The effect of folic acid supplementation and folate deficiency on embryo implantation

Implantation is a critical stage of pregnancy, which occurs in a short period of interaction between the receptive endometrium and the embryo. Folic acid (FA) is a synthetic derivative of folate and is recommended as a pre-conceptional supplement. However, the impact of different doses of FA supplementation and folate deficiency during the early stages of pregnancy requires further investigation. The aim of this study was to investigate the possible effects of FA supplementation and folate deficiency on expression of Estrogen Receptor Alpha (ER-α), Vascular Endothelial Growth Factor-A (VEGFA), and Integrin alpha V and beta3 (Integrin αVβ3). A total of 32, 6–8-week old Wistar albino rats were divided into four groups of control, folate-deficiency, low-dose, and high-dose FA supplement groups. After five weeks of FA supplementation and folate deficiency model formation, mated rats were sacrificed on the 5th gestational day (GD), and implantation sites were collected. The expression of ER- α, VEGFA, and Integrin αVβ3 in the implantation sites were examined with immunohistochemistry and real-time PCR. The results revealed that the mRNA levels of ESR1, VEGFA, and Integrin αV and β3 were significantly increased in the high-dose FA group and significantly decreased in the folate deficiency group compared to the control group (p < 0.05). Based on these results, it can be concluded that FA supplementation before pregnancy has positive effects on the maintenance of pregnancy, and folate deficiency may lead to implantation disorders.