Fetal and maternal NLRP3 signaling is required for preterm labor and birth
Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. One of every 4 preterm neonates is born to a mother with intra-amniotic inflammation driven by invading bacteria. However, the molecular mechanisms underlying this hostile immune response remain unclear. Here, we used...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-08-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.158238 |
| _version_ | 1797634342783025152 |
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| author | Kenichiro Motomura Roberto Romero Jose Galaz Li Tao Valeria Garcia-Flores Yi Xu Bogdan Done Marcia Arenas-Hernandez Derek Miller Pedro Gutierrez-Contreras Marcelo Farias-Jofre Siddhesh Aras Lawrence I. Grossman Adi L. Tarca Nardhy Gomez-Lopez |
| author_facet | Kenichiro Motomura Roberto Romero Jose Galaz Li Tao Valeria Garcia-Flores Yi Xu Bogdan Done Marcia Arenas-Hernandez Derek Miller Pedro Gutierrez-Contreras Marcelo Farias-Jofre Siddhesh Aras Lawrence I. Grossman Adi L. Tarca Nardhy Gomez-Lopez |
| author_sort | Kenichiro Motomura |
| collection | DOAJ |
| description | Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. One of every 4 preterm neonates is born to a mother with intra-amniotic inflammation driven by invading bacteria. However, the molecular mechanisms underlying this hostile immune response remain unclear. Here, we used a translationally relevant model of preterm birth in Nlrp3-deficient and -sufficient pregnant mice to identify what we believe is a previously unknown dual role for the NLRP3 pathway in the fetal and maternal signaling required for the premature onset of the labor cascade leading to fetal injury and neonatal death. Specifically, the NLRP3 sensor molecule and/or inflammasome is essential for triggering intra-amniotic and decidual inflammation, fetal membrane activation, uterine contractility, and cervical dilation. NLRP3 also regulates the functional status of neutrophils and macrophages in the uterus and decidua, without altering their influx, as well as maternal systemic inflammation. Finally, both embryo transfer experimentation and heterozygous mating systems provided mechanistic evidence showing that NLRP3 signaling in both the fetus and the mother is required for the premature activation of the labor cascade. These data provide insights into the mechanisms of fetal-maternal dialog in the syndrome of preterm labor and indicate that targeting the NLRP3 pathway could prevent adverse perinatal outcomes. |
| first_indexed | 2024-03-11T12:07:18Z |
| format | Article |
| id | doaj.art-1adab97a357348e29510437ecaef7b91 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:07:18Z |
| publishDate | 2022-08-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-1adab97a357348e29510437ecaef7b912023-11-07T16:24:28ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-08-01716Fetal and maternal NLRP3 signaling is required for preterm labor and birthKenichiro MotomuraRoberto RomeroJose GalazLi TaoValeria Garcia-FloresYi XuBogdan DoneMarcia Arenas-HernandezDerek MillerPedro Gutierrez-ContrerasMarcelo Farias-JofreSiddhesh ArasLawrence I. GrossmanAdi L. TarcaNardhy Gomez-LopezPreterm birth is the leading cause of neonatal morbidity and mortality worldwide. One of every 4 preterm neonates is born to a mother with intra-amniotic inflammation driven by invading bacteria. However, the molecular mechanisms underlying this hostile immune response remain unclear. Here, we used a translationally relevant model of preterm birth in Nlrp3-deficient and -sufficient pregnant mice to identify what we believe is a previously unknown dual role for the NLRP3 pathway in the fetal and maternal signaling required for the premature onset of the labor cascade leading to fetal injury and neonatal death. Specifically, the NLRP3 sensor molecule and/or inflammasome is essential for triggering intra-amniotic and decidual inflammation, fetal membrane activation, uterine contractility, and cervical dilation. NLRP3 also regulates the functional status of neutrophils and macrophages in the uterus and decidua, without altering their influx, as well as maternal systemic inflammation. Finally, both embryo transfer experimentation and heterozygous mating systems provided mechanistic evidence showing that NLRP3 signaling in both the fetus and the mother is required for the premature activation of the labor cascade. These data provide insights into the mechanisms of fetal-maternal dialog in the syndrome of preterm labor and indicate that targeting the NLRP3 pathway could prevent adverse perinatal outcomes.https://doi.org/10.1172/jci.insight.158238ImmunologyReproductive biology |
| spellingShingle | Kenichiro Motomura Roberto Romero Jose Galaz Li Tao Valeria Garcia-Flores Yi Xu Bogdan Done Marcia Arenas-Hernandez Derek Miller Pedro Gutierrez-Contreras Marcelo Farias-Jofre Siddhesh Aras Lawrence I. Grossman Adi L. Tarca Nardhy Gomez-Lopez Fetal and maternal NLRP3 signaling is required for preterm labor and birth JCI Insight Immunology Reproductive biology |
| title | Fetal and maternal NLRP3 signaling is required for preterm labor and birth |
| title_full | Fetal and maternal NLRP3 signaling is required for preterm labor and birth |
| title_fullStr | Fetal and maternal NLRP3 signaling is required for preterm labor and birth |
| title_full_unstemmed | Fetal and maternal NLRP3 signaling is required for preterm labor and birth |
| title_short | Fetal and maternal NLRP3 signaling is required for preterm labor and birth |
| title_sort | fetal and maternal nlrp3 signaling is required for preterm labor and birth |
| topic | Immunology Reproductive biology |
| url | https://doi.org/10.1172/jci.insight.158238 |
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