bims-placeb 2025-11-02 papers

bims-placeb

Biomed News

on Placental cell biology

Issue of 2025–11–02
fourteen papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences

Transcriptomic comparison of early onset preeclampsia and placenta accreta identifies inverse trophoblast and decidua functions at the maternal-fetal interface.
Comparative analysis of rhesus macaque and human placental organoids highlights evolutionary differences in placentation.
Maternal hypoxia exposure perturbs imprinted gene methylation in adult sperm and induces intergenerational placental impairments in male offspring.
TET1 modulates trophoblast function by regulation of ODC1 in preeclampsia.
RRS1 regulates proliferation, migration, and invasion of HTR-8/SVneo human trophoblasts.
Intrauterine oxygen milieu governs placental sphingolipid metabolism.
Bovine trophoblast-derived extracellular vesicles modulate the gene expression profile of peripheral leukocytes.
The monster villus: A rare, but characteristic, feature of human placentas in diabetes mellitus.
Phenotypic Alteration and Suppression of Cytotoxicity of Decidual NK Cells After Co-culturing With Different Trophoblastic Cell Lines.
Extracellular vesicles derived from placental trophoblast regulate ovine endometrial receptivity by promoting the transformation of endometrial epithelial cells.
Prenatal Dietary Exposure to Endocrine Disruptors and Its Lasting Impact on Offspring Health.
The role of mTOR signaling pathway-mediated Treg/Th17 cell imbalance in recurrent spontaneous abortion.
Birth weight-to-placental weight ratio and perinatal outcomes in gestational diabetes mellitus: a prospective cohort study at a university hospital in Bangkok, Thailand.
Irg1l regulates neuromast size via metabolic reprogramming to promote supporting cell proliferation.

NPJ Womens Health. 2025 ;3(1): 59

Transcriptomic comparison of early onset preeclampsia and placenta accreta identifies inverse trophoblast and decidua functions at the maternal-fetal interface.

Ophelia Yin, Ana Almonte-Loya, Romina Appierdo, Monica Yang, Bahar D Yilmaz, Tomiko T Oskotsky, Juan M Gonzalez-Velez, Linda C Giudice, Yalda Afshar, Marina Sirota.

  Early onset preeclampsia is a placental disorder characterized by shallow implantation, whereas placenta accreta spectrum is a placental disorder of deep placental attachment. This study compares the transcriptome of these two obstetric syndromes. By integrating available microarray and single-cell placenta/decidua transcriptomic datasets, we demonstrated that early onset preeclampsia genes are inversely expressed in placenta accreta, with the most marked differences noted in cell types of decidua, endothelial, and extravillous trophoblasts. Our findings highlight the key functions of trophoblast cell migration and invasion, decidua cell signaling, hypoxia pathways, and global growth factor and collagen contributions to these pregnancy disorders. This research provides new insights into the mechanisms of placentation and unifies these clinical siloes of disease by focusing on the fundamental biology of placental development at the maternal-fetal interface.

Keywords:  Health care; Reproductive biology

DOI:  https://doi.org/10.1038/s44294-025-00106-7
Dev Cell. 2025 Oct 30. pii: S1534-5807(25)00632-X. [Epub ahead of print]

Comparative analysis of rhesus macaque and human placental organoids highlights evolutionary differences in placentation.

Allyson Caldwell, Liheng Yang, Elizabeth A Scheef, Amitinder Kaur, Carolyn B Coyne.

  Throughout evolution, the placenta has diversified in structure and composition while maintaining its essential role in supporting fetal development. Trophoblasts, cells responsible for nutrient exchange and immune modulation, are a conserved feature of all placentas. Although primate placentas share morphological similarities, species-specific differences in gene expression remain poorly characterized, largely due to the lack of tractable in vitro models. To address this gap, we developed rhesus macaque placental organoids representing trophoblast and maternal-derived decidual cell types and compared them with human placental organoids. Using integrated single-cell and single-nucleus RNA sequencing, we identified shared and species-specific transcriptional programs across corresponding trophoblast lineages. We further reconstructed lineage trajectories to multinucleated syncytiotrophoblast and extravillous trophoblast populations, revealing conserved differentiation pathways alongside divergent gene expression signatures. This work establishes in vitro models of the nonhuman primate placenta and defines molecular distinctions between human and rhesus trophoblasts, offering insights into evolutionary adaptations underlying placental development.

