DNA hypomethylation in villi of patients with unexplained recurrent spontaneous abortion and its mechanism

: Objective To explore the genome-wide DNA methylation level and the expression of DNA methylation-related enzymes in the villi tissue of patients with unexplained recurrent spontaneous abortion (URSA). Methods The villi samples were obtained from thirty-one URSA patients (URSA group) and thirty pregnancy women who underwent induced abortion (control group). Total DNA methylation was determined by ELISA. Real-time quantitative PCR was used to detect mRNA levels of DNMT1, DNMT3a, DNMT3b, TET1, TET2 and TET3, and Western blot analysis was used to detect protein levels of DNMT1, DNMT2, DNMT3, TET1, TET2 and TET3. Immunohistochemistry was performed to detect the expression and distribution of DNMT1, DNMT3a, DNMT3b, TET1, TET2 and TET3 in villi tissues. Results Methylation level of total DNA in the URSA group was significantly lower than that of the control group. Compared with the control group, mRNA and protein expression levels of DNMT1 and DNMT3b significantly decreased, while TET1 and TET2 significantly increased in the villi of the URSA group. Conclusion The methylation level is reduced in the villi of URSA women, which may be correlated with up-regulated expression of DNMT1 and DNMT3b and down-regulated expression of TET1 and TET2.