Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation
| Autor: | Chressen C. Remus, Gabriele Sass, Kurt Hecher, Hoang Ho, Francesco J. DeMayo, Andrea Kristina Horst, Petra C. Arck, Robert G. Berger, Torsten Plösch, Greta O’Rourke, C.A. Jago, Khalil Karimi, R Barikbin, Mirka Katharina Kowal, John P. Lydon, Kathrin Modest, V. J. Parker, Maria Emilia Solano |
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| Přispěvatelé: | Reproductive Origins of Adult Health and Disease (ROAHD), Center for Liver, Digestive and Metabolic Diseases (CLDM) |
| Rok vydání: | 2015 |
| Předmět: |
Male
HMOX1 Placenta Drug Evaluation Preclinical CD8-Positive T-Lymphocytes Fetal Development Mice Pregnancy Cytotoxic T cell OXIDATIVE STRESS Promoter Regions Genetic GESTATIONAL-AGE Progesterone HO-1 EXPRESSION Mice Inbred BALB C Fetal Growth Retardation General Medicine medicine.anatomical_structure Mice Inbred DBA STRESS-TRIGGERED ABORTION Female Research Article medicine.medical_specialty Placental insufficiency Biology Fetus Internal medicine Progesterone receptor medicine Animals Placental Circulation RNA Messenger CARBON-MONOXIDE MOUSE PLACENTA TERM HUMAN PLACENTA HEME OXYGENASE EXPRESSION Membrane Proteins DNA Methylation Placental Insufficiency medicine.disease BIRTH-WEIGHT Mice Inbred C57BL Pregnancy Complications Heme oxygenase Disease Models Animal Endocrinology RISK-FACTORS Noise Heme Oxygenase-1 Stress Psychological CD8 |
| Zdroj: | CLIN Journal, 125(4), 1726-1738. AMER SOC CLINICAL INVESTIGATION INC |
| ISSN: | 0021-9738 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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