Immunohistochemical analysis of the effect of preconceptional folic acid supplementation on embryonic implantation in rats

Implantation is one of the important stages in pregnancy formation. With the improvements in assisted reproductive techniques, implantation failures have started to come to the fore among the causes of infertility. Implantation takes place in a short period of interaction between the uterine endometrium and the embryo. In this process, the embryo and endometrium must be ready for implantation. The implantation process is mediated by many molecules expressed in the endometrium and embryo. Folic acid (FA) is a vitamin recommended to be used as a supplement before pregnancy occurs, and its deficiency can cause congenital anomalies. There are recommendations for use in different doses during pregnancy. In this study, it was aimed to evaluate the relationship of folic acid with embryo implantation. In our study, 32 female wistar albino rats, 6-8 weeks old, were used. The rats were divided into 4 groups as control, deficiency model was created, low dose (5mg/kg) FA supplement was given, and high dose (40mg/kg) FA supplement was given. After 5 weeks of supplementation and deficiency pattern formation, females mated with male rats were sacrificed and implantation sites were collected for implantation evaluation on day 5 following mating. Tissues taken were comparatively evaluated histologically and at the level of gene expression. In the groups evaluated for vascular endothelial growth factor-A (VEGF-A), Estrogen Receptor-alpha (ER-α), integrin αVβ3, all markers were significantly decreased in the deficiency group, while in the low-dose and high-dose groups, an increase was observed in all markers with IHC and RT-PCR. As a result of our study, it has been revealed that supplementation of folic acid before pregnancy has positive effects in the formation and maintenance of pregnancy as well as other known neonatal effects, and its deficiency may lead to disorders in the implantation stage. The effects on implantation can be revealed more clearly with future pathway studies.