Keywords:  bulk RNA sequencing; bulk RNA-seq; decidua organoid; placenta; rhesus macaque; scRNA-seq; single-cell RNA sequencing; single-nucleus RNA sequencing; snRNA-seq; trophoblast; trophoblast organoid

DOI:  https://doi.org/10.1016/j.devcel.2025.10.002
Zool Res. 2025 Nov 18. pii: 2095-8137(2025)06-1273-16. [Epub ahead of print]46(6): 1273-1288

Maternal hypoxia exposure perturbs imprinted gene methylation in adult sperm and induces intergenerational placental impairments in male offspring.

Lu-Yao Zhang, Gong-Xue Jia, Hai-Ping Tao, Ke-Xiong Liu, Yu-Wen Luo, Yun-Peng Hou, Qi-En Yang.

  Hypobaric hypoxia encountered at high altitudes impairs reproductive health and fertility across species. Previous findings have demonstrated that maternal hypoxia exposure disrupts granulosa cell (GC) viability and oocyte maturation in female offspring; however, its transgenerational impact on male reproductive outcomes remains poorly elucidated. In this study, pregnant mice (F0) were subjected to hypoxic conditions, and male progeny across four generations (F1‒F4) were evaluated. Results revealed that maternal hypoxia induced mild alterations in sperm DNA methylation in F1 males but caused profound developmental defects in F2 embryos, predominantly affecting males. Following mating of F1 males with control females, a substantial proportion of male F2 fetuses were lost at embryonic day (E) 13.5, attributed to placental malformations. Integrated RNA sequencing and whole-genome bisulfite sequencing of placentas from male fetuses revealed aberrant expression of imprinted genes, including Gnas, Slc38a4, Jade1, and Kcnq1, which also exhibited differential methylation in F1 sperm. These findings demonstrate that maternal hypoxia disrupts epigenetic programming in F1 germ cells, impairing placental development and fetal viability in F2 males, thereby leading to an unbalanced sex ratio. Overall, this study elucidates the mechanisms by which environmental hypoxia influences sex ratios and offers critical insights into hypoxia-induced reproductive impairments in mammals.

Keywords:  DNA methylation; Imprinted genes; Maternal hypoxia; Placenta; Sex ratio

DOI:  https://doi.org/10.24272/j.issn.2095-8137.2025.031
Sci Rep. 2025 Oct 31. 15(1): 38208

TET1 modulates trophoblast function by regulation of ODC1 in preeclampsia.

Chao Fan, Yan Kang, Zhenya Fang, Lixia Liu, Chunying Wang, Man Zhao, Li Xiao, Changqing Zhang.

  Preeclampsia (PE) is a pregnancy-specific disease that seriously endangers the health of the pregnant woman and the fetus. DNA hydroxymethylation, an epigenetic modification, plays crucial roles in the development of PE. However, the molecular mechanism remains to be elucidated. TET1 is a DNA demethylase that regulates placental trophoblast function. Herein, we investigated the role of TET1 in PE occurrence. Firstly, we confirmed that the 5-methylcytosine (5-mC) levels were reduced in placental tissues from human PE patients and a mouse PE model, while TET1 expression was upregulated. In an oxidative stress model of HTR8/SVneo cells, knockdown of TET1 partially restored the impaired cell invasion and migration caused by H2O2. To elucidate the mechanism, bioinformatics analysis of TET1-knockdown RNA sequencing and ChIP-seq data identified ornithine decarboxylase (ODC1), a rate-limiting enzyme in the polyamine biosynthesis, as a potential target. Similarly, knockdown of ODC1 alleviated the H2O2-induced dysfunction in HTR8/SVneo cells. Moreover, the CUT&RUN and dual-luciferase assays revealed that TET1 regulates the expression of ODC1 by affecting the methylation level of its promoter. Collectively, these results demonstrate that TET1-mediated DNA hydroxymethylation is associated with the occurrence of PE. This is partially attributed to the regulation of ODC1 through altered promoter methylation, which leads to trophoblast dysfunction and contributes to the development of PE.

