Circulating syndecan-1 is reduced in pregnancies with poor fetal growth and its secretion regulated by matrix metalloproteinases and the mitochondria
Abstract Fetal growth restriction is a leading cause of stillbirth that often remains undetected during pregnancy. Identifying novel biomarkers may improve detection of pregnancies at risk. This study aimed to assess syndecan-1 as a biomarker for small for gestational age (SGA) or fetal growth restr...
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Nature Portfolio
2021
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oai:doaj.org-article:b9a4aa52db5d4a63b2d39175244dc8af2021-12-02T16:46:34ZCirculating syndecan-1 is reduced in pregnancies with poor fetal growth and its secretion regulated by matrix metalloproteinases and the mitochondria10.1038/s41598-021-96077-12045-2322https://doaj.org/article/b9a4aa52db5d4a63b2d39175244dc8af2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96077-1https://doaj.org/toc/2045-2322Abstract Fetal growth restriction is a leading cause of stillbirth that often remains undetected during pregnancy. Identifying novel biomarkers may improve detection of pregnancies at risk. This study aimed to assess syndecan-1 as a biomarker for small for gestational age (SGA) or fetal growth restricted (FGR) pregnancies and determine its molecular regulation. Circulating maternal syndecan-1 was measured in several cohorts; a large prospective cohort collected around 36 weeks’ gestation (n = 1206), a case control study from the Manchester Antenatal Vascular service (285 women sampled at 24–34 weeks’ gestation); two prospective cohorts collected on the day of delivery (36 + 3–41 + 3 weeks’ gestation, n = 562 and n = 405 respectively) and a cohort who delivered for preterm FGR (< 34 weeks). Circulating syndecan-1 was consistently reduced in women destined to deliver growth restricted infants and those delivering for preterm disease. Syndecan-1 secretion was reduced by hypoxia, and its loss impaired proliferation. Matrix metalloproteinases and mitochondrial electron transport chain inhibitors significantly reduced syndecan-1 secretion, an effect that was rescued by coadministration of succinate, a mitochondrial electron transport chain activator. In conclusion, circulating syndecan-1 is reduced among cases of term and preterm growth restriction and has potential for inclusion in multi-marker algorithms to improve detection of poorly grown fetuses.Damanpreet GarchaSusan P. WalkerTeresa M. MacDonaldJon HyettJessica JellinsJenny MyersSebastian E. IllanesJhy K. NienManuel SchepelerEmerson KeenanCarole-Anne WhighamPing CannonElizabeth MurrayTuong-Vi NguyenManju KandelJoshua MasciCiara MurphyTess CruickshankNatasha PritchardNatalie J. HannanFiona BrownfootAlexandra Roddy MitchellAnna MiddletonGabrielle PellGeorgia P. WongStephen TongTu’uhevaha J. Kaitu’u-LinoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) |
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Medicine R Science Q |
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Medicine R Science Q Damanpreet Garcha Susan P. Walker Teresa M. MacDonald Jon Hyett Jessica Jellins Jenny Myers Sebastian E. Illanes Jhy K. Nien Manuel Schepeler Emerson Keenan Carole-Anne Whigham Ping Cannon Elizabeth Murray Tuong-Vi Nguyen Manju Kandel Joshua Masci Ciara Murphy Tess Cruickshank Natasha Pritchard Natalie J. Hannan Fiona Brownfoot Alexandra Roddy Mitchell Anna Middleton Gabrielle Pell Georgia P. Wong Stephen Tong Tu’uhevaha J. Kaitu’u-Lino Circulating syndecan-1 is reduced in pregnancies with poor fetal growth and its secretion regulated by matrix metalloproteinases and the mitochondria |
| description |
Abstract Fetal growth restriction is a leading cause of stillbirth that often remains undetected during pregnancy. Identifying novel biomarkers may improve detection of pregnancies at risk. This study aimed to assess syndecan-1 as a biomarker for small for gestational age (SGA) or fetal growth restricted (FGR) pregnancies and determine its molecular regulation. Circulating maternal syndecan-1 was measured in several cohorts; a large prospective cohort collected around 36 weeks’ gestation (n = 1206), a case control study from the Manchester Antenatal Vascular service (285 women sampled at 24–34 weeks’ gestation); two prospective cohorts collected on the day of delivery (36 + 3–41 + 3 weeks’ gestation, n = 562 and n = 405 respectively) and a cohort who delivered for preterm FGR (< 34 weeks). Circulating syndecan-1 was consistently reduced in women destined to deliver growth restricted infants and those delivering for preterm disease. Syndecan-1 secretion was reduced by hypoxia, and its loss impaired proliferation. Matrix metalloproteinases and mitochondrial electron transport chain inhibitors significantly reduced syndecan-1 secretion, an effect that was rescued by coadministration of succinate, a mitochondrial electron transport chain activator. In conclusion, circulating syndecan-1 is reduced among cases of term and preterm growth restriction and has potential for inclusion in multi-marker algorithms to improve detection of poorly grown fetuses. |
| format |
article |
| author |
Damanpreet Garcha Susan P. Walker Teresa M. MacDonald Jon Hyett Jessica Jellins Jenny Myers Sebastian E. Illanes Jhy K. Nien Manuel Schepeler Emerson Keenan Carole-Anne Whigham Ping Cannon Elizabeth Murray Tuong-Vi Nguyen Manju Kandel Joshua Masci Ciara Murphy Tess Cruickshank Natasha Pritchard Natalie J. Hannan Fiona Brownfoot Alexandra Roddy Mitchell Anna Middleton Gabrielle Pell Georgia P. Wong Stephen Tong Tu’uhevaha J. Kaitu’u-Lino |
| author_facet |
Damanpreet Garcha Susan P. Walker Teresa M. MacDonald Jon Hyett Jessica Jellins Jenny Myers Sebastian E. Illanes Jhy K. Nien Manuel Schepeler Emerson Keenan Carole-Anne Whigham Ping Cannon Elizabeth Murray Tuong-Vi Nguyen Manju Kandel Joshua Masci Ciara Murphy Tess Cruickshank Natasha Pritchard Natalie J. Hannan Fiona Brownfoot Alexandra Roddy Mitchell Anna Middleton Gabrielle Pell Georgia P. Wong Stephen Tong Tu’uhevaha J. Kaitu’u-Lino |
| author_sort |
Damanpreet Garcha |
| title |
Circulating syndecan-1 is reduced in pregnancies with poor fetal growth and its secretion regulated by matrix metalloproteinases and the mitochondria |
| title_short |
Circulating syndecan-1 is reduced in pregnancies with poor fetal growth and its secretion regulated by matrix metalloproteinases and the mitochondria |
| title_full |
Circulating syndecan-1 is reduced in pregnancies with poor fetal growth and its secretion regulated by matrix metalloproteinases and the mitochondria |
| title_fullStr |
Circulating syndecan-1 is reduced in pregnancies with poor fetal growth and its secretion regulated by matrix metalloproteinases and the mitochondria |
| title_full_unstemmed |
Circulating syndecan-1 is reduced in pregnancies with poor fetal growth and its secretion regulated by matrix metalloproteinases and the mitochondria |
| title_sort |
circulating syndecan-1 is reduced in pregnancies with poor fetal growth and its secretion regulated by matrix metalloproteinases and the mitochondria |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/b9a4aa52db5d4a63b2d39175244dc8af |
| work_keys_str_mv |
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