bims-placeb 2026-08-16 papers

bims-placeb

Biomed News

on Placental cell biology

Issue of 2026–08–16
fifteen papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences

Diminished Maternal Tryptophan Leads to Sexually Dimorphic Differences in the Placenta-Brain Axis.
Polystyrene microplastics impair trophoblast invasion in vitro and alter microRNA expression targeting the angiogenesis pathway.
Physiological Adaptations of Pregnancy to the Chronic Hypoxia of High Altitude.
Impairment of placental function and maternal-fetal immunity cross-talk by per- and polyfluoroalkyl substances during early pregnancy.
Rift Valley fever virus infects trophoblast cell lines in an LRP1-dependent manner.
Uteroplacental Responses to Physiological Challenges Throughout Pregnancy Using MRI.
PSG2 Impairs Human Trophoblast Function in Preeclampsia by Activating TGF-β/Smad3 to Suppress EMT and MMP2/9 Expression.
Leptin-cholesterol crosstalk in pregnancy: Mechanistic implications for placental function and cardiometabolic programming.
Gestational inhalation of nanoparticles alters placental glucose transporter expression and increases glucose flux in rats.
Trophoblast Retrieval from the Cervix (TRIC) Across Early Gestation: A Multi-Method Assessment of Extravillous Trophoblast Recovery.
Polystyrene nanoplastics induce fetal growth restriction via a novel NMNAT3 depletion cascade disrupting placental mitochondrial energetics and activating ferritinophagic ferroptosis.
Glucocorticoids and placental 11βHSD2 - A systematic review of human studies and animal models.
Temporal reorganization of maternal care during early life stress in mice.
In-situ cryo-ET of mouse embryos reveals cytoplasmic lattices contain ubiquitin-charged E2-E3 ligase assemblies.
Systematic differences in protein stability underlie species-specific developmental tempo.

Nutrients. 2026 Aug 06. pii: 2575. [Epub ahead of print]18(15):

Diminished Maternal Tryptophan Leads to Sexually Dimorphic Differences in the Placenta-Brain Axis.

Rosalind T B Herrington, Zhen Lyu, Sarah E Seda, Emmett E Boling, Andrea K Goldstein, Nathan J Bivens, Zhentian Lei, Tanhaul Islam, Lloyd W Sumner, Trupti Joshi, Cheryl S Rosenfeld.

  Background: Tryptophan (Trp) is critical to mothers and their conceptuses, and this amino acid is the precursor to serotonin (5-HT). 5-HT modulates placenta function and fetal neurodevelopment. It is not clear if the placenta directly synthesizes 5-HT or uses the serotonin transporter (SERT/Slc6a4) to accrue 5-HT from the dam. The hypothesis tested herein is that reduction in maternal Trp leads to reductions in maternal Trp, 5-HT, and 5-hydroxy-3-indoleacetic acid (5-HIAA, metabolite of serotonin) and reductions in these metabolites within the placenta and fetal brain of female and male conceptuses. Methods: Female mice were placed on a reduced tryptophan (Trp) diet (0.1%) or control diet (0.2%). Diets were provided for two weeks prior to breeding (periconception period) until conceptuses were collected at approximately 12.5 days post-coitus (dpc). Results: While no reductions in maternal Trp and 5-HT were observed, both metabolites were significantly reduced in the placenta and fetal brain of male and female conceptuses (p < 0.05). Female conceptuses were susceptible to reductions in maternal Trp with 549 and 29 transcripts altered in the female placenta and fetal brain, respectively, of reduced Trp dams compared to control dams. Transcriptomic changes, such as reduced expression in Slc6a4 and Slc6a19 (transporter for Trp), in placenta of female conceptuses correlated with reductions in Trp and 5-HT amounts. Conclusions: Findings might have clinical importance to pregnant women as they reveal even subtle reductions in one amino acid profoundly influence conceptus development and might lead to sexual disparity in risk for later diseases, including neurobehavioral disorders.

