ArticleThe Journal of biological chemistry2015
Sphingolipid pathway regulates innate immune responses at the fetomaternal interface during pregnancy.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Ezrin, radixin, and moesin are novel citrullinated proteins in the decidua during pregnancy†.Biology of reproduction · 2026Article
- Proteomic profiling of porcine seminal extracellular vesicles reveals potential in vivo fertility biomarkers.Andrology · 2026Article
- Prenatal Organophosphate Pesticide Exposure and Targeted Maternal Pregnancy Metabolomic Profiles in the NYU CHES Cohort.Environmental science & technology · 2025Article
- Dyslipidemia and female reproductive failures: perspectives on lipid metabolism and endometrial immune dysregulation.Seminars in immunopathology · 2025Review
- Distinct Changes in Placental Ceramide Metabolism Characterize Type 1 and 2 Diabetic Pregnancies with Fetal Macrosomia or Preeclampsia.Biomedicines · 2023Article
- Lipidomic Analysis of Cervicovaginal Fluid for Elucidating Prognostic Biomarkers and Relevant Phospholipid and Sphingolipid Pathways in Preterm Birth.Metabolites · 2023Article
- c-Myc Drives inflammation of the maternal-fetal interface, and neonatal lung remodeling induced by intra-amniotic inflammation.Frontiers in cell and developmental biology · 2023Article
- Gestationally dependent immune organization at the maternal-fetal interface.Cell reports · 2022Article
- Spatiotemporal endometrial transcriptome analysis revealed the luminal epithelium as key player during initial maternal recognition of pregnancy in the mare.Scientific reports · 2021Article
- Maternal and fetal alkaline ceramidase 2 is required for placental vascular integrity in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Evaluation of different commercial antibodies for their ability to detect human and mouse tissue factor by western blotting.Research and practice in thrombosis and haemostasis · 2020Article
- The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth.International journal of molecular sciences · 2020Article
- Urinary Metabolites Altered during the Third Trimester in Pregnancies Complicated by Gestational Diabetes Mellitus: Relationship with Potential Upcoming Metabolic Disorders.International journal of molecular sciences · 2019Article
- CXCR2 Blockade Mitigates Neural Cell Injury Following Preclinical Chorioamnionitis.Frontiers in physiology · 2019Article
- The role of natural killer cells in the uterine microenvironment during pregnancy.Cellular & molecular immunology · 2018Article
- Gestational Diabetes Alters the Metabolomic Profile in 2nd Trimester Amniotic Fluid in a Sex-Specific Manner.International journal of molecular sciences · 2018Article
- Endogenous annexin A1 (AnxA1) modulates early-phase gestation and offspring sex-ratio skewing.Journal of cellular physiology · 2018Article
- Sphingolipids in neutrophil function and inflammatory responses: Mechanisms and implications for intestinal immunity and inflammation in ulcerative colitis.Advances in biological regulation · 2017Review
- Neutrophil migration into the placenta: Good, bad or deadly?Cell adhesion & migration · 2016Review
- Cellular Regulation of the Uterine Microenvironment That Enables Embryo Implantation.Frontiers in immunology · 2015Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For a successful pregnancy, the mother's immune system has to tolerate the semiallogeneic fetus. A deleterious immune attack is avoided by orchestration of cellular, hormonal, and enzymatic factors. However, the precise mechanisms underlying fetomaternal tolerance are not yet completely understood. In this study, we demonstrate that sphingolipid metabolism constitutes a novel signaling pathway that is indispensable for fetomaternal tolerance by regulating innate immune responses at the fetomaternal interface. Perturbation of the sphingolipid pathway by disruption of the sphingosine kinase gene (Sphk) during pregnancy caused unusually high expression of neutrophil chemoattractants, CXCL1 and CXCL2, in the decidua, leading to a massive infiltration of neutrophils into the fetomaternal interface with enhanced oxidative damage, resulting in early fetal death. Sphk-deficient mice also exhibited neutrophilia in the peripheral blood, enhanced generation of granulocytes in the bone marrow, and a decrease in the number of decidual natural killer cells. The blockage of neutrophil influx protected Sphk-deficient mice against pregnancy loss. Notably, a similar result was obtained in human decidual cells, in which Sphk deficiency dramatically increased the secretion of CXCL1 and IL-8. In conclusion, our findings suggest that the sphingolipid metabolic pathway plays a critical role in fetomaternal tolerance by regulating innate immunity at the fetomaternal interface both in mice and humans, and it could provide novel insight into the development of therapeutic strategies to treat idiopathic pregnancy loss in humans.
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