhibitors interfering with inflammatory pathways have been tested to treat dysregulated inflammation during pregnancy, but they were associated with adverse responses to mother and child. Therefore, understanding factors regulating immune responses at the maternal-fetal interface could lead to the discovery of novel therapeutic targets that prevent detrimental pregnancy outcomes caused by inflammation without risks to mother and child. The fractalkine receptor CX3CR1 is crucially involved in inflammatory processes. Additionally, accumulating evidence has indicated a contribution of CX3CR1 in the pathogenesis of obstetric disorders, including preeclampsia and miscarriage. In this study, we investigated the immune regulatory role of CX3CR1 at the maternal-fetal interface. Our results demonstrate widespread expression of CX3CR1 in placental/decidual immune cells but most prominently on maternal and fetal macrophages and monocytes. Moreover, this study demonstrates a crucial role of CX3CR1 in regulating the immune cell environment and highlights an importance in the formation of maternal sinusoids within the placental labyrinth zone. Combined, our data demonstrate an important immunoregulatory role of CX3CR1 at the maternal-fetal interface. Therefore, the CX3CL1/CX3CR1 axis could be a potential therapeutic target used to prevent detrimental pregnancy outcomes resulting from a dysregulated immune environment.

Keywords:  cytokine receptors; monocytes/macrophages; reproductive immunology; transgenic/knockout mice

DOI:  https://doi.org/10.1093/jimmun/vkaf371
iScience. 2026 May 15. 29(5): 115584

Dissecting placental host-pathogen interactions: Rift Valley fever virus infection in early human trophoblast stem cells.

Yong-Dae Gwon, Sandra Haider, Martin Knöfler, Matthew Bradley, Johan Henriksson, Magnus Evander.

  Rift Valley fever virus (RVFV) is a mosquito-borne Phlebovirus and zoonotic pathogen affecting maternal-fetal health. Vertical transmission is linked to miscarriage and severe fetal outcomes, but mechanisms of placental pathogenesis remain unclear. We used first-trimester human trophoblast stem cells (hTSCs) to model infection at the maternal-fetal interface. Immunofluorescence, qRT-PCR, western blotting, and single-cell transcriptomics showed that hTSCs are highly susceptible to RVFV. Strand-specific viral transcriptomics confirmed the ambisense S segment and revealed preferential transcription of the M and S segments over L. RVFV induced G1 arrest, impairing trophoblast proliferation and differentiation, and drove widespread transcriptional reprogramming, including strong interferon lambda 1 (IFNL1) but modest type I interferon responses, and dysregulation of inflammatory and preeclampsia-associated genes such as RUNX1 and TGFBRAP1. Recombinant IFN-λ pretreatment reduced RVFV protein expression, highlighting hTSCs as a robust model and IFN-λ as a promising antiviral strategy.

Keywords:  pathogenic organism; stem cells research; transcriptomics

DOI:  https://doi.org/10.1016/j.isci.2026.115584
J Physiol. 2026 Apr 19.

Physiological and anatomical determinants of placental drug transfer.

Rohan M Lewis, Anandita Umapathy, Jane K Cleal, Bram G Sengers.

  Understanding how pharmaceuticals cross the placenta is central to balancing effective maternal therapy with fetal safety. Computational and physiologically based pharmacokinetic models are powerful tools for predicting fetal drug exposure, but their accuracy depends on identifying the rate-limiting determinants of placental transfer. These include placental anatomy, the routes available for paracellular diffusion, and the cellular localisation and membrane polarisation of drug transporters. The placenta both limits and mediates fetal exposure: it clears pharmaceuticals from the fetal circulation yet provides the principal route by which drugs reach the fetus. Transfer depends on a drug's physicochemical properties, especially molecular size and lipid solubility, and the presence of specific transport mechanisms. Net fetal exposure reflects the combined effects of diffusion and transporter-mediated fluxes, plasma protein affinity, with a smaller contribution from placental metabolism. At the anatomical level recent advances in our understanding of placental ultrastructure have provided new routes allowing fetal exposure via diffusion. At the molecular level, defining transporter expression and polarisation is challenging and the literature is often inconsistent, reflecting methodological limitations. Single-cell and single-nucleus transcriptomics provide valuable insights into cell-specific gene expression, although not necessarily protein localisation. Spatial mass spectrometry offers complementary information on protein abundance and polarity but remains limited by resolution. Effective models require a strong foundation in physiology and anatomy. A key limitation to modelling placental drug transfer is clearly determining the cellular localisation and membrane polarisation of drug transporters, and addressing this question is key to developing more effective predictive models.