Keywords:  maternal diet; metabolomics; nutrition; pregnancy; serotonin; transcriptomics; trophoblast

DOI:  https://doi.org/10.3390/nu18152575
Environ Toxicol Pharmacol. 2026 Aug 12. pii: S1382-6689(26)00209-7. [Epub ahead of print] 105131

Polystyrene microplastics impair trophoblast invasion in vitro and alter microRNA expression targeting the angiogenesis pathway.

Saikanth Varma, Asim K Duttaroy, Sanjay Basak.

  The presence of microplastics (MPs) in human blood and placenta provides evidence of human exposure to MPs and their accumulation in biological tissues. Adequate trophoblast invasion is essential for normal placentation. However, the effects of MPs exposure on microRNA (miRNA) expression regulating angiogenesis during early placental development on trophoblast function remain poorly understood. In this study, the interaction of polystyrene microplastics (PS-MPs) with the HTR8/SVneo trophoblast cell line was investigated, with a particular focus on miRNA, gene, and protein expression associated with angiogenic and hypoxia-related pathways. Scanning electron microscopy (SEM) revealed PS-MPs adherence and accumulation on the cell membrane. PS-MPs significantly impaired trophoblast invasion and altered the expression of vascular endothelial growth factor (VEGF) and its receptors. Increased miRNA expression, known to regulate angiogenesis, suggests alterations in the transcriptome underlying the observed reduction in invasion. MiRNAs dysregulated in inadequate trophoblast invasion were significantly altered. Overall, PS-MP exposure impairs trophoblast invasion and altering trophoblast miRNA expression targeting VEGF, activating hypoxia mediators, thereby affecting early placental functions.

Keywords:  Invasion; MicroRNAs; Microplastics; Migration; Placenta; Trophoblast

DOI:  https://doi.org/10.1016/j.etap.2026.105131
Physiol Rev. 2026 Aug 14.

Physiological Adaptations of Pregnancy to the Chronic Hypoxia of High Altitude.

Germán A Arenas, Emilio A Herrera, Bernardo J Krause, Dino A Giussani, Colleen G Julian, Lorna G Moore, Ramón A Lorca.

  The chronic hypoxia experienced by high-altitude residents profoundly impacts pregnancy, influencing maternal health, placental function, and the growth and development of the fetus. Exposure to chronic hypoxia during pregnancy increases the risk of complications like preeclampsia and fetal growth restriction and has lasting effects on offspring, extending from infancy to adulthood. Understanding how chronic hypoxia alters physiological adaptations to pregnancy and pregnancy outcomes is essential for high-altitude populations and for gaining broader insights into the mechanisms underlying reduced fetoplacental oxygenation in complicated pregnancy at sea level. This review summarizes current knowledge on physiological adaptations during pregnancy under hypoxic conditions. We describe key studies on the effects of high altitude and chronic hypoxia on pregnancy, and examine the maternal, placental, fetal, and long-term physiological consequences. Finally, we review preclinical and clinical studies aimed at identifying interventions that could prevent or alleviate the adverse effects of chronic hypoxia on pregnancy outcomes and beyond.

Keywords:  DOHaD; Low oxygen; fetal development; gestation; placenta

DOI:  https://doi.org/10.1152/physrev.00003.2026
Ecotoxicol Environ Saf. 2026 Aug 14. pii: S0147-6513(26)00994-2. [Epub ahead of print]323 120664

Impairment of placental function and maternal-fetal immunity cross-talk by per- and polyfluoroalkyl substances during early pregnancy.

Yu Xia, Humblenoble Stembridge Ayuk, Oddvar Myhre, Ana Claudia Zenclussen, Violeta Stojanovska.

  Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants that have been associated with adverse pregnancy outcomes and immune dysfunction. However, the impact of PFAS on trophoblast-mediated immune interactions at the maternal-fetal interface remains unclear. In this study, we evaluated the effects of human-relevant PFAS on trophoblast function and immune crosstalk using a three-dimensional (3D) trophoblast spheroid model and a co-culture system with CD4+ T cells. JEG-3 spheroids were exposed to multiple PFAS, including perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), individually and as a mixture at real-life concentrations to assess viability, invasion and trophoblast-derived β-hCG secretion. Using a placental-immune cell co-culture model, we examined bidirectional interactions and their respective effects on functional endpoints in both cellular compartments and further investigated how exposure to PFAS may interfere in the bidirectional communication. We reported a significant decrease in trophoblast viability, after exposure to individual PFOS, PFOA and the PFAS mixture. PFAS mixture, PFOS, PFHxS, PFNA and PFDA exposure significantly increased invasiveness in JEG-3 spheroids, while PFOA decreased JEG-3 invasion significantly. Additionally, β-hCG production declined after 48 h of PFOS and PFAS mixture exposure in JEG-3 spheroids. Moreover, following PFAS mixture exposure, we observed a downregulation of CD69 and IFNγ production in CD4+ T cells, particularly within Th2 cells, while CD154 expression was also reduced. Overall, these findings suggest that PFAS exposure may influence trophoblast-mediated immune signaling, with potential implications for pregnancy-related processes.

Keywords:  CD4(+) T cells; Endocrine disrupting chemicals (EDCs); Maternal-fetal interface; PFAS; Trophoblast spheroids

DOI:  https://doi.org/10.1016/j.ecoenv.2026.120664
J Gen Virol. 2026 Aug;107(8):

Rift Valley fever virus infects trophoblast cell lines in an LRP1-dependent manner.

Rachael E Rush, David A Price, Cynthia M McMillen, David L Donermeyer, Daisy W Leung, Gaya K Amarasinghe, Amy L Hartman.

  Rift Valley fever virus (RVFV) is a mosquito-borne phlebovirus that poses a growing global threat, causing severe disease in humans and livestock, including hepatitis, haemorrhage and encephalitis. Documented cases of vertical transmission in humans and livestock highlight risks during pregnancy. Although RVFV can directly infect the placenta, how it enters trophoblast cells remains unclear. Here, we investigated the role of low-density lipoprotein receptor-related protein 1 (LRP1), a known RVFV entry factor, in human trophoblast infection. Using JEG-3, JAR and HTR-8/SVneo trophoblast cell lines, we demonstrate that RVFV replicates to high titres and LRP1 expression varies across cell types. Competitive inhibition assays using the high-affinity LRP1 ligand murine RAP domain 3 and recombinant LRP1 fragments (cluster proteins) indicate that RVFV requires LRP1 for efficient trophoblast infection. Together, these findings implicate LRP1 as a determinant of RVFV infection at the maternal-fetal interface.

Keywords:  CD91; LRP1; Rift Valley fever; bunyavirus; placenta; trophoblast

DOI:  https://doi.org/10.1099/jgv.0.002300
J Magn Reson Imaging. 2026 Aug 12.

Uteroplacental Responses to Physiological Challenges Throughout Pregnancy Using MRI.

Esra Abaci Turk, Neel Dey, Tiantian Lei, Henry A Feldman, Elfar Adalsteinsson, William H Barth, Polina Golland, P Ellen Grant.

