Fetal spina bifida associates with dysregulation in nutrient‐sensitive placental gene networks: Findings from a matched case–control study
Abstract To improve outcomes in fetuses with spina bifida (SB), better understanding is needed of the molecular drivers of SB and its comorbidities. Pregnant people carrying a fetus with isolated SB (cases; n = 12) or a fetus with no congenital anomalies (controls; n = 21) were recruited at Mount Si...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
|
| Series: | Clinical and Translational Science |
| Online Access: | https://doi.org/10.1111/cts.13710 |
| _version_ | 1827375126702718976 |
|---|---|
| author | Marina White Jayden Arif‐Pardy Tim Van Mieghem Kristin L. Connor |
| author_facet | Marina White Jayden Arif‐Pardy Tim Van Mieghem Kristin L. Connor |
| author_sort | Marina White |
| collection | DOAJ |
| description | Abstract To improve outcomes in fetuses with spina bifida (SB), better understanding is needed of the molecular drivers of SB and its comorbidities. Pregnant people carrying a fetus with isolated SB (cases; n = 12) or a fetus with no congenital anomalies (controls; n = 21) were recruited at Mount Sinai Hospital, Toronto, Ontario, Canada. Clinical data and placental samples were collected. Placental transcriptome was sequenced (Clariom D microarray) and a nutrient‐focused gene expression analysis pipeline was applied to determine whether fetal SB associates with placental dysfunction. Of the 391 differentially expressed genes (DEGs) in cases, 11% (n = 42) had at least one nutrient cofactor, including B vitamins (n = 7 genes), iron/heme (n = 6), and zinc (n = 11). Cases had dysregulation in genes not previously known to associate with SB, and in placental genes that have known links to SB but have not been previously identified in the placenta. Cases also had downregulated nutrient transport and upregulated branching angiogenesis and immune/inflammatory processes. Five nutrient‐dependent transcription regulators, collectively predicted to target 46% of DEGs in cases, were identified and were most commonly dependent on B vitamins (n = 3) and zinc (n = 2). Placental gene expression changes were most acute in cases with poor growth. Placentae from fetuses with SB have dysregulation in several gene networks, including those that are sensitive to multiple micronutrients beyond the well‐known folic acid. An improved understanding of placental phenotype in fetuses with SB may help identify novel mechanisms associated with comorbidities in fetuses with SB, and reveal new targets to improve fetal outcomes in this population. |
| first_indexed | 2024-03-08T11:46:16Z |
| format | Article |
| id | doaj.art-2f82cc98c79e49f7a7e28f80f4814bb0 |
| institution | Directory Open Access Journal |
| issn | 1752-8054 1752-8062 |
| language | English |
| last_indexed | 2024-03-08T11:46:16Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Science |
| spelling | doaj.art-2f82cc98c79e49f7a7e28f80f4814bb02024-01-24T18:33:50ZengWileyClinical and Translational Science1752-80541752-80622024-01-01171n/an/a10.1111/cts.13710Fetal spina bifida associates with dysregulation in nutrient‐sensitive placental gene networks: Findings from a matched case–control studyMarina White0Jayden Arif‐Pardy1Tim Van Mieghem2Kristin L. Connor3Health Sciences Carleton University Ottawa Ontario CanadaHealth Sciences Carleton University Ottawa Ontario CanadaDepartment of Obstetrics and Gynaecology Mount Sinai Hospital Toronto Ontario CanadaHealth Sciences Carleton University Ottawa Ontario CanadaAbstract To improve outcomes in fetuses with spina bifida (SB), better understanding is needed of the molecular drivers of SB and its comorbidities. Pregnant people carrying a fetus with isolated SB (cases; n = 12) or a fetus with no congenital anomalies (controls; n = 21) were recruited at Mount Sinai Hospital, Toronto, Ontario, Canada. Clinical data and placental samples were collected. Placental transcriptome was sequenced (Clariom D microarray) and a nutrient‐focused gene expression analysis pipeline was applied to determine whether fetal SB associates with placental dysfunction. Of the 391 differentially expressed genes (DEGs) in cases, 11% (n = 42) had at least one nutrient cofactor, including B vitamins (n = 7 genes), iron/heme (n = 6), and zinc (n = 11). Cases had dysregulation in genes not previously known to associate with SB, and in placental genes that have known links to SB but have not been previously identified in the placenta. Cases also had downregulated nutrient transport and upregulated branching angiogenesis and immune/inflammatory processes. Five nutrient‐dependent transcription regulators, collectively predicted to target 46% of DEGs in cases, were identified and were most commonly dependent on B vitamins (n = 3) and zinc (n = 2). Placental gene expression changes were most acute in cases with poor growth. Placentae from fetuses with SB have dysregulation in several gene networks, including those that are sensitive to multiple micronutrients beyond the well‐known folic acid. An improved understanding of placental phenotype in fetuses with SB may help identify novel mechanisms associated with comorbidities in fetuses with SB, and reveal new targets to improve fetal outcomes in this population.https://doi.org/10.1111/cts.13710 |
| spellingShingle | Marina White Jayden Arif‐Pardy Tim Van Mieghem Kristin L. Connor Fetal spina bifida associates with dysregulation in nutrient‐sensitive placental gene networks: Findings from a matched case–control study Clinical and Translational Science |
| title | Fetal spina bifida associates with dysregulation in nutrient‐sensitive placental gene networks: Findings from a matched case–control study |
| title_full | Fetal spina bifida associates with dysregulation in nutrient‐sensitive placental gene networks: Findings from a matched case–control study |
| title_fullStr | Fetal spina bifida associates with dysregulation in nutrient‐sensitive placental gene networks: Findings from a matched case–control study |
| title_full_unstemmed | Fetal spina bifida associates with dysregulation in nutrient‐sensitive placental gene networks: Findings from a matched case–control study |
| title_short | Fetal spina bifida associates with dysregulation in nutrient‐sensitive placental gene networks: Findings from a matched case–control study |
| title_sort | fetal spina bifida associates with dysregulation in nutrient sensitive placental gene networks findings from a matched case control study |
| url | https://doi.org/10.1111/cts.13710 |
| work_keys_str_mv | AT marinawhite fetalspinabifidaassociateswithdysregulationinnutrientsensitiveplacentalgenenetworksfindingsfromamatchedcasecontrolstudy AT jaydenarifpardy fetalspinabifidaassociateswithdysregulationinnutrientsensitiveplacentalgenenetworksfindingsfromamatchedcasecontrolstudy AT timvanmieghem fetalspinabifidaassociateswithdysregulationinnutrientsensitiveplacentalgenenetworksfindingsfromamatchedcasecontrolstudy AT kristinlconnor fetalspinabifidaassociateswithdysregulationinnutrientsensitiveplacentalgenenetworksfindingsfromamatchedcasecontrolstudy |