bims-placeb Biomed News
on Placental cell biology
Issue of 2026–10–11
thirteen papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences
  1. Spatio-temporal expression of E-cadherin mediates trophoblast lineage transitions during human placentation.
  2. Late-onset preeclampsia is characterized by accelerated placental aging.
  3. Early Peri-conceptional Alcohol Exposure before Implantation Disrupts Placental Development across Gestation.
  4. A perfusable first-generation endometrial microvascular model to study human spiral artery remodeling in pregnancy.
  5. Sex-linked placental DNA methylation associated with early-onset preeclampsia.
  6. Multi-omic profiling defines subtype-specific extracellular vesicle signatures in early human pregnancy.
  7. A bioengineered model of human placental exposure to environmental metals during pregnancy.
  8. Influenza A virus infection induces immune dysregulation in the placenta and fetus without vertical transmission in nonhuman primates.
  9. Spondweni virus infection in pregnant rhesus macaques causes placental pathology without apparent fetal harm.
  10. A Continuous In Vitro Culture Protocol for Mouse Embryos From the Zygote to the Egg Cylinder Stage.
  11. PPAR-γ alleviates preeclampsia-associated placental oxidative stress with involvement of the PI3K/Akt signaling pathway.
  12. Maternal PM2.5 exposure induces preeclampsia-like phenotypes in mice through placental angiogenic dysfunction and lncRNA-RUNX1 dysregulation.
  13. Temporal transcriptomics identifies transregulation by multiple lncRNAs in human iPSCs.
  1. Mol Biol Rep. 2026 Oct 08. pii: 1678. [Epub ahead of print]53(1):
    Spatio-temporal expression of E-cadherin mediates trophoblast lineage transitions during human placentation.
    Enoch Appiah Adu-Gyamfi, Ethan Backes.
      Human placentation relies on the precise differentiation of embryo-derived trophoblasts into specialized lineages, a process strictly regulated by the spatio-temporal expression of key genes. Herein, we report that the expression of the transmembrane glycoprotein, known as E-cadherin, fluctuates dynamically across distinct trophoblast subpopulations rather than acting as a static structural tether. Along the villous pathway, E-cadherin expression initially increases to facilitate the aggregation of cytotrophoblast cells (CTs) and is subsequently downregulated via transcriptional repression, enzymatic cleavage and physical compressive forces for the CTs to fuse into the syncytiotrophoblast lineage. Conversely, along the extravillous pathway, its transient downregulation characterizes an epithelial-to-mesenchymal transition that permits trophoblast invasion into the decidua, followed by its upregulation in the endovascular trophoblasts to potentially facilitate vascular adhesion and spiral artery remodeling. Dysregulation of this expression pattern of E-cadherin is evident in the placenta of pregnancies complicated by preeclampsia or fetal growth restriction. To advance the field, future research must transition from descriptive profiling to functional mechanisms by defining the precise intracellular degradation pathways of E-cadherin in trophoblast lineages and then clarify whether the upstream regulators operate in linear or parallel networks. Utilizing advanced biophysical tools and spatial transcriptomics will help clarify how tissue stiffness, fluid shear stress, and local immune cells mechanically and immunologically trigger this E-cadherin switch via mechanosensitive channels. Translational studies should explore the feasibility of using circulating soluble E-cadherin fragments in maternal blood as an early biomarker of defective placentation.
    Keywords:  E-cadherin; Placenta; Preeclampsia; Pregnancy; Trophoblast
    DOI:  https://doi.org/10.1007/s11033-026-12837-0
  2. Proc Natl Acad Sci U S A. 2026 Oct 13. 123(41): e2614827123
    Late-onset preeclampsia is characterized by accelerated placental aging.
    Anya L Arthurs, Rudrarup Bhattacharjee, Melanie D Smith, Dulce L Medina Garcia, Ellen Menkhorst, German Mora, Jessica M Williamson, Lynda K Harris, Jose M Polo, David A MacIntyre, Claire T Roberts.