   BACKGROUND: Placental MRI has shown T2* decreases during contractions and increases during maternal hyperoxia. However, how contraction-induced placental oxygenation and deformation relate to uterine deformation and differ from hyperoxia-induced responses remains unknown.
PURPOSE: To quantify placental T2* and deformation changes during spontaneous non-labor uterine contractions and maternal hyperoxia, testing the hypothesis that contractions produce mechanically mediated placental responses distinct from hyperoxia.
STUDY TYPE: Retrospective.
POPULATION: Forty-nine MRI datasets from 46 pregnant participants with singleton pregnancies (24-39 weeks gestation).
FIELD STRENGTH/SEQUENCE: 3 T; dynamic multi-echo gradient-echo echo-planar imaging.
ASSESSMENT: Non-labor uterine contractions were defined as events lasting ≥ 0.5 min with peak uterine volume reduction > 2.5%. Placental T2* and deformation of the uterus, myometrium, placenta, fetus and amniotic fluid were quantified during normoxia (normal air, 21% O2, 5 min) with and without contractions, and maternal hyperoxia (100% FiO2, 4 min). Regional analyses were performed within and outside imaging-defined placental cotyledons.
STATISTICAL TESTS: Linear regression, linear mixed-effects models, Pearson correlation and paired t-tests (p < 0.05).
RESULTS: Complete contractions during normoxia were identified in 22 datasets, reducing placental T2* by 4.64 ± 0.75 ms. Maternal hyperoxia increased placental T2* by 11.36 ± 0.62 ms relative to normoxia. Significant gestational age-by-duration interactions were observed for contraction-associated placental deformation (β = 2.47 ± 1.04% points/min/week) and T2* reduction (β = 1.50 ± 0.44 ms/min/week). At baseline, cotyledons exhibited higher T2* than surrounding placental tissue (β = -11.56 ± 0.95 ms). Contractions significantly reduced the inside-outside cotyledon T2* difference (β = 3.14 ± 1.34 ms), whereas hyperoxia preserved regional heterogeneity (p = 0.48).
DATA CONCLUSION: Spontaneous non-labor uterine contractions induced coordinated decreases in placental volume and oxygenation that intensified with gestational age and contraction duration. In contrast, maternal hyperoxia produced larger, more uniform increases in oxygenation.
EVIDENCE LEVEL: 3.
TECHNICAL EFFICACY: Stage 3.

Keywords:  T2*; hyperoxia; non‐labor uterine contraction; placenta

DOI:  https://doi.org/10.1002/jmri.70500
Biol Reprod. 2026 Aug 10. pii: ioag168. [Epub ahead of print]

PSG2 Impairs Human Trophoblast Function in Preeclampsia by Activating TGF-β/Smad3 to Suppress EMT and MMP2/9 Expression.

Yanping Qin, Shengping Meng, Siying Chen, Chunyan Lv, Chenguang Wang, Junyou Su, Chuzhen Lin, Yajuan Xu, Mengru Lin, Sumei Wang.

  Preeclampsia (PE) is a severe pregnancy-specific disorder featured by insufficient extravillous trophoblast (EVT) invasion and impaired spiral artery remodeling. Pregnancy-specific beta-1-glycoprotein 2 (PSG2), a placenta-derived protein, is significantly elevated in the serum of PE patients, yet its exact role and underlying mechanism in trophoblast function remain largely unknown. We demonstrated that PSG2 was remarkably upregulated in PE placentas and its expression correlated positively with blood pressure and proteinuria, and negatively with gestational age and birth weight. In HTR-8/SVneo trophoblast cells, PSG2 overexpression suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), downregulated MMP2 and MMP9 expression, and induced S-phase cell cycle arrest and late apoptosis. Conversely, PSG2 knockdown exerted opposing effects without influencing cell cycle distribution or apoptosis. Immunofluorescence staining verified the co-localization of PSG2 and TGF-β1 in trophoblasts and placental tissues. Mechanistically, PSG2 activated the TGF-β/Smad3 signaling pathway, and the TGFBR1 inhibitor SB431542 effectively reversed PSG2-mediated inhibition of EMT, MMP2/MMP9 expression, and trophoblast functional impairment. In conclusion, highly expressed PSG2 in PE placentas contributes to PE pathogenesis by activating the TGF-β/Smad3 pathway, thereby inhibiting EMT and MMPs expression and attenuating trophoblast proliferation, migration, and invasion. These findings provide a novel molecular basis for understanding PE pathogenesis.

