Integrative Review of Molecular, Metabolic, and Environmental Factors in Spina Bifida and Congenital Diaphragmatic Hernia: Insights into Mechanisms and Emerging Therapeutics
Spina Bifida (SB) and Congenital Diaphragmatic Hernia (CDH) are complex congenital anomalies that pose significant challenges in pediatric healthcare. This review synthesizes recent advancements in understanding the genetic, metabolic, and environmental factors contributing to these conditions, with...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/14/14/1059 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850078314502291456 |
|---|---|
| author | Angelika Buczyńska Iwona Sidorkiewicz Przemysław Kosiński Adam Jacek Krętowski Monika Zbucka-Krętowska |
| author_facet | Angelika Buczyńska Iwona Sidorkiewicz Przemysław Kosiński Adam Jacek Krętowski Monika Zbucka-Krętowska |
| author_sort | Angelika Buczyńska |
| collection | DOAJ |
| description | Spina Bifida (SB) and Congenital Diaphragmatic Hernia (CDH) are complex congenital anomalies that pose significant challenges in pediatric healthcare. This review synthesizes recent advancements in understanding the genetic, metabolic, and environmental factors contributing to these conditions, with the aim of integrating mechanistic insights into therapeutic innovations. In SB, key findings highlight the roles of <i>KCND3</i>, a critical regulator of spinal cord development, and <i>VANGL2</i>, essential for planar cell polarity and neural tube closure. MicroRNAs such as miR-765 and miR-142-3p are identified as key regulators of these genes, influencing neural development. Additionally, telomere shortening—a marker of cellular senescence—alongside disruptions in folate metabolism and maternal nutritional deficiencies, significantly increases the risk of SB. These findings underscore the crucial role of telomere integrity in maintaining neural tissue homeostasis during embryonic development. For CDH, genetic deletions, including those on chromosome 15q26, and chromosomal abnormalities have been shown to disrupt lung and vascular development, profoundly impacting neonatal outcomes. MicroRNAs miR-379-5p and miR-889-3p are implicated in targeting essential genes such as <i>IGF1</i> and <i>FGFR2</i>, which play pivotal roles in pulmonary function. Promising emerging therapies, including degradable tracheal plugs and fibroblast growth factor-based treatments, offer potential strategies for mitigating pulmonary hypoplasia and improving clinical outcomes. This review underscores the intricate interplay of genetic, metabolic, and environmental pathways in SB and CDH, identifying critical molecular targets for diagnostics and therapeutic intervention. By integrating findings from genetic profiling, in vitro models, and clinical studies, it aims to inform future research directions and optimize patient outcomes through collaborative, multidisciplinary approaches. |
| format | Article |
| id | doaj-art-1af05aab6f484ec09c04a3ea0134c352 |
| institution | DOAJ |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-1af05aab6f484ec09c04a3ea0134c3522025-08-20T02:45:34ZengMDPI AGCells2073-44092025-07-011414105910.3390/cells14141059Integrative Review of Molecular, Metabolic, and Environmental Factors in Spina Bifida and Congenital Diaphragmatic Hernia: Insights into Mechanisms and Emerging TherapeuticsAngelika Buczyńska0Iwona Sidorkiewicz1Przemysław Kosiński2Adam Jacek Krętowski3Monika Zbucka-Krętowska4Clinical Research Centre, Medical University of Białystok, ul. M. Skłodowskiej-Curie 24a, 15-276 Białystok, PolandClinical Research Support Centre, Medical University of Białystok, ul. M. Waszyngtona 17, 15-276 Białystok, PolandDepartment of Obstetrics, Perinatology and Gynecology, Medical University of Warsaw, 63A Zwirki i Wigury, 02-091 Warsaw, PolandClinical Research Centre, Medical University of Białystok, ul. M. Skłodowskiej-Curie 24a, 15-276 Białystok, PolandDepartment of Gynecological Endocrinology and Adolescent Gynecology, Medical University of Białystok, ul. M. Skłodowskiej-Curie 24a, 15-276 Białystok, PolandSpina Bifida (SB) and Congenital Diaphragmatic Hernia (CDH) are complex congenital anomalies that pose significant challenges in pediatric healthcare. This review synthesizes recent advancements in understanding the genetic, metabolic, and environmental factors contributing