      Late-onset preeclampsia (LOPE) is a major pregnancy complication characterized by hypertension and placental dysfunction, resolving only upon delivery. Here, we show that LOPE placentae undergo accelerated molecular aging, marked by telomere attrition, DNA damage, and trophoblast senescence. Using primary placental tissue and trophoblast organoids, we demonstrate oxidative stress as a driver of telomere shortening and angiogenic imbalance. Inflammation did not alter placental aging trajectories. Antioxidant treatment (superoxide dismutase) preserved telomere length, reduced DNA damage, and restored angiogenic balance, highlighting oxidative stress as a modifiable determinant of placental aging. We identify reduced expression of telomeric repeat-containing RNAs (TERRAs) as a molecular hallmark of LOPE, and show that antisense oligonucleotide-mediated TERRA depletion exacerbates telomere erosion and senescence. Together, these findings delineate oxidative stress and TERRA loss as mechanisms driving placental decline, establish trophoblast organoids as a tractable model of placental aging, and reveal potential therapeutic avenues for mitigating preeclampsia-associated placental dysfunction.
    Keywords:  aging; inflammation; oxidative stress; placenta; preeclampsia
    DOI:  https://doi.org/10.1073/pnas.2614827123
  3. Res Sq. 2026 Aug 14. pii: rs.3.rs-10319561. [Epub ahead of print]
    Early Peri-conceptional Alcohol Exposure before Implantation Disrupts Placental Development across Gestation.
    Yijen Wu, Devin Raine Cortes, Dalton West, Noah William, Sean Hartwick, Thomas Becker-Szurszewski, Margaret Stapleton, Gabriella Saladino, Joseph Simmons Iii, Amanda N Sferruzzi-Perri, Gary Kohanbash, Chaim Sneiderman, Uma R Chandran, Jiefei Wang, Ana Cristancho, Chris McKennan, Debora Cerqueira, Jacqueline Ho, Sivakama Bharathi, Eric Goetzman, John Chaillet, Anthony Christodoulou.
      Fetal Alcohol Spectrum Disorder, caused by prenatal alcohol exposure, remains a major public health concern, affecting up to 1 in 20 U.S. schoolchildren. Pregnancy is typically not recognized until six weeks of gestation, alcohol exposure often occurs unknowingly during the peri-conceptional period, a highly vulnerable developmental window of oocyte maturation. The placenta is increasingly recognized as a mediator of alcohol-induced neurodevelopmental risk through the placenta-brain axis. We characterize peri-conceptional alcohol exposure on placental development in a mouse PCA model mimicking human drinking patterns. Single-cell transcriptomic analyses on late gestation placentas revealed disruption of extracellular matrix and collagen-remodeling pathways within the labyrinth; processes essential for placental vascular development. Mitochondria isolated from E17.5 placentas showed compromised respiration. We assess placental vascular functions with non-invasive dynamic contrast-enhanced MRI, enabling analysis across placental compartments for longitudinal evaluation of perfusion, substrate delivery, and contractile function. We demonstrate that PCA exposure arrests placental vascularization, perfusion, and morphological maturation. PCA exposure before implantation altered long-term placental programming, resulting in impaired placental perfusion and mitochondrial functions across gestation. These findings implicate placental dysfunction as a critical mechanism in Fetal Alcohol Spectrum Disorder pathogenesis and identify extracellular matrix remodeling and mitochondria as potential therapeutic targets following PCA exposure.
    DOI:  https://doi.org/10.21203/rs.3.rs-10319561/v1
  4. Lab Chip. 2026 Oct 09.
    A perfusable first-generation endometrial microvascular model to study human spiral artery remodeling in pregnancy.
    Sebastian Naranjo, Madison E Fletcher, Noo Li Jeon, Joyce Y Wong, Catherine Klapperich.