Keywords:  endothelium; placenta; syncytiotrophoblast; transport

DOI:  https://doi.org/10.1113/JP289604
Biochem Biophys Res Commun. 2026 Apr 14. pii: S0006-291X(26)00534-6. [Epub ahead of print]819 153770

Egfl7 regulates embryonic angiogenesis and placental vascular function in mice.

Minjeong Kim, Seunghun Han, Hyeon Ju Park, Jin Soo Lee, Ki-Hoan Nam, Seul Gi Park.

  Epidermal growth factor-like domain 7 (Egfl7) is a secreted protein expressed in endothelial cells and plays an important role in angiogenesis and vascular stabilization. Previous studies have suggested an association between Egfl7 deficiency and vascular abnormalities; however, the specific functional roles of Egfl7 during the early stages of angiogenesis in embryonic development have not been fully elucidated. Therefore, in this study, we systematically investigated the functional role of Egfl7 during embryonic development using an Egfl7 knockout (KO) mouse model. Analysis of the embryonic model revealed that Egfl7 KO embryos exhibited increased partial lethality and growth retardation. These developmental abnormalities were accompanied by a marked reduction in placental vascular formation and decreased expression of the fatty acid transport proteins (Fatp4, Fatp6, and Fabp3), indicating impaired placental nutrient transfer function. Furthermore, reduced expression of Vegfr1 and Vegfr2 in the placenta, together with consistent downregulation of angiogenesis-related genes, was observed, suggesting that Egfl7 regulates multiple stages of angiogenesis, including vascular stabilization, sprouting, and branching. In addition, morphological abnormalities observed in the heart demonstrated that Egfl7 deficiency affects overall cardiovascular development beyond placental vascular defects. Taken together, these findings clearly demonstrate that Egfl7 is an essential regulatory factor for the initiation and maintenance of angiogenesis during physiological embryonic development, and suggest that modulation of Egfl7-mediated pathways may represent a potential therapeutic strategy for diseases associated with abnormal vascular growth.

Keywords:  Angiogenesis; Egfl7; Embryo; Placenta

DOI:  https://doi.org/10.1016/j.bbrc.2026.153770
Placenta. 2026 Mar 03. pii: S0143-4004(26)00073-1. [Epub ahead of print]179 103-112

Placental handling of glucose in the human - beyond the maternal-fetal glucose gradient.

Tore Henriksen, Trond M Michelsen.

  Glucose is the primary energy substrate for the human fetus, essential for brain development and overall growth. Traditionally, fetal glucose supply has been attributed to the maternal-fetal glucose gradient. However, emerging evidence indicates that the placenta plays an active role in regulating glucose availability through its own metabolic processes. This brief review aims to synthesize current knowledge on placental glucose handling in uncomplicated human pregnancies, emphasizing mechanisms beyond passive transfer and quantitative aspects. The placenta exhibits dynamic glucose metabolism, including consumption, storage, and endogenous production. Glycogen pools within placental cells are more likely endogenous sources of glucose than gluconeogenesis. Placental endogenous glucose may represent an auxiliary system that safeguards fetal glucose supply during maternal hypoglycemia and/or increased fetal demand. In vivo studies demonstrate that up to 70% of glucose released to the fetus can originate from placental sources at certain time points. Aerobic glycolysis (with lactate production) is a prominent feature of placental metabolism, with substantial lactate export to the maternal circulation. This energy loss is partly compensated for by uptake of maternal ketone bodies and acetate, highlighting the placenta's flexibility in substrate utilization. These adaptations underscore the placenta's dual role: maintaining its own structural and functional integrity while ensuring fetal oxygen and energy needs. Understanding these mechanisms is critical for defining the partition of energy between the placenta and fetus and its implications for fetal growth, particularly under conditions of maternal nutrient restriction. Insights into placental glucose metabolism may inform strategies for understanding and managing growth deviations and guide development of artificial placental systems.

