The Novel Anti-Inflammatory Mechanism of Calcitriol in Recurrent Spontaneous Abortion in Experimental Mice

Background: In many instances, Recurrent Spontaneous Abortion (RSA) has unexplained etiology and does not have any prognostic clues. Antioxidant vitamins are closely related to a series of diseases, including RSA. However, the function and underlying mechanism of calcitriol in the treatment of RSA has not been described. Materials and Methods: The pregnant mice were injected intraperitoneally with Lipopolysaccharide (LPS) to induce abortion. Calcitriol was used for the treatment and to avoid RSA. Pathological analysis was done to assess the abnormalities during RSA and its treatment using calcitriol. Results: After LPS administration, the mice exhibited high embryo absorption and pathological alterations, as well as, presented an increase in inflammation and apoptosis. Moreover, higher levels of NF-κB and inflammatory cytokines (TNF and IL-6) were noticed in serum and in isolated macrophages. Furthermore, we found alterations in the Nrf2 levels, enzymatic antioxidants and non-enzymatic antioxidants in serum. All these abnormalities were attenuated during calcitriol treatment in the appropriate groups of mice. Conclusion: Our results indicate that calcitriol may be involved in the modulation of inflammatory signaling and NF-κB pathway-mediated inflammation in RSA. Therefore, calcitriol could serve as a better prognostic regimen in the RSA treatment.