Maternal Progesterone Treatment Reduces Maternal Inflammation-Induced Fetal Brain Injury in a Mouse Model of Preterm Birth
Maternal natural vaginal progesterone (nVP) administration has been shown to reduce the risk of preterm birth (PTB). The largest randomized trial of nVP for PTB (OPPTIMUM) noted a sonographic reduction in neonatal brain injury following nVP treatment. We investigated the neuroinflammatory protective effect of maternal nVP in a mouse model for maternal inflammation. Pregnant mice (n = 24) were randomized to nVP (1 mg/day) or vehicle from days 13-16 of gestation. At days 15 and 16, lipopolysaccharide (30 μg) or saline were administered. Mice were sacrificed 4 h following the last injection. Fetal brains and placentas were collected. Levels of NF-κB, nNOS, IL-6, and TNFα were determined by Western blot. Maternal lipopolysaccharide significantly increased fetal brain levels of IL-6 (0.33 ± 0.02 vs. 0.11 ± 0.01 u), TNFα (0.3 ± 0.02 vs. 0.10 ± 0.01 u), NF-κB (0.32 ± 0.01 vs. 0.17 ± 0.01 u), and nNOS (0.24 ± 0.04 vs. 0.08 ± 0.01 u), and reduced the total glutathione levels (0.014 ± 0.001 vs. 0.026 ± 0.001 pmol/μl; p < 0.01) compared with control. Maternal nVP significantly reduced fetal brain levels of IL-6 (0.14 ± 0.01 vs. 0.33 ± 0.02 u), TNFα (0.2 ± 0.06 vs. 0.3 ± 0.02 u), NF-κB (0.16 ± 0.01 vs 0.32 ± 0.01 u), and nNOS (0.14 ± 0.01 vs 0.24 ± 0.04 u), and prevented the reduction of fetal brain total glutathione levels (0.022 ± 0.001 vs. 0.014 ± 0.001 pmol/μl; p < 0.01) to levels similar to controls. A similar pattern was demonstrated in the placenta. Maternal nVP for PTB may protect the fetal brain from inflammation-induced brain injury by inhibiting specific inflammatory and oxidative pathways in both brain and placenta.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Reproductive sciences (Thousand Oaks, Calif.) - 28(2021), 1 vom: 30. Jan., Seite 166-176 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ginsberg, Yuval [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.11.2021 Date Revised 26.02.2024 published: Print-Electronic ErratumIn: Reprod Sci. 2020 Sep 23;:. - PMID 32968934 Citation Status MEDLINE |
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| doi: |
10.1007/s43032-020-00272-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM314066500 |
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| 520 | |a Maternal natural vaginal progesterone (nVP) administration has been shown to reduce the risk of preterm birth (PTB). The largest randomized trial of nVP for PTB (OPPTIMUM) noted a sonographic reduction in neonatal brain injury following nVP treatment. We investigated the neuroinflammatory protective effect of maternal nVP in a mouse model for maternal inflammation. Pregnant mice (n = 24) were randomized to nVP (1 mg/day) or vehicle from days 13-16 of gestation. At days 15 and 16, lipopolysaccharide (30 μg) or saline were administered. Mice were sacrificed 4 h following the last injection. Fetal brains and placentas were collected. Levels of NF-κB, nNOS, IL-6, and TNFα were determined by Western blot. Maternal lipopolysaccharide significantly increased fetal brain levels of IL-6 (0.33 ± 0.02 vs. 0.11 ± 0.01 u), TNFα (0.3 ± 0.02 vs. 0.10 ± 0.01 u), NF-κB (0.32 ± 0.01 vs. 0.17 ± 0.01 u), and nNOS (0.24 ± 0.04 vs. 0.08 ± 0.01 u), and reduced the total glutathione levels (0.014 ± 0.001 vs. 0.026 ± 0.001 pmol/μl; p < 0.01) compared with control. Maternal nVP significantly reduced fetal brain levels of IL-6 (0.14 ± 0.01 vs. 0.33 ± 0.02 u), TNFα (0.2 ± 0.06 vs. 0.3 ± 0.02 u), NF-κB (0.16 ± 0.01 vs 0.32 ± 0.01 u), and nNOS (0.14 ± 0.01 vs 0.24 ± 0.04 u), and prevented the reduction of fetal brain total glutathione levels (0.022 ± 0.001 vs. 0.014 ± 0.001 pmol/μl; p < 0.01) to levels similar to controls. A similar pattern was demonstrated in the placenta. Maternal nVP for PTB may protect the fetal brain from inflammation-induced brain injury by inhibiting specific inflammatory and oxidative pathways in both brain and placenta | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Fetal brain injury | |
| 650 | 4 | |a Maternal inflammation | |
| 650 | 4 | |a Oxidative stress | |
| 650 | 4 | |a Preterm birth | |
| 650 | 4 | |a Progesterone | |
| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 650 | 7 | |a Antioxidants |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Inflammation Mediators |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a Neuroprotective Agents |2 NLM | |
| 650 | 7 | |a lipopolysaccharide, Escherichia coli O111 B4 |2 NLM | |
| 650 | 7 | |a Progesterone |2 NLM | |
| 650 | 7 | |a 4G7DS2Q64Y |2 NLM | |
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| 700 | 1 | |a Khatib, Nizar |e verfasserin |4 aut | |
| 700 | 1 | |a Fainaru, Ofer |e verfasserin |4 aut | |
| 700 | 1 | |a Weiner, Zeev |e verfasserin |4 aut | |
| 700 | 1 | |a Beloosesky, Ron |e verfasserin |4 aut | |
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