Keywords:  PSG2; TGF-β/Smad3 signaling pathway; epithelial-mesenchymal transition; matrix metalloproteinases; preeclampsia

DOI:  https://doi.org/10.1093/biolre/ioag168
Exp Physiol. 2026 Aug 11.

Leptin-cholesterol crosstalk in pregnancy: Mechanistic implications for placental function and cardiometabolic programming.

Julio Flores, Diego Gumera, Andreina Arias, Cristián A Amador, María José Yañez.

  Pregnancy requires the coordinated maternal reorganization of lipid and endocrine pathways to sustain fetal growth and anticipate neonatal nutrition. Leptin, produced by adipose tissue and the placenta, acts as an integrative signal linking maternal energy status with trophoblast function and vascular adaptation, while cholesterol provides essential structural and hormonal substrates required for steroidogenesis and neurodevelopment. Emerging evidence indicates that leptin and cholesterol act as convergent regulators of metabolic and cardiovascular (CV) adaptation during pregnancy. We propose that excessive hyperleptinaemia and maternal hypercholesterolaemia, frequently coexisting, form a convergent axis that modulates placental signalling, alters the epigenetic regulation of lipid transporters and disrupts mitochondrial homeostasis. Mechanistically, this convergence operates through hepatic, epigenetic and renal pathways detailed throughout this review. Beyond the placenta, dysregulation of the leptin-cholesterol axis may extend to maternal organs central to CV homeostasis, particularly the kidney. Emerging evidence suggests that similar leptin-driven renal pathways may operate during pregnancy, amplifying vascular dysfunction and susceptibility to hypertensive complications. This perspective highlights the leptin-cholesterol axis as a mechanistic link connecting placental, kidney and CV pathways within the Developmental Origins of Health and Disease (DOHaD) paradigm, with potential implications for long-term cardiometabolic risk. This review integrates molecular, epigenetic and clinical evidence to emphasize lipoprotein-centred mechanisms, identify critical knowledge gaps and discuss translational opportunities for nutritional intervention, biomarker development and early-life preventive strategies.

Keywords:  PCSK9; cardiometabolic disease; cholesterol; hepatic LDL clearance; leptin; leptin resistance; lipoprotein metabolism; placenta; pregnancy

DOI:  https://doi.org/10.1113/EP093766
Toxicol Appl Pharmacol. 2026 Aug 13. pii: S0041-008X(26)00292-9. [Epub ahead of print]515 117996

Gestational inhalation of nanoparticles alters placental glucose transporter expression and increases glucose flux in rats.

Talia N Seymore, Sara Hoffmann, Pedro Louro, Carol Gardner, Michael J Goedken, Phoebe A Stapleton.

  Fetal health is heavily dictated by the maternal environment. Inhaling airborne pollutants, like particulate matter, is associated with pregnancy complications and fetal developmental pathologies, including fetal growth restriction (FGR). Because fetal growth is dependent on the placental transfer of nutrients from the maternal circulation, particularly glucose, investigating glucose transport capacity is critical to understanding the development of FGR associated with gestational inhalation of particulate matter. Pregnant Sprague Dawley rats were exposed to titanium dioxide nanoparticles (9.8 ± 1.0 mg/m3) to model occupational-level exposure to airborne particulates, from gestational day (GD) 5 to GD 19 via whole-body inhalation. Glucose transporters (GLUTs) 1, 3 and 4 were evaluated in term placentas on GD 20 and ex vivo placental perfusion was conducted as a functional assessment of glucose transport. Exposure resulted in a reduction in Glut3 mRNA and GLUT1 protein. However, exposed placentas exhibited a functional adaptation, characterized by increased GLUT4 expression and membrane localization of both GLUT1 and GLUT4. Placental perfusion confirmed these molecular changes, revealing increased glucose flux in exposed placentas compared to control (AUC 95% CI: 77.4 to 127.5 vs 39.1 to 73.6, respectively). Contrary to our hypothesis, exposure to these nanoparticles enhanced glucose transport across the placenta. Here we have demonstrated that inhaling airborne pollutants during pregnancy modulates placental function and nutrient transport mechanisms, which can have direct effects on fetal development. Furthermore, we provide evidence for targeted interventions, aimed at mitigating fetal developmental pathologies.

