The Role of Human Endogenous Retroviruses, TRIM28 and SETDB1 in improving the course of Multiple Sclerosis during gestation.

Emerging evidence emphasizes the role of human endogenous retroviruses (HERVs) in the development and persistence of multiple sclerosis (MS). The activation of HERVs and associated neuroinflammatory disorders, including MS, involves epigenetic mechanisms regulated by TRIM28 and SETDB1. While pregnancy has been shown to significantly improve the course of MS, there is a lack of research on the expression of HERVs, TRIM28, and SETDB1 during gestation. In this study, we utilized a polymerase chain reaction real-time Taqman amplification assay to examine and compare the transcriptional levels of specific genes related to HERVs (HERV-H, HERV-K, HERV-W), Syncytin (SYN) genes (SYN1, SYN2), multiple sclerosis-associated retrovirus (MSRV), as well as TRIM28 and SETDB1 in peripheral blood and placental samples from 20 mothers with MS, cord blood samples from 27 healthy mothers, and blood samples from healthy women of child-bearing age. We found that HERV mRNA levels were significantly lower in pregnant women compared to nonpregnant women. Moreover, the expressions of all HERVs were downregulated in the chorion and decidua basalis of MS mothers compared to healthy mothers. MS mothers also exhibited lower mRNA levels of HERV-K-pol, SYN1, SYN2, and MSRV in peripheral blood. In addition, the expressions of TRIM28 and SETDB1 were significantly reduced in pregnant women compared to nonpregnant women, as well as in the blood, chorion, and decidua of MS mothers compared to healthy mothers. However, there were no significant differences in HERV and TRIM28/SETDB1 expressions between neonates of MS mothers and healthy mothers. These findings indicate that gestation is characterized by impaired expressions of HERVs and TRIM28/SETDB1, particularly in mothers with MS. Considering the positive effects of pregnancy on MS and the existing data suggesting the potential contribution of HERVs and epigenetic processes to the disease's pathogenesis, our results provide further support for innovative therapeutic interventions that target HERV activation and abnormal epigenetic pathways in individuals affected by MS.