      Invasive placental cells, extravillous trophoblasts (EVT), remodel maternal vasculature to meet metabolic needs of the growing fetus. Dysregulation of spiral artery remodeling (SAR) is a characteristic of preeclampsia (PE), a severe pregnancy-related condition. We developed a modular new approach methodology (NAM) of human endometrial-specific vascular networks in a polystyrene (PS) microfluidic chip to recapitulate the intricate endometrial vascular microenvironment to investigate SAR. We leveraged the self-assembly of human endometrial microvascular endothelial cells (HEMEC) and normal human lung fibroblasts (NHLF) to successfully develop patent endometrial vascular networks after 3 days of culture. Exogenous proangiogenic factors significantly improved vascular density while maintaining intrinsic endometrial vascular properties. Treatments of menstrual cycle phase-specific hormones differentially affected endometrial vascular density, diameter, permeability, and endogenous secretions of proangiogenic proteins. We evaluated integration potential of EVT cell lines HTR8/SVneo and JEG-3. We measured decreased barrier function and observed increased presence of apoptotic HEMECs after 3 days of tri-culture with JEG-3 cells, whereas HTR8/SVneo-induced apoptosis remained statistically unchanged across days 1 and 3 of integration. Moreover, we confirm HTR8/SVneo and JEG-3 cells differentially interact with HEMEC vasculature and the surrounding perivascular niche. These studies demonstrate the utility of our model to study endometrial vascularization and EVT remodeling.
    DOI:  https://doi.org/10.1039/d6lc00513f
  5. Res Sq. 2026 Aug 13. pii: rs.3.rs-10541872. [Epub ahead of print]
    Sex-linked placental DNA methylation associated with early-onset preeclampsia.
    Hannah J Illing, Icíar Fernández-Boyano, Amy M Inkster, Linda M Ernst, Gregory E Miller, Ann E Borders, Wendy P Robinson.
      Impaired placental development and function is a necessary feature of early-onset preeclampsia (EOPE), a severe pregnancy complication. We do not fully understand the molecular changes underlying EOPE; however, we know that DNA methylation, a chemical mark on DNA, can be measured to identify changes associated with EOPE. Typically, human cells have 22 pairs of autosomal chromosomes and one pair of sex chromosomes; females have two X chromosomes (XX) and males one X and one Y chromosome (XY). This is the first study to investigate and identify an association between EOPE and X and Y chromosome DNA methylation in the placenta. We used DNA methylation data from 843 placentas (XX = 386, XY = 457). We identified differences in X and Y chromosome DNA methylation associated with EOPE-pathology. Most differences in DNA methylation were observed in both males and females. Some of the associations were in genes which may have relevance to the pathophysiology of EOPE in the placenta. Our study highlights that there are important findings on the X and Y chromosomes that have been missed by their routine exclusion in previous studies.
    DOI:  https://doi.org/10.21203/rs.3.rs-10541872/v1
  6. Biol Reprod. 2026 Oct 05. pii: ioag220. [Epub ahead of print]
    Multi-omic profiling defines subtype-specific extracellular vesicle signatures in early human pregnancy.
    Kobe A Abney, Taylor Hollingsworth, Alexandra Schneider, Elizabeth M Brown, Hossein Fazelinia, Lynn A Spruce, Rita Leite, Samuel Parry, Nadav Schwartz, Colin C Conine, Rebecca A Simmons.
      Early human pregnancy (11-15 weeks) is a critical period when placental dysfunction begins but remains clinically undetectable, preventing early intervention for pregnancy complications. This highlights a pressing need for circulating biomarkers that can signal the onset of a complication. Circulating extracellular vesicles (EVs) carry bioactive cargo that reflect originating cell activity in real-time, positioning them as early biomarkers of pregnancy complications. While pregnancy studies have identified plasma EV cargo alterations across complications, studying small EVs alone-the field standard-or bulk EVs together obscures pathological changes that may manifest preferentially in one population. To address this, we performed the first multi-omic comparison of small and large plasma EVs from healthy pregnancies at 11-13 weeks (n=10) to establish subtype-specific cargo differences and provide a reference for normal pregnancy EV biology. We quantified mitochondrial DNA (mtDNA), performed transcriptomics (mRNAs, miRNAs) and proteomics to define small and large EV signatures. Large EVs were preferentially enriched for mitochondrial cargo including DNA, transcripts, and proteins as well as hypoxia response, endocrine signaling, and VEGF signaling related transcripts and proteins. In contrast, small EVs were enriched for canonical EV markers and basement membrane proteins. Additionally, we found that EV miRNA composition was similar across EV subtypes with only 7 miRNAs differentially abundant between small and large EVs. These distinct small and large EV cargo signatures underscore the importance of profiling both populations for liquid biopsy potential. Together these data provide a baseline for future studies linking EV signature alterations to placental dysfunction and adverse pregnancy outcomes.
