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Published on: January 26, 2024
Circulating RNA coding genes regulating apoptosis in maternal blood in severe early onset fetal growth restriction
C L Whitehead1, S P Walker, M Lappas
1Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, Heidelberg 3084, Victoria, Australia. clarew@unimelb.edu.au
Insights
Severe preterm fetal growth restriction (FGR) and pre-eclampsia (PE) show increased intrinsic apoptosis gene expression in placenta and maternal blood. Circulating RNAs may serve as novel biomarkers for FGR.
Area of Science:
- Reproductive Biology
- Genetics
- Biochemistry
Background:
- Fetal growth restriction (FGR) and pre-eclampsia (PE) are major obstetric complications.
- The intrinsic apoptosis pathway plays a role in placental development and function.
- Understanding molecular changes in FGR and PE is crucial for identifying biomarkers.
Purpose of the Study:
- To investigate differential expression of intrinsic apoptosis pathway genes in placenta and maternal blood in preterm FGR and PE.
- To explore the potential of circulating RNA in maternal blood as biomarkers for FGR.
Main Methods:
- Maternal blood and placental biopsies were collected from women with preterm FGR (n=20), PE without FGR (n=8), and controls (n=20).
- Real-time PCR was used to analyze the expression of intrinsic apoptosis pathway genes.
- Gene expression was stratified based on the severity of placental insufficiency.
Main Results:
- Severe preterm FGR (with or without PE) showed increased expression of BCL2, BCL-XL, BIM, BAD, and Survivin in placenta and maternal blood (1.6-3.3 fold, P<0.05).
- Preterm PE exhibited increased placental BCL-XL and BCL2 expression (1.6-2.5 fold, P<0.05), with only BCL2 significantly elevated in maternal blood (1.8 fold, P<0.05).
- Increased gene expression correlated with FGR severity indicated by umbilical artery Doppler velocimetry.
Conclusions:
- Severe early-onset FGR is characterized by upregulated intrinsic apoptosis genes in both placenta and maternal circulation.
- Circulating RNAs involved in placental apoptosis present potential as novel, non-invasive biomarkers for FGR detection.
Objective:
To determine whether the intrinsic apoptosis pathway is differentially expressed in placenta and maternal blood in severe preterm fetal growth restriction (FGR) and pre-eclampsia (PE), and to examine whether circulating RNA in maternal blood may be potential biomarkers.
Study Design:
Maternal blood samples and placental biopsies were collected from women with preterm: FGR (n=20), PE without FGR (n=8) and controls (n=20). Real-time PCR examined the expression of genes in the intrinsic apoptosis pathway in FGR and PE, stratified according to the severity of placental insufficiency.
Result:
Severe preterm FGR, with or without PE, was associated with increased expression of BCL2, BCL-XL, BIM, BAD and Survivin in both the placenta and maternal blood (1.6 to 3.3-fold, P<0.05). In preterm PE, but not FGR, there was increased placental expression of BCL-XL and BCL2 (1.6 to 2.5-fold, P<0.05), but only BCL2 was significantly increased in the maternal blood (1.8-fold, P<0.05). Increased expression of genes of the intrinsic apoptosis pathway reflected the severity of FGR as determined by deteriorations in umbilical artery Doppler velocimetry.
Conclusion:
In severe early onset FGR there was increased expression of genes regulating intrinsic apoptosis in both the placenta and maternal blood. Circulating RNA regulating placenta apoptosis may be used to develop noninvasive novel biomarkers for FGR.
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