Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta
Placental insufficiency is implicated in spontaneous preterm birth (SPTB) associated with intrauterine inflammation. We hypothesized that intrauterine inflammation leads to deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy ultimately resulting...
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2020.592689/full |
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| author | Yu-Chin Lien Yu-Chin Lien Zhe Zhang Guillermo Barila Amy Green-Brown Michal A. Elovitz Rebecca A. Simmons Rebecca A. Simmons |
| author_facet | Yu-Chin Lien Yu-Chin Lien Zhe Zhang Guillermo Barila Amy Green-Brown Michal A. Elovitz Rebecca A. Simmons Rebecca A. Simmons |
| author_sort | Yu-Chin Lien |
| collection | DOAJ |
| description | Placental insufficiency is implicated in spontaneous preterm birth (SPTB) associated with intrauterine inflammation. We hypothesized that intrauterine inflammation leads to deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy ultimately resulting in SPTB. Using a mouse model of intrauterine inflammation that leads to preterm delivery, we performed RNA-seq and metabolomics studies to assess how intrauterine inflammation alters gene expression and/or modulates metabolite production and abundance in the placenta. 1871 differentially expressed genes were identified in LPS-exposed placenta. Among them, 1,149 and 722 transcripts were increased and decreased, respectively. Ingenuity pathway analysis showed alterations in genes and canonical pathways critical for regulating oxidative stress, mitochondrial function, metabolisms of glucose and lipids, and vascular reactivity in LPS-exposed placenta. Many upstream regulators and master regulators important for nutrient-sensing and mitochondrial function were also altered in inflammation exposed placentae, including STAT1, HIF1α, mTOR, AMPK, and PPARα. Comprehensive quantification of metabolites demonstrated significant alterations in the glucose utilization, metabolisms of branched-chain amino acids, lipids, purine and pyrimidine, as well as carbon flow in TCA cycle in LPS-exposed placenta compared to control placenta. The transcriptome and metabolome were also integrated to assess the interactions of altered genes and metabolites. Collectively, significant and biologically relevant alterations in the placenta transcriptome and metabolome were identified in placentae exposed to intrauterine inflammation. Altered mitochondrial function and energy metabolism may underline the mechanisms of inflammation-induced placental dysfunction. |
| first_indexed | 2024-12-13T15:55:57Z |
| format | Article |
| id | doaj.art-972fa3705d1d461b8b5f99fd54f7ef90 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-13T15:55:57Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-972fa3705d1d461b8b5f99fd54f7ef902022-12-21T23:39:20ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-11-011110.3389/fphys.2020.592689592689Intrauterine Inflammation Alters the Transcriptome and Metabolome in PlacentaYu-Chin Lien0Yu-Chin Lien1Zhe Zhang2Guillermo Barila3Amy Green-Brown4Michal A. Elovitz5Rebecca A. Simmons6Rebecca A. Simmons7Department of Obstetrics and Gynecology, Maternal and Child Health Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesCenter for Biomedical Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Obstetrics and Gynecology, Maternal and Child Health Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Obstetrics and Gynecology, Maternal and Child Health Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Obstetrics and Gynecology, Maternal and Child Health Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Obstetrics and Gynecology, Maternal and Child Health Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesPlacental insufficiency is implicated in spontaneous preterm birth (SPTB) associated with intrauterine inflammation. We hypothesized that intrauterine inflammation leads to deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy ultimately resulting in SPTB. Using a mouse model of intrauterine inflammation that leads to preterm delivery, we performed RNA-seq and metabolomics studies to assess how intrauterine inflammation alters gene expression and/or modulates metabolite production and abundance in the placenta. 1871 differentially expressed genes were identified in LPS-exposed placenta. Among them, 1,149 and 722 transcripts were increased and decreased, respectively. Ingenuity pathway analysis showed alterations in genes and canonical pathways critical for regulating oxidative stress, mitochondrial function, metabolisms of glucose and lipids, and vascular reactivity in LPS-exposed placenta. Many upstream regulators and master regulators important for nutrient-sensing and mitochondrial function were also altered in inflammation exposed placentae, including STAT1, HIF1α, mTOR, AMPK, and PPARα. Comprehensive quantification of metabolites demonstrated significant alterations in the glucose utilization, metabolisms of branched-chain amino acids, lipids, purine and pyrimidine, as well as carbon flow in TCA cycle in LPS-exposed placenta compared to control placenta. The transcriptome and metabolome were also integrated to assess the interactions of altered genes and metabolites. Collectively, significant and biologically relevant alterations in the placenta transcriptome and metabolome were identified in placentae exposed to intrauterine inflammation. Altered mitochondrial function and energy metabolism may underline the mechanisms of inflammation-induced placental dysfunction.https://www.frontiersin.org/articles/10.3389/fphys.2020.592689/fullplacentatranscriptomemetabolomeinflammationspontaneous preterm birthbioenergetic metabolism |
| spellingShingle | Yu-Chin Lien Yu-Chin Lien Zhe Zhang Guillermo Barila Amy Green-Brown Michal A. Elovitz Rebecca A. Simmons Rebecca A. Simmons Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta Frontiers in Physiology placenta transcriptome metabolome inflammation spontaneous preterm birth bioenergetic metabolism |
| title | Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta |
| title_full | Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta |
| title_fullStr | Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta |
| title_full_unstemmed | Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta |
| title_short | Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta |
| title_sort | intrauterine inflammation alters the transcriptome and metabolome in placenta |
| topic | placenta transcriptome metabolome inflammation spontaneous preterm birth bioenergetic metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2020.592689/full |
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