Placental expression and methylation of angiogenic factors in assisted reproductive technology pregnancies from India.

Aim: This study aims to examine the gene expression and DNA methylation patterns of angiogenic factors in the placentae of Indian women who underwent assisted reproductive technology (ART) procedures and their association with maternal one-carbon metabolites and birth outcome.

Methods: Placental gene expression and DNA methylation of angiogenic factors (VEGF, PlGF, FLT-1, KDR) in Indian women who underwent ART procedures (n = 64) and women who conceived naturally (Non-ART) (n = 93) was investigated using RT-qPCR and Epitect Methyl-II PCR assay kits. Maternal plasma one-carbon metabolites were assessed by CMIA technology.

Result: Gene expression of FLT-1 and KDR was higher (p < 0.05) in the ART placentae. Placental global DNA methylation levels were higher (p < 0.01) and DNA methylation levels of VEGF promoter were lower (p < 0.05) in ART compared to non-ART women. Maternal plasma folate and vitamin B₁₂ levels were higher (p < 0.01) in the ART group. Gene expression of PlGF was negatively associated with maternal plasma folate (p < 0.05) whereas KDR was positively associated with maternal plasma homocysteine (p < 0.05). Gene expression of KDR was positively associated with chest circumference of the baby (p < 0.05).

Conclusion: Hypomethylation of VEGF and increased expression of FLT-1 and KDR was observed in the placentae of women who underwent ART procedure.