Keywords:  DNA hydroxymethylation; ODC1; Preeclampsia; TET1; Trophoblast

DOI:  https://doi.org/10.1038/s41598-025-22116-w
Front Med. 2025 Oct;19(5): 831-841

RRS1 regulates proliferation, migration, and invasion of HTR-8/SVneo human trophoblasts.

Yixuan Wu, Yao Li, Jing Wang, Qianying Guo, Wei Chen, Jie Qiao, Liying Yan, Peng Yuan.

  Trophoblast cells serve as the foundation for placental development. We analyzed published multiomics sequencing data and found that trophoblast cells highly expressed RRS1 compared to primitive endoderm and epiblast. We used HTR-8/SVneo cells for further investigation, and Western blot and immunofluorescence staining confirmed that HTR-8/SVneo cells highly expressed RRS1. RRS1 was successfully knocked down in HTR-8/SVneo cells using siRNA. Using IncuCyte S3 live-cell analysis system based on continuous live-cell imaging and real-time data, we observed that proliferation, migration, and invasion abilities were all significantly decreased in RRS1-knockdown cells. RNA-seq revealed that knockdown of RRS1 affected the gene transcription, and upregulated pathways in extracellular matrix organization, DNA damage response, and intrinsic apoptotic signaling, downregulated pathways in embryo implantation, trophoblast cell migration, and wound healing. Differentially expressed genes were enriched in diseases related to placental development. Consistent with these findings, human chorionic villus samples collected from spontaneous abortion cases exhibited significantly reduced RRS1 expression compared to normal controls. Our results highlight the functional importance of RRS1 in human trophoblasts and suggest that its deficiency contributes to early pregnancy loss.

Keywords:  HTR-8/SVneo cells; RNA-seq; live-cell analysis; spontaneous abortion; trophoblast cell

DOI:  https://doi.org/10.1007/s11684-025-1150-6
J Lipid Res. 2025 Oct 28. pii: S0022-2275(25)00193-2. [Epub ahead of print] 100930

Intrauterine oxygen milieu governs placental sphingolipid metabolism.

Julien Sallais, Martin Post, Isabella Caniggia.

  Early placentation relies on temporal changes in intrauterine oxygen tension that regulate trophoblast differentiation events. Studies have highlighted the contribution of bioactive sphingolipids to the pathogenesis of placental disorders, characterized by hypoxia. However, it is unknown whether placental sphingolipid metabolism changes during the switch from a hypoxic to an oxygenated environment in the first trimester of gestation and if sustained hypoxia is causative of sphingolipid alterations seen in preeclampsia. Herein, we performed sphingolipid analysis of first-trimester human placentae as well as placentae from conditional (placenta-specific) Phd2 knockout mice (Phd2-/- cKO) that exhibit preeclampsia-like features, including placental hypoxia. Analysis revealed elevated long chain ceramide (Cer16:0, Cer18:0, Cer20:0 and Cer22:0) and reduced sphingosine-1-phosphate (So-1-P) content in Phd2-/- cKO placentae. Expression of key regulatory sphingolipid enzymes, acid ceramidase (ASAH1) and sphingosine kinase 1 (SPHK1), was reduced in Phd2-/- cKO placentae, while that of alkaline ceramidase ACER2 remained unchanged. Human placentae from 5-9 weeks of gestation, when intrauterine oxygen tension is low, exhibited heightened long chain ceramide (Cer14:0, Cer16:0, Cer18:0, Cer 18:1) and sphingosine content and reduced ASAH1and SPHK1 expression, highlighting the relevance of low oxygen in regulating sphingolipid metabolism under physiological (placental development) and pathological (Phd2-/- cKO induced preeclampsia) conditions. Ultrastructural analyses of early (5-9 weeks) human and murine Phd2-/- cKO placentae revealed that increased trophoblast mitochondrial fission events accompanied elevated ceramide. Together, the data support the concept that a chronic low-oxygen environment leads to placental ceramide buildup, which may alter mitochondrial homeostasis and potentially contribute to cell death events characteristic of preeclampsia.

Keywords:  Placenta; mitochondrial dynamics; oxygen; sphingolipids; trophoblast

DOI:  https://doi.org/10.1016/j.jlr.2025.100930
Anim Reprod Sci. 2025 Oct 24. pii: S0378-4320(25)00264-7. [Epub ahead of print]283 108025

Bovine trophoblast-derived extracellular vesicles modulate the gene expression profile of peripheral leukocytes.

