Administration of melatonin for prevention of preterm birth and fetal brain injury associated with premature birth in a mouse model
| Autor: | Ji Yeon Lee, Haengseok Song, Mira Park, Michael W. McLane, Irina Burd, Jun Lei, Oyunbileg Dash, Jong Yun Hwang, Na E. Shin |
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| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Offspring Immunology Physiology Proinflammatory cytokine Immunomodulation Melatonin Mice 03 medical and health sciences 0302 clinical medicine Pregnancy Placenta medicine Animals Humans Immunology and Allergy Neuroinflammation Inflammation Mice Inbred ICR Fetus 030219 obstetrics & reproductive medicine business.industry Hemodynamics Pregnancy Outcome Obstetrics and Gynecology medicine.disease Disease Models Animal Fetal Diseases 030104 developmental biology medicine.anatomical_structure Reproductive Medicine Maternal Exposure Premature birth Brain Injuries Premature Birth Female business Injections Intraperitoneal medicine.drug |
| Zdroj: | American Journal of Reproductive Immunology. 82 |
| ISSN: | 1600-0897 1046-7408 |
| DOI: | 10.1111/aji.13151 |
| Popis: | Problem Maternal inflammation leads to preterm birth and perinatal brain injury. Melatonin, through its anti-inflammatory effects, has been shown to be protective against inflammation-induced perinatal adverse effects. However, the immunomodulatory effects of melatonin on preterm birth and prematurity-related morbidity remain unknown. We wanted to investigate the effects of maternally administered melatonin on preterm birth and perinatal brain injury in a mouse model of maternal inflammation. Method of study A model of maternal inflammation employing lipopolysaccharide (LPS) was used to mimic the most common clinical scenario of preterm birth, that of maternal inflammation. Mice were randomly divided into the following groups: control, LPS, and LPS with melatonin pre-treatment. Doppler ultrasonography was used to obtain fetal and maternal hemodynamic measurements in utero. Placenta and fetal brains were harvested and analyzed for proinflammatory markers and signs of perinatal brain injury, respectively. Surviving offspring were assessed for neuromotor outcomes. Results Melatonin pre-treatment lowered the level of proinflammatory cytokines in the uterus and the placenta, significantly improved LPS-induced acute fetal neuroinflammation and perinatal brain injury, as well as significantly upregulated the SIRT1/Nrf2 signaling pathway to reduce LPS-induced inflammation. Melatonin also prevented adverse neuromotor outcomes in offspring exposed to maternal inflammation. Conclusion Maternally administered melatonin modulated immune responses to maternal inflammation and decreased preterm birth and perinatal brain injury. These results suggest that melatonin, a safe treatment during pregnancy, may be used as an experimental therapeutic in clinical trials. |
| Databáze: | OpenAIRE |
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