Placental TNF-α Signaling in Illness-Induced Complications of Pregnancy
| Autor: | Theo D. Palmer, Andra L. Dingman, Pamela A. Carpentier |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Lipopolysaccharides
medicine.medical_specialty Complications of pregnancy Neurogenesis Placenta Biology Pathology and Forensic Medicine Proinflammatory cytokine Mice Fetus Neural Stem Cells Fetal membrane Pregnancy Internal medicine medicine Animals Cell Proliferation Tumor Necrosis Factor-alpha Immunity Brain Anatomical pathology Regular Article medicine.disease Embryo Mammalian Oxygen Pregnancy Complications Toll-Like Receptor 4 medicine.anatomical_structure Endocrinology Receptors Tumor Necrosis Factor Type I embryonic structures Embryo Loss Gestation Cytokines Female Signal Transduction |
| Popis: | Maternal infections are implicated in a variety of complications during pregnancy, including pregnancy loss, prematurity, and increased risk of neurodevelopmental disorders in the child. Here, we show in mice that even mild innate immune activation by low-dose lipopolysaccharide in early pregnancy causes hemorrhages in the placenta and increases the risk of pregnancy loss. Surviving fetuses exhibit hypoxia in the brain and impaired fetal neurogenesis. Maternal Toll-like receptor 4 signaling is a critical mediator of this process, and its activation is accompanied by elevated proinflammatory cytokines in the placenta. We evaluated the role of tumor necrosis factor-α (TNF-α) signaling and show that TNF receptor 1 (TNFR1) is necessary for the illness-induced placental pathology, accompanying fetal hypoxia, and neuroproliferative defects in the fetal brain. We also show that placental TNFR1 in the absence of maternal TNFR1 is sufficient for placental pathology to develop and that a clinically relevant TNF-α antagonist prevents placental pathology and fetal loss. Our observations suggest that the placenta is highly sensitive to proinflammatory signaling in early pregnancy and that TNF-α is an effective target for preventing illness-related placental defects and related risks to the fetus and fetal brain development. |
| Databáze: | OpenAIRE |
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