The Effect of Valproic Acid Application on Vasoactive Intestinal Peptide and Cyclooxygenase- 2 Activity in the Embryo Implantation Region

Objective: Epilepsy is an electrochemical brain dysfunction that affects millions of people today. Epilepsy disease has been associated with a high prevalence of reproductive disorders in men and women in the light of studies. It is known that valproic acid, an antiepileptic drug that is frequently prescribed for this disease that requires long-term treatment, adversely affects reproduction by causing apoptotic effects and folliculogenesis disorder in the ovary from pre-adolescence to adulthood. The aim of our study was to investigate the distribution of cyclooxygenase-2 (COX-2) and vasoactive intestinal peptide (VIP) molecules during embryo implantation in rats administered valproic acid (VPA). Method: 20 female rats were randomly divided into two groups, Group 1 was determined as Control, Group 2 as VPA Group. 1. Group; Saline s olution w as a dministered i ntraperitoneally i n t wo d oses f or 9 0 d ays. I n G roup 2 , 3 00 m g/kg/day V PA w as administered intraperitoneally in two doses for 90 days. Subjects were mated with male rats in a controlled cages and manner; mating day was accepted as day 0 and on day 7, the subjects were sacrificed under high-dose anesthesia and the tissues of the uterine implantation site were removed. Tissues were evaluated by immunohistochemistry and the findings were compared with statistical data. Results: In the immunohistochemical staining with COX-2 primary antibody, a strong immunoreaction was observed in the decidua, trophectoderm of the embryo and uterine gland epithelium in the sections belonging to the 7th day control group; On the sections in the 7th day of VPA group, the immunoreaction was observed to be weak in the same regions in staining with COX-2 antibody. In the another immunohistochemical staining with VIP primary antibody, immunoreaction of varying strength from weak to medium was observed in the decidua in the sections of the control group on the 7th day, moderate strength in the trophectoderm of the embryo, and weak to moderate immunoreaction in the uterine gland epithelium. On the 7th day, when the sections belonging to the VPA group were labeled with VIP antibody, an immunoreaction ranging from negative to weak was observed in the decidua, the trophectoderm of the embryo and the uterine gland epithelium. Conclusion: With the immunohistochemical evaluation and supporting statistical data in our study; Long-term use of VPA reduces the expression of COX-2 and VIP during pregnancy; It has been concluded that this decrease may adversely affect embryo implantation and thus the progression of pregnancy and pose a risk.