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Elevated Expression of lncRNA MEG3 Induces Endothelial Dysfunction on HUVECs of IVF Born Offspring via Epigenetic
Ying Jiang1, Hong Zhu2,3, Hong Chen4
1Department of Obstetrics, School of Medicine, Women's Hospital, Zhejiang University, Hangzhou, China.
Insights
Children born via in vitro fertilization (IVF) may have higher blood pressure due to increased maternally expressed gene 3 (MEG3) expression, linked to epigenetic changes and cardiovascular risks.
Area of Science:
- Reproductive Medicine
- Epigenetics
- Cardiovascular Health
Background:
- Cardiovascular dysfunction in children born after in vitro fertilization (IVF) is a concern.
- Molecular mechanisms underlying these long-term outcomes remain unclear.
Purpose of the Study:
- To investigate the potential molecular mechanisms linking IVF conception to cardiovascular dysfunction in offspring.
- To explore the role of maternally expressed gene 3 (MEG3) in IVF offspring's cardiovascular health.
Main Methods:
- Compared blood pressure and gene expression in IVF offspring versus naturally conceived offspring.
- Analyzed expression of MEG3, eNOS, VEGF, and ET1 in endothelial cells and umbilical cord serum.
- Utilized pyrosequencing to assess MEG3 promoter methylation status.
Main Results:
- IVF offspring exhibited higher systolic blood pressure and elevated MEG3 expression in umbilical vein endothelial cells (HUVECs).
- MEG3 expression correlated with blood pressure and ET1/nitrate levels.
- Decreased eNOS/VEGF and increased ET1 expression were observed in IVF offspring's HUVECs and serum.
- Elevated MEG3 expression resulted from hypomethylation of its promoter.
Conclusions:
- Increased MEG3 expression, driven by promoter hypomethylation, presents a potential mechanism for hypertension risk in IVF offspring.
- Findings suggest epigenetic regulation of MEG3 plays a role in IVF-associated cardiovascular outcomes.
Abstract:
Cardiovascular dysfunction in children born after in vitro fertilization (IVF) has been of great concern, the potential molecular mechanisms for such long-term outcomes are still unknown. Here, we found that systolic blood pressure was a little higher in IVF born offspring at 2 years old compared to those born after being naturally conceived. Besides, the expression level of maternally expressed gene 3 (MEG3) was higher in human umbilical vein endothelial cells (HUVECs) from IVF offspring than that in spontaneously born offspring. Pearson correlation test showed that MEG3 relative expression is significantly related to the children's blood pressure (Coefficient = 0.429, P = 0.0262). Furthermore, we found decreased expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) along with elevated expression of endothelial-1(ET1) in HUVECs from IVF offspring, accompanied by lower secretion of nitrite, VEGF, and higher secretion of ET1 in the umbilical cord serum of IVF offspring. Correlation analysis showed MEG3 expression highly correlated with ET1 and Nitrate concentration. With pyrosequencing technology, we found that elevated expression of MEG3 was the result of hypomethylation of the MEG3 promoter. Therefore, our results provide a potential mechanism addressing the high-risk of hypertension in IVF offspring via MEG3 epigenetic regulation.
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