    Keywords:  Pregnancy; extracellular vesicles; maternal-fetal communication; mitochondria; placenta; proteomics; transcriptomics
    DOI:  https://doi.org/10.1093/biolre/ioag220
  7. Nat Biomed Eng. 2026 Oct 09.
    A bioengineered model of human placental exposure to environmental metals during pregnancy.
    Pouria Fattahi, Mousa Younesi, Won Dong Lee, Keumrai Whang, Se-Jeong Kim, Taewook Kang, Lauren M Aleksunes, Dan Dongeun Huh.
      Exposure of pregnant women to toxic metals is an environmental health issue associated with pregnancy complications. Advancing our biological understanding of this problem and mitigating its adverse effects have been challenged by the ethical constraints of human participant research during pregnancy. Here we present a microphysiological system to experimentally simulate and investigate human placental exposure to environmental metals in maternal circulation. An in vitro analogue of the maternal-fetal interface and its dynamic tissue-specific environment are constructed using primary human placental cells grown in a microfluidic device. Using cadmium as a representative toxicant, we show how this system can be used to model the human placental barrier subjected to the flow of cadmium-containing maternal blood and its adverse biological responses and impaired tissue function. Through mechanistic investigation of maternal-to-fetal cadmium transport in this model, we reveal that efflux membrane transporters expressed by trophoblasts may play a protective role against cadmium-induced toxicity. Finally, we demonstrate the potential use of the microphysiological system for discovering metabolic biomarkers for detection and monitoring of cadmium-induced placental dysfunction.
    DOI:  https://doi.org/10.1038/s41551-026-01801-9
  8. Sci Adv. 2026 Oct 09. 12(41): eaee9861
    Influenza A virus infection induces immune dysregulation in the placenta and fetus without vertical transmission in nonhuman primates.
    Orlando Cervantes, Sidney Sun, Hazel Huang, Briana Del Rosario, Hong Zhao, Amanda Li, Andrew Vo, Gygeria Manuel, Roslyn Van Abel, Jeff Munson, John Cornelius, Raj P Kapur, Miranda Li, Edmunda Li, Hanning Li, Alexandra Christodoulou, Melissa Berg, Britni Curtis, Elizabeth Miller, Shannon Ruff, Brenna Menz, Solomon Wangari, Audrey Germond, Audrey Baldessari, Chris English, W McIntyre Durning, Thomas B Lewis, Megan N Fredericks, Mara Maughan, Austyn Orvis, Michelle Coleman, Lakshmi Rajagopal, Deborah H Fuller, Kristina M Adams Waldorf.
      Influenza A virus (IAV) infection during pregnancy is associated with stillbirth and preterm birth. We hypothesized that maternal IAV infection disrupts placental and fetal immune networks in ways that correlate with disease severity. Pregnant pigtail macaques were inoculated with IAV [A/California/07/2009 (H1N1)] and underwent delivery and fetal necropsy 5 days postinfection (N = 11), with comparison to uninfected controls (N = 16). Stillbirth occurred in 18% of infected pregnancies and in no controls. Although vertical transmission was not observed, low levels of viral RNA were detected in two placentas. Maternal infection was associated with induction of a type I interferon response in the placenta and altered innate and adaptive immune cell populations in the fetus. Maternal disease metrics (e.g., lung viral load and interferon-α) were rarely associated with placental immune perturbations but frequently linked to fetal immune cell populations (CD4+ and CD8+ T cells and monocyte subsets). Collectively, these data indicate that maternal IAV disease severity is associated with dysregulated fetal immunity.
    DOI:  https://doi.org/10.1126/sciadv.aee9861
  9. bioRxiv. 2026 Aug 10. pii: 2026.08.10.743875. [Epub ahead of print]
    Spondweni virus infection in pregnant rhesus macaques causes placental pathology without apparent fetal harm.