Keywords:  Fetal growth restriction; Glucose transport; Nanoparticles; Particulate matter; Placenta

DOI:  https://doi.org/10.1016/j.taap.2026.117996
Int J Mol Sci. 2026 Jul 25. pii: 6641. [Epub ahead of print]27(15):

Trophoblast Retrieval from the Cervix (TRIC) Across Early Gestation: A Multi-Method Assessment of Extravillous Trophoblast Recovery.

Kirim Hong, Hee Yeon Jang, Ji Eun Park, Sung Han Shim, Sung Shin Shim, You Jung Han, Soo Hyun Kim, Hee Jin Park, Dong Hyun Cha.

  Trophoblast retrieval from the cervix (TRIC) is a non-invasive approach that enables access to fetal-derived extravillous trophoblast (EVT) cells as early as the first trimester of pregnancy, offering a unique opportunity for early placental and fetal assessment. Although TRIC has been reported to be feasible between 5 and 20 weeks of gestation, systematic evaluation of EVT recovery across early gestation using complementary analytical approaches remains limited. This study aimed to provide a multi-method assessment of EVT recovery across early gestation. Endocervical samples were collected from 53 pregnant women between 5 and 19 weeks of gestation. EVT cells were isolated by immunomagnetic separation using human leukocyte antigen-G (HLA-G)-specific antibodies and assessed by β-hCG immunofluorescence, fluorescence in situ hybridization (FISH) and fluorescence-activated cell sorting (FACS). Immunofluorescence and FISH analyses showed no significant differences in β-hCG-positive or fetal cell proportions among gestational age groups, supporting stable TRIC-based recovery across early gestation. Exploratory FACS analyses identified HLA-G-positive trophoblast populations, including in samples obtained at 5 weeks of gestation. Because FACS analyses were performed in a subset of the cohort, these findings should be considered exploratory and require validation in larger cohort-wide studies. Overall, our findings support the feasibility of TRIC throughout early gestation and confirm the successful recovery of fetal-derived EVT cells from as early as 5 weeks of gestation. Further studies using larger cohorts and standardized quantitative approaches are required to more comprehensively characterize EVT recovery across early gestation and to optimize the application of TRIC in placental and prenatal research.

Keywords:  HLA-G; extravillous trophoblast; fluorescence-activated cell sorting (FACS); gestational age; placentation; prenatal diagnosis; trophoblast recovery; trophoblast retrieval from the cervix (TRIC)

DOI:  https://doi.org/10.3390/ijms27156641
Free Radic Biol Med. 2026 Aug 11. pii: S0891-5849(26)00999-8. [Epub ahead of print]255 744-762

Polystyrene nanoplastics induce fetal growth restriction via a novel NMNAT3 depletion cascade disrupting placental mitochondrial energetics and activating ferritinophagic ferroptosis.

Yijing He, Qinfeng Sun, Qianqian Yang, Hui Liu, Wenzhe Yang, Zhiyi Kong, Miaoyu Chen, Weihan Wang, Qiao Li, Shiqiang Ju.

