Abnormally increased DNA methylation in chorionic tissue might play an important role in development of ectopic pregnancy

Abstract

Background: Human Ectopic Pregnancy (hEP) is the second most common cause of pregnancy-related deaths in the first trimester. Without timely detection, EPs can lead to an increased rate of infertility and an elevated risk for future tubal EPs. In addition, most studies in the field focus on the effect of the fallopian tube (maternal factors) and ignore epigenetic changes in genes and proteins of the embryo, which may also cause EPs. Therefore, the present study hypothesized that embryos also play an important role in the development of EP. The study also speculated that DNA methylation is associated with ectopic pregnancy. Consequently, the effects of DNA methylation on the occurrence and development of ectopic pregnancy were investigated. Moreover, genome-wide DNA methylation of chorionic tissue from ectopic and intrauterine pregnancies was detected using Illumina HumanMethylation450 arrays. Results: Forty-three hypermethylated genes involved in the regulation of adhesion as well as gene transcription and translation were identified. Furthermore, the PPI network showed that AMOTL1, SDR42E1, CAMTA1, PIP5K1C, KIAA1614, TSTD1 and DNER may play important roles in the occurrence and development of ectopic pregnancy. In addition, SDR42E1, CAMTA1 and TSTD1 displayed higher levels of methylation in ectopic pregnancy while PIP5K1C and DNER showed low degrees of methylation. Conclusions: The study reveals that abnormal increase in methylation may be an early indicator or an inducer of ectopic pregnancy. In addition, AMOTL1, SDR42E1, CAMTA1, PIP5K1C, KIAA1614, TSTD1 and DNER might play important roles in the occurrence and development of ectopic pregnancy. However, the specific molecular mechanisms are still unclear and require further studies.