Characteristic DNA methylation profiles of chorionic villi in recurrent miscarriage
Abstract Dysregulation 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 patient...
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| Format: | Article |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-15656-y |
| _version_ | 1828189861576704000 |
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| author | Yosuke Matsumoto Keiko Shinjo Shoko Mase Masaki Fukuyo Kosuke Aoki Fumiko Ozawa Hiroyuki Yoshihara Shinobu Goto Tamao Kitaori Yasuhiko Ozaki Satoru Takahashi Atsushi Kaneda Mayumi Sugiura-Ogasawara Yutaka Kondo |
| author_facet | Yosuke Matsumoto Keiko Shinjo Shoko Mase Masaki Fukuyo Kosuke Aoki Fumiko Ozawa Hiroyuki Yoshihara Shinobu Goto Tamao Kitaori Yasuhiko Ozaki Satoru Takahashi Atsushi Kaneda Mayumi Sugiura-Ogasawara Yutaka Kondo |
| author_sort | Yosuke Matsumoto |
| collection | DOAJ |
| description | Abstract Dysregulation 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. |
| first_indexed | 2024-04-12T08:11:39Z |
| format | Article |
| id | doaj.art-dc97a24747dd464fa56b181f2fad7c10 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T08:11:39Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dc97a24747dd464fa56b181f2fad7c102022-12-22T03:40:56ZengNature PortfolioScientific Reports2045-23222022-07-0112111110.1038/s41598-022-15656-yCharacteristic DNA methylation profiles of chorionic villi in recurrent miscarriageYosuke Matsumoto0Keiko Shinjo1Shoko Mase2Masaki Fukuyo3Kosuke Aoki4Fumiko Ozawa5Hiroyuki Yoshihara6Shinobu Goto7Tamao Kitaori8Yasuhiko Ozaki9Satoru Takahashi10Atsushi Kaneda11Mayumi Sugiura-Ogasawara12Yutaka Kondo13Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical SciencesDivision of Cancer Biology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical SciencesDepartment of Molecular Oncology, Graduate School of Medicine, Chiba UniversityDepartment of Neurosurgery, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical SciencesDepartment of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical SciencesDepartment of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical SciencesDepartment of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical SciencesDepartment of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical SciencesDepartment of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical SciencesDepartment of Molecular Oncology, Graduate School of Medicine, Chiba UniversityDepartment of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical SciencesDivision of Cancer Biology, Nagoya University Graduate School of MedicineAbstract Dysregulation 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.https://doi.org/10.1038/s41598-022-15656-y |
| spellingShingle | Yosuke Matsumoto Keiko Shinjo Shoko Mase Masaki Fukuyo Kosuke Aoki Fumiko Ozawa Hiroyuki Yoshihara Shinobu Goto Tamao Kitaori Yasuhiko Ozaki Satoru Takahashi Atsushi Kaneda Mayumi Sugiura-Ogasawara Yutaka Kondo Characteristic DNA methylation profiles of chorionic villi in recurrent miscarriage Scientific Reports |
| title | Characteristic DNA methylation profiles of chorionic villi in recurrent miscarriage |
| title_full | Characteristic DNA methylation profiles of chorionic villi in recurrent miscarriage |
| title_fullStr | Characteristic DNA methylation profiles of chorionic villi in recurrent miscarriage |
| title_full_unstemmed | Characteristic DNA methylation profiles of chorionic villi in recurrent miscarriage |
| title_short | Characteristic DNA methylation profiles of chorionic villi in recurrent miscarriage |
| title_sort | characteristic dna methylation profiles of chorionic villi in recurrent miscarriage |
| url | https://doi.org/10.1038/s41598-022-15656-y |
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