Author:
Matsumoto Yosuke,Shinjo Keiko,Mase Shoko,Fukuyo Masaki,Aoki Kosuke,Ozawa Fumiko,Yoshihara Hiroyuki,Goto Shinobu,Kitaori Tamao,Ozaki Yasuhiko,Takahashi Satoru,Kaneda Atsushi,Sugiura-Ogasawara Mayumi,Kondo Yutaka
Abstract
AbstractDysregulation of transcriptional programs that are tightly regulated by DNA methylation during placental and fetal development at different gestational stages, may cause recurrent miscarriage. Here, we examined genome-wide DNA methylation in chorionic villi and decidual tissues from patients suffering RM and from healthy women who had undergone artificial abortion (n = 5 each). We found that 13,426 and 5816 CpG sites were differentially methylated in chorionic villi and decidua, respectively. DNA methylation profiles of chorionic villi, but not decidua, in RM patients was clearly distinct from AA controls. Among the differentially methylated genes, the enhancer region of SPATS2L was significantly more highly methylated in RM patients (n = 19) than AA controls (n = 19; mean methylation level, 52.0%-vs.-28.9%, P < 0.001), resulting in reduced expression of SPATS2L protein in the former. Functionally, depletion of SPATS2L in extravillous trophoblast cells decreased their invasion and migration abilities. Our data indicate that particularly the chorionic villi in RM patients exhibit distinct DNA methylation profiles compared with normal pregnancies and that this changed DNA methylation status may impede the progression of embryo development via the altered expression of genes such as SPATS2L in the villi.
Funder
Japan Society for the Promotion of Science
Ministry of Education, Culture, Sports, Science and Technology
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
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