Heloisa M Rutigliano, Amber E Thornton, Kira P Morgado, John R Stevens, Irina A Polejaeva, Christopher J Davies.

  This study aimed to determine whether trophoblast-derived extracellular vesicles (EVs) alter the gene expression and secretion profiles of inflammatory mediators in circulating leukocyte populations. Circulating leukocyte populations (CD14+, CD4+CD25-, CD4+CD25+, CD8+, and TCR-γδ+ cells) were exposed to either isolated bovine trophoblast-derived EVs (tEV), EV-free trophoblast cell culture supernatant (nEV), or whole trophoblast culture supernatant (wSP) and their transcription level and secretion of immune mediators was assessed. Extracellular vesicle concentrations measured by nanoparticle tracking analysis in the nEV, tEV, and wSP treatments were 1.78 × 10⁸, 9.81 × 10⁸, and 3.22 × 10⁸ particles/mL, respectively. Scanning electron microscopy confirmed the presence and morphology of EVs, which ranged in diameter from 25 to 308 nm, with most particles falling between 72 and 134 nm. Trophoblast-derived EVs significantly altered gene expression in multiple immune cell populations, including CD8⁺ cytotoxic T cells, CD4⁺CD25⁻ resting T helper cells, and CD4⁺CD25⁺ activated T helper cells. In CD8⁺ cells, tEVs upregulated IL13 and showed trends toward increased FOXP3 and IL23 expression. CD4⁺CD25⁻ cells treated with tEVs exhibited increased IL6 and trends toward reduced IL1B and IL13, while CD4⁺CD25⁺ cells showed elevated CXCL8 and tendencies for higher IL10, IFNG, and TNFA expression. No significant changes in gene expression were observed in TCR-γ/δ⁺ cells across treatments. Trophoblast-derived EVs decreased the secretion of CCL4 and NCAM1. Trophoblast-derived EVs contain miRNAs and proteins involved in many biological processes including cell proliferation, stem cell biology, cell migration, and immune response. Among proteins were the EV markers and trophoblast markers.

Keywords:  Extracellular vesicles; Immune; Leukocytes, Bovine pregnancy; Maternal-fetal interface; Placenta

DOI:  https://doi.org/10.1016/j.anireprosci.2025.108025
Placenta. 2025 Oct 28. pii: S0143-4004(25)00727-1. [Epub ahead of print]172 89-99

The monster villus: A rare, but characteristic, feature of human placentas in diabetes mellitus.

Berthold Huppertz, Marina Ivanisevic, Gernot Desoye.

   CONTEXT: Villous tree development of the human placenta is mostly driven by spatial organization of vessels. Diabetes in pregnancy is associated with structural alterations of the placenta, including hypervascularization of terminal villi.
OBJECTIVE: To assess pathological alterations of villous tree formation in cases with gestational diabetes (GDM) and type 1 diabetes mellitus (T1D) and alteration-associated maternal and fetal traits.
DESIGN: Placentas (n = 5 per group) from GDM treated with diet or insulin, from T1D without and with additional pathologies and from healthy term controls were stained with H&E and for CD34, desmin, vimentin and smooth-muscle actin to assess villous architecture and vascular patterns. Maternal and cord blood glucose and cord blood C-peptide (insulin proxy) were measured. In women with T1D, maternal glycosylated hemoglobin was determined in each trimester.
RESULTS: Only in cases with T1D and additional pathologies, chorangiosis and a distinct structural organization of the villous tree, called monster villus, were identified. Diameters of these monster villi were significantly higher compared to normal villi or those with chorangiosis. Monster villus features did not significantly associate with any trait, but two extreme cases with monster villi had the highest cord blood C-peptide levels.
CONCLUSIONS: Presence of paw-shaped stem villi branching into multiple functional villi, i.e. monster villi, may indicate the missing switch from branching to non-branching angiogenesis during villous development at 26-28 weeks of gestation. This specific morphological and vascular arrangement of the villous tree only occurred in cases with T1D and additional pathologies, conditions with elevated fetal insulin.

