A research group at Nagoya University and Nagoya City University has discovered, for the first time in the world, that the pattern of DNA methylation differs from that of normal pregnancies in villi (derived from the fetus) of patients with unexplained recurrent miscarriages.
Three or more consecutive miscarriages, defined as recurrent miscarriages, have a prevalence of 3%, but the cause remains unknown in about 1.1% of cases.In today's world of declining birthrates, investigating the causes and preventing recurrent miscarriages is an urgent issue.
In normal embryonic development, dynamic changes in DNA methylation (chemical modification of DNA) occur in the early stages after fertilization, and it is clear that differentiation and growth into various tissues occur.Focusing on this point, in this study, we performed a comprehensive DNA methylation analysis of fetal-derived villi and maternal-derived decidua that constitute placental tissue.
As a result, by hierarchical cluster analysis, we found that the pattern of DNA methylation was different between the recurrent abortion group and the normal pregnancy group in fetal-derived villi but not maternal-derived decidua.In addition, when we extracted genes with large differences in DNA methylation between the recurrent abortion group and the normal pregnancy group, we succeeded in identifying SPATS2L as a representative gene.
Therefore, when we examined the expression of SPATS2L in villous tissues, we found that the expression of SPATS2L protein decreased in the cytoplasm of cytotrophoblast cells that constitute the inner side of the chorion in the recurrent abortion group.Artificial suppression (knockdown) of SPATS2L in a trophoblast cell line reduced the invasive and migratory abilities of trophoblast cells, suggesting that decreased SPATS2L protein expression may inhibit normal embryonic development. I think there is
These results suggest that abnormal DNA methylation in villi may be one of the causes of recurrent abortion.However, since all five recurrent miscarriage patients analyzed in this study were able to have live babies afterward, it is expected that recurrent miscarriage patients with DNA methylation abnormalities will later have live births. It is said that it is possible to explain that it can be done.
Paper information:[Scientific Reports] Characteristic DNA methylation profiles of chorionic villi in recurrent miscarriages