to these conditions, with the aim of integrating mechanistic insights into therapeutic innovations. In SB, key findings highlight the roles of <i>KCND3</i>, a critical regulator of spinal cord development, and <i>VANGL2</i>, essential for planar cell polarity and neural tube closure. MicroRNAs such as miR-765 and miR-142-3p are identified as key regulators of these genes, influencing neural development. Additionally, telomere shortening—a marker of cellular senescence—alongside disruptions in folate metabolism and maternal nutritional deficiencies, significantly increases the risk of SB. These findings underscore the crucial role of telomere integrity in maintaining neural tissue homeostasis during embryonic development. For CDH, genetic deletions, including those on chromosome 15q26, and chromosomal abnormalities have been shown to disrupt lung and vascular development, profoundly impacting neonatal outcomes. MicroRNAs miR-379-5p and miR-889-3p are implicated in targeting essential genes such as <i>IGF1</i> and <i>FGFR2</i>, which play pivotal roles in pulmonary function. Promising emerging therapies, including degradable tracheal plugs and fibroblast growth factor-based treatments, offer potential strategies for mitigating pulmonary hypoplasia and improving clinical outcomes. This review underscores the intricate interplay of genetic, metabolic, and environmental pathways in SB and CDH, identifying critical molecular targets for diagnostics and therapeutic intervention. By integrating findings from genetic profiling, in vitro models, and clinical studies, it aims to inform future research directions and optimize patient outcomes through collaborative, multidisciplinary approaches.https://www.mdpi.com/2073-4409/14/14/1059Spinal BifidaDiaphragmatic Herniagenetic patternmetabolic markers |
| spellingShingle | Angelika Buczyńska Iwona Sidorkiewicz Przemysław Kosiński Adam Jacek Krętowski Monika Zbucka-Krętowska Integrative Review of Molecular, Metabolic, and Environmental Factors in Spina Bifida and Congenital Diaphragmatic Hernia: Insights into Mechanisms and Emerging Therapeutics Cells Spinal Bifida Diaphragmatic Hernia genetic pattern metabolic markers |
| title | Integrative Review of Molecular, Metabolic, and Environmental Factors in Spina Bifida and Congenital Diaphragmatic Hernia: Insights into Mechanisms and Emerging Therapeutics |
| title_full | Integrative Review of Molecular, Metabolic, and Environmental Factors in Spina Bifida and Congenital Diaphragmatic Hernia: Insights into Mechanisms and Emerging Therapeutics |
| title_fullStr | Integrative Review of Molecular, Metabolic, and Environmental Factors in Spina Bifida and Congenital Diaphragmatic Hernia: Insights into Mechanisms and Emerging Therapeutics |
| title_full_unstemmed | Integrative Review of Molecular, Metabolic, and Environmental Factors in Spina Bifida and Congenital Diaphragmatic Hernia: Insights into Mechanisms and Emerging Therapeutics |
| title_short | Integrative Review of Molecular, Metabolic, and Environmental Factors in Spina Bifida and Congenital Diaphragmatic Hernia: Insights into Mechanisms and Emerging Therapeutics |
| title_sort | integrative review of molecular metabolic and environmental factors in spina bifida and congenital diaphragmatic hernia insights into mechanisms and emerging therapeutics |
| topic | Spinal Bifida Diaphragmatic Hernia genetic pattern metabolic markers |
| url | https://www.mdpi.com/2073-4409/14/14/1059 |
| work_keys_str_mv | AT angelikabuczynska integrativereviewofmolecularmetabolicandenvironmentalfactorsinspinabifidaandcongenitaldiaphragmaticherniainsightsintomechanismsandemergingtherapeutics AT iwonasidorkiewicz integrativereviewofmolecularmetabolicandenvironmentalfactorsinspinabifidaandcongenitaldiaphragmaticherniainsightsintomechanismsandemergingtherapeutics AT przemysławkosinski integrativereviewofmolecularmetabolicandenvironmentalfactorsinspinabifidaandcongenitaldiaphragmaticherniainsightsintomechanismsandemergingtherapeutics AT adamjacekkretowski integrativereviewofmolecularmetabolicandenvironmentalfactorsinspinabifidaandcongenitaldiaphragmaticherniainsightsintomechanismsandemergingtherapeutics AT monikazbuckakretowska integrativereviewofmolecularmetabolicandenvironmentalfactorsinspinabifidaandcongenitaldiaphragmaticherniainsightsintomechanismsandemergingtherapeutics |