The Impact of Mouse Preterm Birth Induction by RU-486 on Microglial Activation and Subsequent Hypomyelination
Preterm birth (PTB) represents 15 million births every year worldwide and is frequently associated with maternal/fetal infections and inflammation, inducing neuroinflammation. This neuroinflammation is mediated by microglial cells, which are brain-resident macrophages that release cytotoxic molecule...
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/9/4867 |
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| author | Cécile Morin David Guenoun Irvin Sautet Valérie Faivre Zsolt Csaba Leslie Schwendimann Pierrette Young-Ten Juliette Van Steenwinckel Pierre Gressens Cindy Bokobza |
| author_facet | Cécile Morin David Guenoun Irvin Sautet Valérie Faivre Zsolt Csaba Leslie Schwendimann Pierrette Young-Ten Juliette Van Steenwinckel Pierre Gressens Cindy Bokobza |
| author_sort | Cécile Morin |
| collection | DOAJ |
| description | Preterm birth (PTB) represents 15 million births every year worldwide and is frequently associated with maternal/fetal infections and inflammation, inducing neuroinflammation. This neuroinflammation is mediated by microglial cells, which are brain-resident macrophages that release cytotoxic molecules that block oligodendrocyte differentiation, leading to hypomyelination. Some preterm survivors can face lifetime motor and/or cognitive disabilities linked to periventricular white matter injuries (PWMIs). There is currently no recommendation concerning the mode of delivery in the case of PTB and its impact on brain development. Many animal models of induced-PTB based on LPS injections exist, but with a low survival rate. There is a lack of information regarding clinically used pharmacological substances to induce PTB and their consequences on brain development. Mifepristone (RU-486) is a drug used clinically to induce preterm labor. This study aims to elaborate and characterize a new model of induced-PTB and PWMIs by the gestational injection of RU-486 and the perinatal injection of pups with IL-1beta. A RU-486 single subcutaneous (s.c.) injection at embryonic day (E)18.5 induced PTB at E19.5 in pregnant OF1 mice. All pups were born alive and were adopted directly after birth. IL-1beta was injected intraperitoneally from postnatal day (P)1 to P5. Animals exposed to both RU-486 and IL-1beta demonstrated microglial reactivity and subsequent PWMIs. In conclusion, the s.c. administration of RU-486 induced labor within 24 h with a high survival rate for pups. In the context of perinatal inflammation, RU-486 labor induction significantly decreases microglial reactivity in vivo but did not prevent subsequent PWMIs. |
| first_indexed | 2024-03-10T04:05:37Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:05:37Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-aeaea988e1b94f61a8afad11c89713492023-11-23T08:23:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239486710.3390/ijms23094867The Impact of Mouse Preterm Birth Induction by RU-486 on Microglial Activation and Subsequent HypomyelinationCécile Morin0David Guenoun1Irvin Sautet2Valérie Faivre3Zsolt Csaba4Leslie Schwendimann5Pierrette Young-Ten6Juliette Van Steenwinckel7Pierre Gressens8Cindy Bokobza9NeuroDiderot, Inserm UMR-1141, Hôpital Robert Debré, Université de Paris, 75019 Paris, FranceNeuroDiderot, Inserm UMR-1141, Hôpital Robert Debré, Université de Paris, 75019 Paris, FranceNeuroDiderot, Inserm UMR-1141, Hôpital Robert Debré, Université de Paris, 75019 Paris, FranceNeuroDiderot, Inserm UMR-1141, Hôpital Robert Debré, Université de Paris, 75019 Paris, FranceNeuroDiderot, Inserm UMR-1141, Hôpital Robert Debré, Université de Paris, 75019 Paris, FranceNeuroDiderot, Inserm UMR-1141, Hôpital Robert Debré, Université de Paris, 75019 Paris, FranceNeuroDiderot, Inserm UMR-1141, Hôpital Robert Debré, Université de Paris, 75019 Paris, FranceNeuroDiderot, Inserm UMR-1141, Hôpital Robert Debré, Université de Paris, 75019 Paris, FranceNeuroDiderot, Inserm UMR-1141, Hôpital Robert Debré, Université de Paris, 75019 Paris, FranceNeuroDiderot, Inserm UMR-1141, Hôpital Robert Debré, Université de Paris, 75019 Paris, FrancePreterm birth (PTB) represents 15 million births every year worldwide and is frequently associated with maternal/fetal infections and inflammation, inducing neuroinflammation. This neuroinflammation is mediated by microglial cells, which are brain-resident macrophages that release cytotoxic molecules that block oligodendrocyte differentiation, leading to hypomyelination. Some preterm survivors can face lifetime motor and/or cognitive disabilities linked to periventricular white matter injuries (PWMIs). There is currently no recommendation concerning the mode of delivery in the case of PTB and its impact on brain development. Many animal models of induced-PTB based on LPS injections exist, but with a low survival rate. There is a lack of information regarding clinically used pharmacological substances to induce PTB and their consequences on brain development. Mifepristone (RU-486) is a drug used clinically to induce preterm labor. This study aims to elaborate and characterize a new model of induced-PTB and PWMIs by the gestational injection of RU-486 and the perinatal injection of pups with IL-1beta. A RU-486 single subcutaneous (s.c.) injection at embryonic day (E)18.5 induced PTB at E19.5 in pregnant OF1 mice. All pups were born alive and were adopted directly after birth. IL-1beta was injected intraperitoneally from postnatal day (P)1 to P5. Animals exposed to both RU-486 and IL-1beta demonstrated microglial reactivity and subsequent PWMIs. In conclusion, the s.c. administration of RU-486 induced labor within 24 h with a high survival rate for pups. In the context of perinatal inflammation, RU-486 labor induction significantly decreases microglial reactivity in vivo but did not prevent subsequent PWMIs.https://www.mdpi.com/1422-0067/23/9/4867preterm birthinduced labormifepristoneRU-486microgliaoligodendrocyte maturation |
| spellingShingle | Cécile Morin David Guenoun Irvin Sautet Valérie Faivre Zsolt Csaba Leslie Schwendimann Pierrette Young-Ten Juliette Van Steenwinckel Pierre Gressens Cindy Bokobza The Impact of Mouse Preterm Birth Induction by RU-486 on Microglial Activation and Subsequent Hypomyelination International Journal of Molecular Sciences preterm birth induced labor mifepristone RU-486 microglia oligodendrocyte maturation |
| title | The Impact of Mouse Preterm Birth Induction by RU-486 on Microglial Activation and Subsequent Hypomyelination |
| title_full | The Impact of Mouse Preterm Birth Induction by RU-486 on Microglial Activation and Subsequent Hypomyelination |
| title_fullStr | The Impact of Mouse Preterm Birth Induction by RU-486 on Microglial Activation and Subsequent Hypomyelination |
| title_full_unstemmed | The Impact of Mouse Preterm Birth Induction by RU-486 on Microglial Activation and Subsequent Hypomyelination |
| title_short | The Impact of Mouse Preterm Birth Induction by RU-486 on Microglial Activation and Subsequent Hypomyelination |
| title_sort | impact of mouse preterm birth induction by ru 486 on microglial activation and subsequent hypomyelination |
| topic | preterm birth induced labor mifepristone RU-486 microglia oligodendrocyte maturation |
| url | https://www.mdpi.com/1422-0067/23/9/4867 |
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