Keywords:  Aerobic glycolysis; Fetal energy supply; Gluconeogenesis; Glycogen storage; Ketone utilization; Lactate; Maternal–fetal glucose gradient; Placental glucose metabolism

DOI:  https://doi.org/10.1016/j.placenta.2026.03.002
Reprod Toxicol. 2026 Apr 17. pii: S0890-6238(26)00093-6. [Epub ahead of print]143 109250

Lipoic acid attenuated hypoxia-induced disruption of mitochondrial respiration in an in vitro human trophoblast model.

Jaeha Hwang, Wonhyoung Park, Gwonhwa Song, Whasun Lim, Sunwoo Park.

  Preeclampsia is a pregnancy-specific hypertensive disorder characterized by abnormal placentation, trophoblast dysfunction, and systemic endothelial injury. Mitochondrial dysfunction and impaired energy metabolism have been implicated in its pathogenesis. This in vitro study investigated the effects of a CoCl2-induced hypoxia-mimetic condition on trophoblast mitochondria and evaluated whether lipoic acid (LA) could mitigate the associated impairment. In HTR-8/SVneo cells, CoCl₂ significantly reduced cell viability and the expression of oxidative phosphorylation (OXPHOS)-related genes. In addition, it impaired mitochondrial respiration by suppressing the oxygen consumption rate. LA markedly restored the reduced expression of OXPHOS-associated genes and modestly improved cell viability, and attenuated mitochondrial membrane potential disruption under the 100 μM CoCl₂ conditions. LA also showed partial recovery of trophoblast migration and TIE2 expression under CoCl₂-induced stress. These findings indicate that LA may partially attenuate CoCl₂-induced mitochondrial and functional impairment in trophoblasts in vitro. Further studies are needed to clarify the underlying mechanisms and the relevance of these findings to preeclampsia.

Keywords:  Chemical hypoxia; HTR-8/SVneo trophoblasts; Lipoic acid; Oxidative phosphorylation; Preeclampsia

DOI:  https://doi.org/10.1016/j.reprotox.2026.109250
J Nutr Biochem. 2026 Apr 22. pii: S0955-2863(26)00130-0. [Epub ahead of print] 110388

High-Fat Diet Induces Preeclampsia-Like Phenotypes Associated with Impaired Decidualization and NF-κB Activation.

Miaomiao Zhao, Yanxin Xu, Xingyu Yan, Cong Zhang.

  Preeclampsia (PE), a life-threatening hypertensive disorder of pregnancy, remains a leading cause of maternal-fetal morbidity with unclear pathogenesis. While traditional studies focus on placental dysfunction, the critical role of decidualization-a prerequisite for placental implantation-has been underemphasized. Here, we demonstrate that a high-fat diet (HFD) predisposes mice to PE-like phenotypes, including hypertension, proteinuria, glomerular injury, and placental-fetal growth restriction, which are accompanied by impaired decidualization. HFD triggers robust inflammatory responses in decidual tissue, evidenced by upregulated IL-1β/IL-6/TNF-α and hyperactivated NF-κB signaling, which correlate with reduced expression of decidualization regulators (Bmp2, Wnt4) and marker genes (Dtprp, Prl8a2). These changes lead to compromised decidual vascularization, reduced polyploid cell differentiation, and impaired placental morphogenesis. Our findings reveal a novel association whereby HFD-induced inflammation is linked to disrupted decidual-placental crosstalk via NF-κB activation, providing mechanistic insights into PE pathogenesis and highlighting decidualization as a potential therapeutic target.

Keywords:  Decidualization; High-fat diet; Inflammation; NF-κB; Preeclampsia

DOI:  https://doi.org/10.1016/j.jnutbio.2026.110388