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INO80 participates in the pathogenesis of recurrent miscarriage by epigenetically regulating trophoblast migration and invasion |
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| Authors: | Shu Xian Yan Zhang Li Wang Fang Yao Jinli Ding Yanqing Wang Xiao Yang Fangfang Dai Tailang Yin Yanxiang Cheng |
| Institution: | 1. Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, China;2. Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China
Contribution: Data curation (equal), Methodology (equal);3. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Contribution: Investigation (equal);4. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Contribution: Formal analysis (equal);5. Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, China Contribution: Formal analysis (equal);6. Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, China Contribution: Methodology (equal);7. Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, China;8. Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, China Contribution: Investigation (equal);9. Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, China |
| Abstract: | The INO80 complex, a SWI/SNF family chromatin remodeler, has regulatory effects on ESC self-renewal, somatic cell reprogramming and blastocyst development. However, the role of INO80 in regulating trophoblast cells and recurrent miscarriage (RM) remains elusive. To investigate the in vivo effects of Ino80 in embryo development, we disrupted Ino80 in C57 mice, which resulted in embryonic lethality. Silencing of Ino80 led to decreased survival capacity, migration and invasion of trophoblasts. Furthermore, RNA high-throughput sequencing (RNA-seq) revealed that Ino80 silencing closely resembled the gene expression changes in RM tissues. To investigate the mechanisms for these results, RNA-seq combined with high-throughput sequencing (ChIP-seq) was used in trophoblast cells, and it showed that Ino80 physically occupies promoter regions to affect the expression of invasion-associated genes. Last, Western blotting analyses and immunofluorescence staining revealed that the content of INO80 was reduced in RM patients compared to in healthy controls. This study indicates that INO80 has a specific regulatory effect on the viability, migration and invasion of trophoblast cells. Combined with its regulation of the expression of invasion-associated genes, it has been proposed that epigenetic regulation plays an important role in the occurrence of RM, potentially informing RM therapeutic strategies. |
| Keywords: | INO80 invasive recurrent miscarriage trophoblast |