    Hunter J Ries, Livia Romanov, Maria C Charles, Chelsea M Crooks, Carson DePagter, Alex Richardson, Grace A VanSleet, Andrea M Weiler, Jens C Eickhoff, Katharina S Stewart, Leandro B C Teixeira, Eric Peterson, Michele Schotzko, Heather A Simmons, Jenna R Rosinski, Lauren E Raasch, Anna S Jaeger, Elaina R Razo, Emma L Mohr, David H O'Connor, Christina M Newman, Matthew T Aliota, Thomas C Friedrich.
      The 2015-2016 Zika virus (ZIKV) epidemic revealed the potential of flaviviruses to emerge rapidly, cause severe disease, and affect pregnancy outcomes. In 2016, Spondweni virus (SPOV), the closest known relative of ZIKV, was detected in mosquitoes in Haiti, suggesting it may also have the potential to emerge in the Western Hemisphere. The risks that close relatives of ZIKV pose to pregnant individuals are not well understood. Previously, we showed that SPOV can cause fetal demise, placental pathology, and vertical transmission in a mouse model. Here we report SPOV's pathogenic potential in pregnant rhesus macaques. We inoculated four macaques with SPOV at gestational day 30 (early first trimester) and compared their viral loads and fetal outcomes with those of macaques infected in the first trimester with either African-lineage ZIKV (ZIKV-DAK) or an Asian-lineage ZIKV isolate from Puerto Rico (ZIKV-PR) in previous studies. Plasma viremia persisted 10-31 days in SPOV-inoculated dams, whereas viremia resolved within 10-17 days for ZIKV-DAK and 5-52 days for ZIKV-PR. Cesarean deliveries near term (gestational day 152-157) revealed no demise, premature birth, or gross abnormalities in fetuses of dams inoculated with SPOV or ZIKV-PR. In contrast, under near-identical conditions, all ZIKV-DAK-inoculated dams experienced fetal demise between 12 and 20 days post-inoculation. At cesarean section, we did not detect SPOV RNA above the limit of detection in maternal (e.g., spleen, liver), placental, or fetal tissues, in contrast to previous findings with ZIKV-PR. Histological analysis revealed mononuclear/lymphohistiocytic villitis in all placentas of SPOV-exposed macaques, along with other pathological changes in individual placentas. Our findings suggest that SPOV infection of macaques in early pregnancy may result in placental pathology without overt fetal harm. Our results suggest that flaviviruses in the Spondweni serocomplex, which includes ZIKV and SPOV, may vary in their pathogenic potential during pregnancy.
    Author Summary: Zika virus (ZIKV) can cause fetal harm. Does this risk extend to its closest known relative, Spondweni virus (SPOV)? Should SPOV circulate in humans, what risks would it pose in pregnancy? SPOV can injure fetuses in immunocompromised mice, but the physiology of pregnancy in mice differs greatly from that of humans. We therefore infected pregnant rhesus macaques with SPOV during early gestation and compared maternal viremia, placental pathology, and fetal outcomes with macaques infected with African- or Asian-lineage ZIKVs at the same gestational age. All fetuses survived to near-term pregnancy, fetal tissues were negative for SPOV RNA, and fetal growth tracked within expected ranges. Nonetheless, all SPOV-exposed pregnancies showed placental injury, including mononuclear/lymphohistiocytic villitis and maternal vascular malperfusion. Despite the absence of detectable SPOV RNA in fetal tissues, SPOV RNA persisted at term in maternal-fetal interface tissues in two of four animals. These data indicate placental injury without detectable vertical transmission in this translational model. Our results suggest that SPOV and ZIKV display a wide range of risks to the developing fetus. Identifying viral and host factors that increase the potential for fetal harm will be important for assessing risks posed by emerging viruses in this family.
    DOI:  https://doi.org/10.64898/2026.08.10.743875
  10. Dev Growth Differ. 2026 Oct;68(8): e70070
    A Continuous In Vitro Culture Protocol for Mouse Embryos From the Zygote to the Egg Cylinder Stage.
    Rui Shibata, Hiromi Shimojo, Hiroshi Sasaki.
