Aims: Assisted reproductive technologies (ART) have been widely used to treat infertility, which may impact on fetuses and offspring. This study investigated the effects of in vitro fertilization-embryo transfer (IVF-ET) on angiotensin II (AII)-mediated vasoconstrictions in umbilical cord vein, and explored possible reprogrammed methylation mechanism.
Materials and methods: Human umbilical cords were randomly divided into ordinary pregnancy and IVF-ET pregnancy. Vascular studies with AII as well as its specific receptor antagonists losartan and PD123,319 were conducted. Real-time quantitative PCR, Western blotting, and methylation analysis by bisulfite sequencing were performed with the cord vessel samples.
Key findings: In IVF-ET group, the maximal response to AII in umbilical vessels was significantly greater than that in the ordinary pregnancy. Using losartan and PD123,319, angiotensin receptor subtype 1 (AT1R) was found mainly responsible for the enhanced contraction in the umbilical vein of IVF-ET pregnancy. Decreased mRNA expression of DNMT3A was found in umbilical vein of IVF-ET group. Hypomethylation of the AGTR1 gene (gene encoding AT1R) in the umbilical veins of the IVF group was found. The data suggested that the IVF-ET treatments altered AII-mediated vasoconstrictions in umbilical veins, which could be partially attributed to the increased expression of AT1R.
Significance: The hypo-methylation of the AGTR1 gene caused by IVF-ET might play important roles in altered vasoconstrictions, impacting on cardiovascular systems in the long run.
Keywords: Angiotensin-II; In vitro fertilization-embryo transfer; Methylation; Umbilical cord vein; Vasoconstriction.
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