Investigation of the efficacy of TRPC1 ion channel inhibition with nifedipine in the prevention of ovarian hyperstimulation: Experimental Study

In this study, the effectiveness of TRPC1 ion channel inhibition with Nifedipine in preventing ovarian hyperstimulation was investigated. In the study, severe ovarian hyperstimulation was created by administering 30 IU pregnant mare serum gonadotropin (PMSG) subcutaneously for four days and 30 IU human chorionic gonadotropin on the fifth day to 7 randomly selected rats between 28 female Spraque - Dawley albino rats weighing 45-60 g, 22-23 days old. Rats was divided into four groups as Group 1 (n=7) had 27 days of normal, Group 2 (n=7) had severe OHSS for 27 days, Group 3 (n=7) had severe OHSS and was given cabergoline on the HCG day and Group 4 (n=7) had severe OHSS and was given nifedipine on the HCG day. Then, ovaries and blood samples of all groups were taken and the rats were sacrificed. VEGF, HIF-1α, IL 1-, IL-6, TNF-α levels in serum VEGF, HIF-1α, IL 1-, IL-6, TNF-α levels in tissue and TRPC-1 activity were measured. As a result of our study, we showed that nifedipine, like cabergoline, not only reduces VEGF levels in serum and ovarian tissue, but also reduces OHSS formation by lowering proinflammatory cytokine levels. Nifedipine may have these effects through TRPC1 ion channel blockade. In our study, TRPC1 immunoreactivity increased in OHSS. Additionally, this study showed that cabergoline could not suppress TRPC1 immunoreactivity, while nifedipine significantly reduced TRPC1 immunoreactivity. It was observed that TRPC1 gene expression decreased in the OHSS and cabergoline treatment group. Besides, although there was a significant decrease in TRPC1 gene expression in the nifedipine group compared to the control group, a significant increase in gene expression was detected compared to the OHSS and Cabergoline groups. In our study, serum and tissue VEGF levels were observed to increase significantly in the OHSS group compared to the control group. Also, it was observed that cabergoline and nifedipine significantly reduced serum and tissue VEGF levels at a similar rate compared to the OHSS group. If we look at serum and tissue HIF-1 levels among all groups, no significant difference was detected between the groups. In our study, we found that serum IL-1ẞ, IL-6 and TNF levels in OHSS group were higher according to the control group. We showed that nifedipine significantly reduced IL-1, IL-6 and TNF levels. While tissue IL-1 values were higher in OHSS group comparing to the control group, no difference was observed between OHSS, cabergoline and nifedipine groups. Tissue IL-6 and TNF levels were similar between the OHSS and control groups. Nevertheless, IL-6 levels of the nifedipine and cabergoline groups were less than the OHSS group. When tissue TNF-α levels were compared, there was no significant difference in tissue TNF-α levels between the control group and the OHSS group. When tissue TNF- α levels between the OHSS and cabergoline groups were compared, it was found that tissue TNF- α level in cabergoline group is significantly lower than the OHSS group. When the cabergoline and nifedipine groups were compared, no significant difference was detected between these two groups. We showed that nifedipine, as an anti-inflammatory effect, significantly reduced serum inflammatory cytokines IL-1, IL-6 and TNF-α levels in rats with OHSS. The conclusion we get from our study is that nifedipine reduces the development of OHSS by suppressing the production of pro-inflammatory cytokines such as IL-1, IL-6, TNF-α, as well as VEGF, probably through inhibition of TRPC1 channel activity.