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Journal of Assisted Reproduction and Genetics
Published in: Journal of Assisted Reproduction and Genetics 5/2020

01-05-2020 | Reproductive Physiology and Disease

The role and mechanism of asymmetric dimethylarginine in fetal growth restriction via interference with endothelial function and angiogenesis

Authors: Yan Dai, Jun Zhang, Rong Liu, Na Xu, Song-Biao Yan, Yi Chen, Tian-He Li

Published in: Journal of Assisted Reproduction and Genetics | Issue 5/2020

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Abstract

Purpose

Fetal growth restriction (FGR) is a high-risk pregnancy, and placental dysfunction is the main cause of FGR. The upregulation of asymmetric dimethylarginine (ADMA) is linked to FGR pathology, but the mechanism needs to be investigated.

Methods

The levels of ADMA and other related molecules were measured in human biological samples. We further used human umbilical vein endothelial cells (HUVECs) to reveal the mechanism of ADMA-induced FGR in vitro.

Results

Compared with the control group, FGR patients had higher placental resistance, and ADMA levels were increased in the maternal blood, cord blood, and placenta; additionally, nitric oxide (NO) production decreased, accompanied by a decreased expression of endogenous NO synthase (eNOS). The expression of vascular growth factor (VEGF) and placental growth factor (PLGF) in the maternal blood during the third trimester and umbilical cord of the FGR group was lower than the control group. The PLGF levels in the placentas of the FGR group were also reduced, while the expression of soluble fms-like tyrosine kinase-1 (sFlt-1) increased. In in vitro cell experiments, NO production was obviously lower when the cells were exposed to 100 μM of ADMA, with no difference in eNOS expression. There was a dose-dependent decrease in PLGF expression with increasing doses of ADMA, and the levels of sFlt-1 increased. Moreover, we confirmed that tube formation in HUVECs was lower after ADMA treatment compared with the control group.

Conclusion

The accumulation of ADMA during pregnancy has an adverse effect on fetal development via interference with placental endothelial function and angiogenesis.
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Metadata
Title
The role and mechanism of asymmetric dimethylarginine in fetal growth restriction via interference with endothelial function and angiogenesis
Authors
Yan Dai
Jun Zhang
Rong Liu
Na Xu
Song-Biao Yan
Yi Chen
Tian-He Li
Publication date
01-05-2020
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 5/2020
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-020-01750-5

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