  The escalating environmental prevalence of micro- and nanoplastics (NPs) poses a growing threat to maternal-fetal health, with the placenta being a particularly vulnerable interface. However, the precise metabolic mechanisms by which NPs compromise placental function and contribute to adverse pregnancy outcomes remain poorly understood. This study, employing untargeted metabolomics, reveals that gestational exposure to polystyrene nanoplastics (PS-NPs) severely disrupts placental nicotinamide (NAM) metabolism and impairs mitochondrial energetics. A key mechanistic discovery is the central role of NMNAT3, a mitochondrial NAD+ synthase. PS-NPs exposure downregulated NMNAT3, leading to NAD+ depletion, mitochondrial dysfunction, oxidative stress, and lipid peroxidation in trophoblasts, which collectively triggered ferritinophagy-mediated ferroptosis. Notably, NMNAT3 overexpression rescued these defects by suppressing ferritinophagy, limiting cytotoxic iron release, and inhibiting ferroptosis. Importantly, NAM, as a metabolic modulator, can inhibit ferroptosis and improve pregnancy outcomes by restoring NAD+ homeostasis. Collectively, our findings delineate a novel pathogenic axis wherein PS-NPs impair placental health via NMNAT3-dependent disruption of NAM metabolism and iron homeostasis, highlighting NAM supplementation as potential strategies to counteract nanoplastic-induced reproductive toxicity.

Keywords:  Ferroptosis; NAM metabolism; NMNAT3; Placenta; Polystyrene nanoplastics

DOI:  https://doi.org/10.1016/j.freeradbiomed.2026.08.010
Psychoneuroendocrinology. 2026 Aug 06. pii: S0306-4530(26)00248-9. [Epub ahead of print]193 107988

Glucocorticoids and placental 11βHSD2 - A systematic review of human studies and animal models.

Paula M Pfeiffer, Moumen M Alhasan, Deborah M Sloboda, Thorsten Braun, Sonja Entringer.

   CONTEXT: Elevated prenatal glucocorticoid (GC) exposure is linked to adverse offspring outcomes. The placental enzyme 11β-hydroxysteroid-dehydrogenase-type-2 (11βHSD2) protects the fetus by converting maternal derived cortisol to inactive cortisone. Although in vitro studies suggest GC mediated upregulation of 11βHSD2, in vivo evidence remains inconclusive.
METHODS: PubMed, Embase, and PsycInfo were searched in October 2024 for human and mammalian animal studies on endogenous or exogenous GCs during pregnancy and associations with placental 11βHSD2 (mRNA, protein, activity, gene methylation). Narrative synthesis was conducted due to heterogeneity precluding meta-analysis.
RESULTS: Eighteen studies (eight human, ten animal populations) met inclusion criteria. Exogenous GC exposure was associated with modifications in placental 11βHSD2 expression in animal models, with effects varying by substance, timing, and species. Dexamethasone trended towards increased expression in rodents, whereas betamethasone increased expression in non-human primates but not rodents. Human studies on endogenous GCs showed inconsistent associations with 11βHSD2 changes. In asthmatic pregnancies, moderate inhaled GC-use maintained enzyme activity compared to untreated patients. No convincing sex-specific trend emerged.
CONCLUSIONS: GC exposure alters placental 11βHSD2 in a substance- and species-specific way; translational relevance remains limited based on current literature. Future studies should employ technological advances and include GC-sensitive biomarkers to clarify mechanisms of maternal-fetal stress transmission.

Keywords:  11βHSD2; Fetal programming; Glucocorticoids; Placenta; Pregnancy; Systematic Review

DOI:  https://doi.org/10.1016/j.psyneuen.2026.107988
Neurobiol Stress. 2026 Sep;44 100839

Temporal reorganization of maternal care during early life stress in mice.

Hannah Jo, Eman Ali, Catherine Jensen Peña.