      Mouse embryos undergo drastic morphological changes during implantation, but analysis of this process has been challenging because it occurs within the uterus. Various in vitro culture systems supporting development beyond implantation have been established since the 1970s. More recently, 3D-geec, which supports embryos from the peri-implantation to egg cylinder stages while preserving their three-dimensional organization, was developed as a useful platform for studying this critical period. Combining 3D-geec with genome editing in zygotes or experimental manipulation of embryos should further facilitate mechanistic studies of these stages. In this study, to enable such approaches, we established an in vitro culture protocol that supports continuous development of mouse embryos from the zygote to the egg cylinder stage. Embryos cultured from the zygote to the late blastocyst stage in KSOMAA medium were not compatible with 3D-geec. These embryos exhibited reduced cell numbers, delayed development, and reduced mTORC1 activity, which regulates cell growth and proliferation. The use of Advanced IVC medium supplemented with 10% fetal bovine serum (FBS) during the blastocyst stage substantially rescued these defects, and the resulting late blastocysts underwent further development into egg cylinders in 3D-geec. Furthermore, genome-edited embryos generated from zygotes developed into egg cylinders using this protocol and were successfully subjected to time-lapse imaging during 3D-geec. Thus, this culture protocol enables continuous in vitro development from the zygote to the egg cylinder stage and provides a platform for studying gene function and cellular dynamics during peri-implantation and early postimplantation development.
    Keywords:  embryo; in vitro technology; mouse; peri‐implantation stage; zygote
    DOI:  https://doi.org/10.1111/dgd.70070
  11. J Steroid Biochem Mol Biol. 2026 Oct 03. pii: S0960-0760(26)00190-1. [Epub ahead of print]266 107124
    PPAR-γ alleviates preeclampsia-associated placental oxidative stress with involvement of the PI3K/Akt signaling pathway.
    Jiangying Liu, Yiting Hong, Shengjun You, Zhenzhu Dong, Jingliang Sun, Zhangshan Xu.
       BACKGROUND: Preeclampsia (PE) is characterized by placental dysfunction and oxidative stress. This study investigated whether peroxisome proliferator-activated receptor-γ (PPAR-γ) protects against PE through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway.
    METHODS: GSE10588 was analyzed using differential expression, single-sample gene set enrichment analysis, CIBERSORT, and weighted gene co-expression network analysis. PPAR-γ expression was examined in placentas from six patients with PE and six healthy pregnant women. Lipopolysaccharide-treated HTR-8/SVneo cells and N-nitro-L-arginine methyl ester-induced PE rats were used as experimental models. PPAR-γ was modulated by overexpression or rosiglitazone, while PI3K was inhibited with LY294002. Trophoblast function, oxidative stress, maternal blood pressure, proteinuria, placental injury, and PI3K/Akt signaling were evaluated.
    RESULTS: PPAR-γ expression correlated positively with oxidative phosphorylation and PI3K/Akt pathway activity and was associated with altered placental immune-cell profiles. PPAR-γ expression was reduced in PE placentas. PPAR-γ overexpression increased trophoblast viability and invasion, reduced apoptosis, and restored antioxidant enzyme activities after lipopolysaccharide exposure. These effects were accompanied by increased PI3K and Akt phosphorylation and were attenuated by LY294002. In L-NAME-treated rats, rosiglitazone improved hypertension, proteinuria, placental injury, and antioxidant enzyme activities, accompanied by increased PI3K and Akt phosphorylation.
    CONCLUSION: PPAR-γ activation alleviates trophoblast dysfunction and placental oxidative injury in PE, at least partly through PI3K/Akt signaling, and may represent a potential therapeutic target.
    Keywords:  PI3K/Akt signaling pathway; PPAR-γ; bioinformatics analysis; oxidative stress; preeclampsia
    DOI:  https://doi.org/10.1016/j.jsbmb.2026.107124
  12. J Environ Manage. 2026 Oct 03. pii: S0301-4797(26)02526-0. [Epub ahead of print]418 131066
    Maternal PM2.5 exposure induces preeclampsia-like phenotypes in mice through placental angiogenic dysfunction and lncRNA-RUNX1 dysregulation.
    Li Ma, Zhihua Gong, Guangke Li, Nan Sang.