Keywords:  Angiogenesis; Morphology; Terminal villi; diabetes

DOI:  https://doi.org/10.1016/j.placenta.2025.10.019
Anticancer Res. 2025 Nov;45(11): 4717-4727

Phenotypic Alteration and Suppression of Cytotoxicity of Decidual NK Cells After Co-culturing With Different Trophoblastic Cell Lines.

Kornél F Lakatos, Kevin M Elias, Kathleen Hasselblatt, György L Végh, Thomas McElrath, Ross S Berkowitz, Vilmos Fülöp.

   BACKGROUND/AIM: Successful conception and pregnancy require a complex and organized communication between the embryo (allograft) and the mother's (host) immune system. The decidual NK cells (dNK), among other leukocyte subsets, have an important role in orchestrating this immune environment. This study aimed to investigate how exposure to benign and malignant trophoblastic cell lines affects the phenotype and cytotoxic function of dNK cells.
MATERIALS AND METHODS: In our study, we isolated dNK cells from term, healthy human placentas and sorted them to achieve a pure, CD56 bright, CD16 negative population. These NK cells were co-cultured with HTR-8 (benign) and Jeg-3 (malignant) trophoblastic cell lines for one and five days. The NK cells were isolated again after the exposure to the trophoblastic cells, and their phenotype was assessed again. Their cytotoxicity was also measured and compared to the cytotoxicity of dNK cells not exposed to trophoblastic cells.
RESULTS: After one day of co-culture, dNK phenotype remained unchanged with both cell lines. However, a five-day exposure to Jeg-3 cells resulted in a shift toward a CD56 diminished CD16+ phenotype, resembling peripheral NK cells. Additionally, cytotoxic activity of dNK cells was significantly reduced after co-culture with both cell lines, with a more pronounced suppression observed following exposure to Jeg-3 cells.
CONCLUSION: There are certain similarities between the immune evasion of tumor cells and the physiological invasion of the trophoblastic cells of embryonic origin into the maternal decidua. Understanding the ways of interaction between dNK cells and the trophoblastic cells may reveal similar immunological interactions between the host's NK cells and tumor cells.

Keywords:  Decidual NK cells; co-culturing; phenotypic changes; suppression of cytotoxicity; trophoblastic cells

DOI:  https://doi.org/10.21873/anticanres.17821
Reprod Biol. 2025 Oct 27. pii: S1642-431X(25)00098-1. [Epub ahead of print]26(1): 101091

Extracellular vesicles derived from placental trophoblast regulate ovine endometrial receptivity by promoting the transformation of endometrial epithelial cells.

Huijia Jin, Yujiao Guo, Yanshe Xie, Xin Xiang, Zhengguang Wang, Jizhong Xiang.

  The establishment of endometrial receptivity is required for successful embryo implantation during early pregnancy in many mammals. Extracellular vesicles (EVs) microRNAs (miRNAs) play an important role during embryo implantation. While their roles have been characterized in other species, the specific functions of trophoblast-derived EVs miRNAs in ovine endometrial receptivity remain undefined. In this study, we systematically investigated the effects of ovine placental trophoblast (OTR) cells-derived EVs on ovine endometrial epithelial cells (EECs) by cck-8 assay, EdU assay, cell migration assay, RT-qPCR and ultrastructural examination of apical plasma membranes. Subsequently, miRNA expression profiles of EV-treated EECs were identified and analyzed by miRNA-Seq. The results showed that OTR cells-derived EVs were taken up by EECs, enhancing the migration of EECs. EVs treatment reduced microvilli on the apical plasma membranes of EECs. The expression of genes involved in endometrial receptivity increased. OTR cells-derived EVs induced changes consistent with a receptive phenotype through coordinated cellular remodeling and gene expression changes. The miRNA-Seq results revealed 287 detectable miRNAs, including 34 with significant differential expression (20 upregulated and 14 downregulated) in EV-treated versus control EECs. The predicted target genes of these differentially expressed miRNAs were enriched in signaling pathways regulating embryo implantation and endometrial receptivity, such as MAPK, Toll-like receptor, adherens junction and focal adhesion. Our in vitro findings suggested that OTR cells-derived EVs may promote endometrial receptivity by facilitating the transformation of EECs, as indicated by receptivity-associated morphological and molecular changes. It provided novel insights for improving successful pregnancy rate in sheep.

