Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth
Abstract Background Preterm birth (PTB), defined as infant delivery before 37 weeks of completed gestation, results from the interaction of both genetic and environmental components and constitutes a complex multifactorial syndrome. Transcriptome analysis of PTB has proven challenging because of the...
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| Format: | Article |
| Language: | English |
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BMC
2019-04-01
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| Series: | BMC Medical Genomics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12920-019-0498-3 |
| _version_ | 1818458197428535296 |
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| author | Silvana Pereyra Claudio Sosa Bernardo Bertoni Rossana Sapiro |
| author_facet | Silvana Pereyra Claudio Sosa Bernardo Bertoni Rossana Sapiro |
| author_sort | Silvana Pereyra |
| collection | DOAJ |
| description | Abstract Background Preterm birth (PTB), defined as infant delivery before 37 weeks of completed gestation, results from the interaction of both genetic and environmental components and constitutes a complex multifactorial syndrome. Transcriptome analysis of PTB has proven challenging because of the multiple causes of PTB and the numerous maternal and fetal gestational tissues that must interact to facilitate parturition. The transcriptome of the chorioamnion membranes at the site of rupture in PTB and term fetuses may reflect the molecular pathways of preterm labor. Methods In this work, chorioamnion membranes from severe preterm and term fetuses were analyzed using RNA sequencing. Functional annotations and pathway analysis of differentially expressed genes were performed with the GAGE and GOSeq packages. A subset of differentially expressed genes in PTB was validated in a larger cohort using qRT-PCR and by comparing our results with genes and pathways previously reported in the literature. Results A total of 270 genes were differentially expressed (DE): 252 were upregulated and 18 were down-regulated in severe preterm births relative to term births. Inflammatory and immunological pathways were upregulated in PTB. Both types of pathways were previously suggested to lead to PTB. Pathways that were not previously reported in PTB, such as the hemopoietic pathway, appeared upregulated in preterm membranes. A group of 18 downregulated genes discriminated between term and severe preterm cases. These genes potentially characterize a severe preterm transcriptome pattern and therefore are candidate genes for understanding the syndrome. Some of the downregulated genes are involved in the nervous system, morphogenesis (WNT1, DLX5, PAPPA2) and ion channel complexes (KCNJ16, KCNB1), making them good candidates as biomarkers of PTB. Conclusions The identification of this DE gene pattern will help with the development of a multi-gene disease classifier. These markers were generated in an admixed South American population in which PTB has a high incidence. Since the genetic background may differentially impact different populations, it is necessary to include populations such as those from South America and Africa, which are usually excluded from high-throughput approaches. These classifiers should be compared to those in other populations to obtain a global landscape of PTB. |
| first_indexed | 2024-12-14T22:54:38Z |
| format | Article |
| id | doaj.art-fcc45824f19847f19e2429f220e0fecd |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-12-14T22:54:38Z |
| publishDate | 2019-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-fcc45824f19847f19e2429f220e0fecd2022-12-21T22:44:38ZengBMCBMC Medical Genomics1755-87942019-04-0112111410.1186/s12920-019-0498-3Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birthSilvana Pereyra0Claudio Sosa1Bernardo Bertoni2Rossana Sapiro3Departamento de Genética, Facultad de Medicina, Universidad de la RepúblicaClínica Ginecotologica “C”, Centro Hospitalario Pereira Rossell, Facultad de Medicina, Universidad de la RepúblicaDepartamento de Genética, Facultad de Medicina, Universidad de la RepúblicaDepartamento de Histología y Embriología, Facultad de Medicina, Universidad de la RepúblicaAbstract Background Preterm birth (PTB), defined as infant delivery before 37 weeks of completed gestation, results from the interaction of both genetic and environmental components and constitutes a complex multifactorial syndrome. Transcriptome analysis of PTB has proven challenging because of the multiple causes of PTB and the numerous maternal and fetal gestational tissues that must interact to facilitate parturition. The transcriptome of the chorioamnion membranes at the site of rupture in PTB and term fetuses may reflect the molecular pathways of preterm labor. Methods In this work, chorioamnion membranes from severe preterm and term fetuses were analyzed using RNA sequencing. Functional annotations and pathway analysis of differentially expressed genes were performed with the GAGE and GOSeq packages. A subset of differentially expressed genes in PTB was validated in a larger cohort using qRT-PCR and by comparing our results with genes and pathways previously reported in the literature. Results A total of 270 genes were differentially expressed (DE): 252 were upregulated and 18 were down-regulated in severe preterm births relative to term births. Inflammatory and immunological pathways were upregulated in PTB. Both types of pathways were previously suggested to lead to PTB. Pathways that were not previously reported in PTB, such as the hemopoietic pathway, appeared upregulated in preterm membranes. A group of 18 downregulated genes discriminated between term and severe preterm cases. These genes potentially characterize a severe preterm transcriptome pattern and therefore are candidate genes for understanding the syndrome. Some of the downregulated genes are involved in the nervous system, morphogenesis (WNT1, DLX5, PAPPA2) and ion channel complexes (KCNJ16, KCNB1), making them good candidates as biomarkers of PTB. Conclusions The identification of this DE gene pattern will help with the development of a multi-gene disease classifier. These markers were generated in an admixed South American population in which PTB has a high incidence. Since the genetic background may differentially impact different populations, it is necessary to include populations such as those from South America and Africa, which are usually excluded from high-throughput approaches. These classifiers should be compared to those in other populations to obtain a global landscape of PTB.http://link.springer.com/article/10.1186/s12920-019-0498-3RNA-SeqPreterm birthGestational ageBiomarkers |
| spellingShingle | Silvana Pereyra Claudio Sosa Bernardo Bertoni Rossana Sapiro Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth BMC Medical Genomics RNA-Seq Preterm birth Gestational age Biomarkers |
| title | Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth |
| title_full | Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth |
| title_fullStr | Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth |
| title_full_unstemmed | Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth |
| title_short | Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth |
| title_sort | transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth |
| topic | RNA-Seq Preterm birth Gestational age Biomarkers |
| url | http://link.springer.com/article/10.1186/s12920-019-0498-3 |
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