      Preeclampsia (PE) is an idiopathic gestational disorder defined by placental structural abnormalities, systemic inflammatory activation, angiogenic factor imbalance, and endothelial dysfunction. While existing epidemiological studies have established a correlational association between maternal fine particulate matter (PM2.5) exposure and elevated PE risk, the specific underlying molecular mechanisms driving this association have not been fully elucidated. Using a C57BL/6J mouse model of maternal PM2.5 exposure via intranasal instillation (3 mg/kg body weight, every other days from gestational day 0.5 to 17.5), we investigated the mechanisms underlying PE-like phenotypes induced by heating-season PM2.5 from northern China. Exposed pregnant mice exhibited significantly elevated blood pressure at E13.5 and E17.5, accompanied by reduced vascular endothelial growth factor (VEGF) and placental growth factor (PLGF) levels, increased urinary protein, and elevated serum levels of the tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and soluble fms-like tyrosine kinase-1 (sFLT-1). Conversely, the endothelial markers endothelin 1 (ET-1) and nitric oxide (NO) remained unchanged. Placentas from PM2.5-exposed mice exhibited abnormal architecture and impaired angiogenesis in the labyrinth region. These phenotypes were consistent with key features of PE. Through transcriptomic profiling, bioinformatics analyses, immunofluorescence, quantitative reverse transcription PCR (RT-qPCR), and chromatin/RNA immunoprecipitation assays, we identified the long noncoding RNAs (lncRNAs) NONMMUT087808.1 and NONMMUT044449.2 as potential regulators of placental development and function that are associated with runt-related transcription factor 1 (RUNX1) dysregulation, suggesting a possible contribution to PE-like phenotypes. Taken together, our findings provide experimental evidence linking exposure to heating-season PM2.5 from northern China with adverse gestational outcomes and highlight the critical need for targeted air pollution mitigation strategies and population-specific health interventions for vulnerable subgroups, including pregnant women.
    Keywords:  Maternal PM(2.5) exposure; Placental angiogenic dysfunction; Preeclampsia; lncRNA–RUNX1 dysregulation
    DOI:  https://doi.org/10.1016/j.jenvman.2026.131066
  13. Genome Res. 2026 Oct 09. pii: gr.282389.126. [Epub ahead of print]
    Temporal transcriptomics identifies transregulation by multiple lncRNAs in human iPSCs.
    Mingfeng Liu, Izabela Mamede, Sajad Sofi, Isabela Pereira, Vishantie Dostal, Alison R S Pashos, Conor McMahon, Aneesh Waikar, George Stephenson, Thomas R Cech, John L Rinn.
      Some long noncoding RNAs (lncRNAs) are known to regulate gene expression. However, the underlying temporal dynamics of lncRNAs influencing gene and epigenetic regulation, and mechanisms of lncRNA regulation in trans, are less understood. To investigate this, we genetically engineer 17 doxycycline-inducible lncRNA transgenes for ectopic expression at the H11 safe harbor locus in human pluripotent stem cells (hiPSCs), and we generate high-density temporal RNA-seq and ATAC-seq profiles. Most lncRNA transgenes are induced at 2 hours and maintain expression through the 96-hour time course. Surprisingly, when we seek to identify gene expression changes due to the lncRNAs, we find that the global transcriptional landscape is dominated by a strong systemic response triggered by doxycycline exposure. We rigorously define this cohort of genes as a Doxycycline-Responsive Gene Signature (DRGS). The DRGS is also present in at least 28 public datasets from dox-inducible transgene studies involving diverse cell types. Next, we determine which lncRNAs exhibit trans-regulatory events. We identify DANCR, FENDRR, LINC00667, LINC00847, LNCPRESS1, and LNCPNKY as lncRNAs that regulate specific transcript expression in trans The downstream target genes encode 53 mRNAs and 10 lncRNAs. None of the target lncRNAs alter gene expression proximal to their own loci (i.e., triggering secondary cis effects). Surprisingly, the target genes of LINC00847 (transcribed from Chromosome 22) are substantially enriched on Chromosome 19, with a preponderance of target genes encoding RNA metabolism and RNA splicing factors. Collectively, our study provides a resource to discern artifacts in the doxycycline-inducible system and identifies temporally regulated targets of 6 lncRNAs for future mechanistic studies.
    DOI:  https://doi.org/10.1101/gr.282389.126
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