Keywords:  Endometrial epithelial cells; Endometrial receptivity; Extracellular vesicles; MicroRNAs; Ovine placental trophoblast cells

DOI:  https://doi.org/10.1016/j.repbio.2025.101091
Toxics. 2025 Oct 11. pii: 864. [Epub ahead of print]13(10):

Prenatal Dietary Exposure to Endocrine Disruptors and Its Lasting Impact on Offspring Health.

Anastasios Potiris, Nikoletta Daponte, Efthalia Moustakli, Athanasios Zikopoulos, Eriketi Kokkosi, Nefeli Arkouli, Ismini Anagnostaki, Aikaterini Lydia Vogiatzoglou, Maria Tzeli, Angeliki Sarella, Ekaterini Domali, Sofoklis Stavros.

  Environmental stressors during the crucial period of fetal development can have a substantial impact on long-term health outcomes. A major concern is dietary exposure to endocrine-disrupting chemicals (EDCs), which can readily cross the placenta and disrupt fetal hormonal signaling and developmental programming. Examples of these chemicals include bisphenols, phthalates, pesticides, and persistent organic pollutants (POPs). Prenatal exposure to EDC has been associated with long-term effects in children, including immune disruption, metabolic dysregulation, impaired neurodevelopment, and reproductive alterations, as evidenced by human cohort studies and experimental models. Epigenetic reprogramming, direct interference with endocrine signaling, and oxidative stress (OS) are hypothesized pathways for these adverse consequences, which often combine to produce long-lasting physiological changes. This narrative review summarizes current research on maternal dietary exposure to EDCs during pregnancy, highlighting associations with adverse child health outcomes. It also discusses the growing evidence of transgenerational effects, the potential mechanisms linking prenatal exposure to long-term outcomes, and the importance of understanding the roles of timing, dosage, and chemical type. By highlighting the necessity of focused interventions to lower maternal EDC exposure and lessen threats to the health of offspring, the review concludes by discussing implications for future research, preventive measures, and public health policy.

Keywords:  developmental origins of health and disease (DOHaD); endocrine disruptors; maternal diet; offspring health; prenatal exposure

DOI:  https://doi.org/10.3390/toxics13100864
J Reprod Immunol. 2025 Oct 19. pii: S0165-0378(25)00322-5. [Epub ahead of print]172 104744

The role of mTOR signaling pathway-mediated Treg/Th17 cell imbalance in recurrent spontaneous abortion.

Yihong Chen, Leiyi Jin, Bei Gan, Shan Zheng, Xiumei Zhao, Juanbing Wei.

  Recurrent Spontaneous Abortion (RSA) is a significant clinical issue that affects many women, yet its underlying mechanisms remain poorly understood. Recent evidence suggests that immune dysregulation, particularly the imbalance between regulatory T cells (Treg) and T helper 17 cells (Th17), may play a critical role in this condition. In this study, we investigate the role of the mTOR signaling pathway in mediating Treg/Th17 cell imbalance in a RSA mouse model established by mating CBA female mice with DBA/2 male mice. The results demonstrate a significant increase in embryo loss rates in the miscarriage group compared to the normal pregnancy group, accompanied by placental damage and an immune imbalance characterized by decreased Treg and increased Th17 cell populations. Furthermore, Enzyme-Linked Immunosorbent (ELISA) assays reveal elevated levels of pro-inflammatory cytokines IL-17, along with reduced anti-inflammatory cytokines TGF-β and IL-10 in the serum of miscarriage mice. To elucidate the role of mTOR, we administered Metformin and Programmed Death-Ligand 1 Fc fusion protein (PD-L1 Fc fusion protein), which significantly improved pregnancy outcomes by restoring the Treg/Th17 ratio and reducing pro-inflammatory cytokine levels. Western blot and qRT-PCR analysis indicated that treatment reduced the expression of mTOR, HIF-1α, ROR-γt, and STAT3, suggesting that both therapies effectively correct Treg/Th17 cell imbalance by inhibiting mTOR signaling. Overall, our findings underscore the importance of mTOR signaling in the Treg/Th17 imbalance associated with RSA, providing new insights for potential therapeutic strategies.