  Maternal separation is a widely used early-life stress (ELS) paradigm in rodents. Disrupted maternal care by separation of pups from the dam for several hours per day across neonatal and juvenile development has been found to alter hypothalamic-pituitary-adrenal axis function, molecular and circuit-level brain development and function, and behaviors associated with anxiety, depression, and cognition. However, dams have been found to temporarily increase their care towards pups upon reunion - typically associated with positive outcome measures - calling into question whether this increase in care compensates for care lost during separation. Using a mouse model of ELS, we quantified maternal home cage behaviors from postnatal day P2-16 across three observation periods per day (prior to maternal separation, immediately following reunion, and several hours following reunion), with maternal separation beginning on P10. Four composite variables of home cage behavior frequency were created: total dam-pup contact, rough contact, no contact, and dam self-care. Consistent with previous reports, we found a transient increase in care upon reunion, along with an increase in rough contact and a decrease in dam self-care. We then calculated geometric area-under-curve across the day and found that the increase in total contact among ELS litters does not result in overall more care, as indicated in previous publications, but rather a temporal reorganization of care. These findings provide important nuance to understand how maternal separation disrupts offspring care.

Keywords:  Early life adversity; Early-life stress; Maternal behavior; Maternal separation

DOI:  https://doi.org/10.1016/j.ynstr.2026.100839
EMBO J. 2026 Aug 10.

In-situ cryo-ET of mouse embryos reveals cytoplasmic lattices contain ubiquitin-charged E2-E3 ligase assemblies.

Kashish Singh, Katarina Harasimov, Kathy K Niakan, Andrew P Carter.

Cytoplasmic lattices (CPLs) are filamentous assemblies essential for mammalian embryonic development. They are known to regulate organelle organization, spindle assembly, and protein homeostasis, but their molecular functions remain unclear. Here, we develop a strategy combining cryo-focused ion beam milling and cryo-electron tomography to resolve macromolecular complexes directly in mammalian embryos. Using this approach, we determine the in situ structure of cytoplasmic lattices within 6/8-cell mouse embryos at ~4.7 Å resolution. CPL filaments are built from multiple copies of at least fourteen proteins arranged into a ~4.5 MDa repeating unit. The repeat contains a central cavity that is open at the back and lined with multiple FBXW-SKP1 complexes and three modules, each containing the E2 ubiquitin-conjugating enzyme UBE2D and the E3 ligase UHRF1. We resolve two CPL states: one is consistent with a ubiquitin-charged UBE2D, where ubiquitin is held in an open, inactive conformation by binding the scaffold protein PADI6; the second lacks discernible ubiquitin density and shows structural changes compatible with ubiquitin becoming available for transfer. Our findings support a model in which CPLs function as large ubiquitin ligase assemblies during early embryonic development.

DOI: https://doi.org/10.1038/s44318-026-00895-w
Dev Cell. 2026 Aug 13. pii: S1534-5807(26)00281-9. [Epub ahead of print]

Systematic differences in protein stability underlie species-specific developmental tempo.

Mitsuhiro Matsuda, Henrik M Hammarén, Jorge Lázaro, Mikhail M Savitski, Miki Ebisuya.

  Human embryonic development proceeds more slowly than in mice. The segmentation clock offers a tractable model for studying species-specific developmental tempo, as its oscillation period in human induced presomitic mesoderm (iPSM) cells is approximately twice that of mouse. While the core clock gene HES7 exhibits slower protein degradation in human cells, it remains unclear whether such cross-species differences in protein stability reflect a general principle. Here, we perform a dynamic stable isotope labeling of amino acids in cell culture (SILAC)-based proteomic analysis of ∼5,000 proteins in human and mouse iPSM, and we uncover a broad trend of slower protein degradation in human cells, regardless of subcellular localization or degradation pathways. Moreover, inhibition of glycolysis in mouse iPSM partially phenocopies the human protein stability profile, and modulation of protein stability alters the tempo of both the segmentation clock and cellular differentiation. Our findings establish protein stability, with systematic differences across species, as a key mediator linking metabolism to developmental tempo.

Keywords:  SILAC proteomics; allochrony; cross-species comparison; developmental tempo; metabolism; protein stability; segmentation clock

DOI:  https://doi.org/10.1016/j.devcel.2026.07.012