ArticleThe Journal of clinical investigation2015
Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 84 citations in OpenAlex.
- Effector and Activated T Cells Induce Preterm Labor and Birth That Is Prevented by Treatment with Progesterone.Journal of immunology (Baltimore, Md. : 1950) · 2019Trial
- Immunological maladaptation preceding spontaneous preterm birth in human pregnancies.Nature communications · 2026Article
- Effects of the gut microbiota on placental angiogenesis and intrauterine growth in gnotobiotic mice.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pregnancy-acquired memory CD4Nature communications · 2025Article
- CD4+ but not CD8+ T cells are required for protection against severe guinea pig cytomegalovirus infections.PLoS pathogens · 2024Article
- Beyond defence: Immune architects of ovarian health and disease.Seminars in immunopathology · 2024Review
- Review
- Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model.Journal of animal science and biotechnology · 2023Article
- Aire drives steroid hormone biosynthesis by medullary thymic epithelial cells.Science immunology · 2023Article
- The effects of progesterone on immune cellular function at the maternal-fetal interface and in maternal circulation.The Journal of steroid biochemistry and molecular biology · 2023Review
- Immune Tolerance of Embryo Implantation and Pregnancy: The Role of Human Decidual Stromal Cell- and Embryonic-Derived Extracellular Vesicles.International journal of molecular sciences · 2022Review
- Regulatory T Cell Proportion and Phenotype Are Altered in Women Using Oral Contraception.Endocrinology · 2022Article
- Effects of sex steroids on thymic epithelium and thymocyte development.Frontiers in immunology · 2022Review
- Inefficient Placental Virus Replication and Absence of Neonatal Cell-Specific Immunity Upon Sars-CoV-2 Infection During Pregnancy.Frontiers in immunology · 2021Observational
- The New Old CD8+ T Cells in the Immune Paradox of Pregnancy.Frontiers in immunology · 2021Review
- Disruption of Glucocorticoid Action on CD11cFrontiers in immunology · 2021Article
- Progesterone, via yes-associated protein, promotes cardiomyocyte proliferation and cardiac repair.Cell proliferation · 2020Article
- Stress, Sex, and Sugar: Glucocorticoids and Sex-Steroid Crosstalk in the Sex-Specific Misprogramming of Metabolism.Journal of the Endocrine Society · 2020Review
- Autoimmune Hepatitis: Tolerogenic Immunological State During Pregnancy and Immune Escape in Post-partum.Frontiers in immunology · 2020Review
- Developmental origin and sex-specific risk for infections and immune diseases later in life.Seminars in immunopathology · 2019Review
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 5 countries.
Funding
Abstract
Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies in Western societies. IUGR is a strong predictor of reduced short-term neonatal survival and impairs long-term health in children. Placental insufficiency is often associated with IUGR; however, the molecular mechanisms involved in the pathogenesis of placental insufficiency and IUGR are largely unknown. Here, we developed a mouse model of fetal-growth restriction and placental insufficiency that is induced by a midgestational stress challenge. Compared with control animals, pregnant dams subjected to gestational stress exhibited reduced progesterone levels and placental heme oxygenase 1 (Hmox1) expression and increased methylation at distinct regions of the placental Hmox1 promoter. These stress-triggered changes were accompanied by an altered CD8+ T cell response, as evidenced by a reduction of tolerogenic CD8+CD122+ T cells and an increase of cytotoxic CD8+ T cells. Using progesterone receptor- or Hmox1-deficient mice, we identified progesterone as an upstream modulator of placental Hmox1 expression. Supplementation of progesterone or depletion of CD8+ T cells revealed that progesterone suppresses CD8+ T cell cytotoxicity, whereas the generation of CD8+CD122+ T cells is supported by Hmox1 and ameliorates fetal-growth restriction in Hmox1 deficiency. These observations in mice could promote the identification of pregnancies at risk for IUGR and the generation of clinical interventional strategies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.