Keywords:  RSA; Treg/Th17 cell; mTOR signaling pathway

DOI:  https://doi.org/10.1016/j.jri.2025.104744
BMJ Open. 2025 Oct 29. 15(10): e104482

Birth weight-to-placental weight ratio and perinatal outcomes in gestational diabetes mellitus: a prospective cohort study at a university hospital in Bangkok, Thailand.

Chadakarn Phaloprakarn, Chutima Chavanisakun, Petcharat Jenkumwong, Sasiwan Suthasmalee, Siriwan Tangjitgamol.

   OBJECTIVES: To compare birth weight-to-placental weight (BW:PW) ratios between pregnancies complicated by gestational diabetes mellitus (GDM) and normoglycaemic pregnancies, and to evaluate the associations between BW:PW ratio, perinatal outcomes, and placental histopathologic features within the GDM group.
DESIGN: A prospective cohort study.
SETTING: A university hospital in Bangkok, Thailand.
PARTICIPANTS: A total of 200 women with GDM and 100 normoglycaemic controls.
OUTCOME MEASURES: BW:PW ratios were calculated and compared between the two groups. Participants with GDM were stratified into three categories based on the BW:PW ratio percentiles: <10th, 10th-90th and >90th. Perinatal outcomes and placental histological abnormalities were analysed across these categories.
RESULTS: Median BW:PW ratios were not significantly different between the GDM and normoglycaemic groups: 6.3 (IQR 5.6 to 6.9) versus 6.2 (IQR 5.6 to 6.8); p=0.399. Within the GDM cohort, the BW:PW ratio cut-offs corresponding to the 10th and 90th percentiles were 5.2 and 7.6, respectively. The prevalence of small-for-gestational-age (SGA) neonates differed significantly among the three BW:PW ratio groups: 14.3% (<10th), 1.3% (10th-90th) and 4.5% (>90th); p=0.004. Similarly, the prevalence of chorangiosis varied significantly across these groups (66.7%, 52.9% and 22.7%, respectively; p=0.009). A BW:PW ratio <10th percentile was associated with an increased risk of SGA neonates (adjusted OR (aOR) 9.94; 95% CI 1.14 to 86.80), while a ratio >90th percentile was associated with reduced odds of chorangiosis (aOR 0.35; 95% CI 0.11 to 0.85).
CONCLUSIONS: BW:PW ratios did not differ significantly between the GDM and normoglycaemic groups. However, in GDM pregnancies, extremes in the BW:PW ratio were associated with distinct perinatal and placental outcomes, indicating altered placental efficiency and potential clinical relevance.
TRIAL REGISTRATION NUMBER: TCTR20211122001.

Keywords:  Diabetes in pregnancy; OBSTETRICS; Pregnancy

DOI:  https://doi.org/10.1136/bmjopen-2025-104482
J Cell Biol. 2025 Dec 01. pii: e202501122. [Epub ahead of print]224(12):

Irg1l regulates neuromast size via metabolic reprogramming to promote supporting cell proliferation.

Xin Wang, Ruijun Shi, Yuqing Xiang, Yajing Gao, Guoqiang Wan, Shan Sun, Dong Liu.

One of the most basic principles in embryonic development is ensuring the proper size of tissues and organs to meet functional needs. So far, an endogenous metabolite regulating organ size has not been described. The current study highlights itaconate, the product of Irg1, in regulating zebrafish neuromast size. Single-cell transcriptomic sequencing analysis of enzymes catalyzing metabolic processes revealed that irg1l, a homolog of Irg1, is highly expressed in supporting cells of developing neuromast in zebrafish. Deficiency of irg1l reduced the size of the neuromast and caused auditory dysfunction. Conversely, overexpression of irg1l resulted in increased size due to excessive proliferation of supporting cells. Notably, 4-octyl itaconate (4-OI), an itaconate derivative, treatment recapitulates the phenotype of irg1l overexpression and increases the neuromast size. Finally, we revealed that the Irg1l/itaconate axis induces metabolic reprogramming to promote activation of the Yap, drive supporting cell proliferation, and enlarge neuromast size. These findings provide a novel insight into the role of metabolites in organ development.

DOI: https://doi.org/10.1083/jcb.202501122