2. Academic Validation
  3. MAX deficiency impairs human endometrial decidualization through down-regulating OSR2 in women with recurrent spontaneous abortion

MAX deficiency impairs human endometrial decidualization through down-regulating OSR2 in women with recurrent spontaneous abortion

  • Cell Tissue Res. 2022 May;388(2):453-469. doi: 10.1007/s00441-022-03579-z.
Weixu Ma 1 2,  Mingzhu Cao 1 2,  Shilei Bi 3 4 5 6,  Lili Du 3 4 5 6,  Jingsi Chen 3 4 5 6,  Haibin Wang 7 8,  Yufei Jiang 9,  Yixuan Wu 1 2,  Yixin Liao 10,  Shuangbo Kong 11 12,  Jianqiao Liu 13 14
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 2 Key Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 3 Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 4 Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Guangzhou, China.
  • 5 Guangdong Engineering and Technology Research Center of Maternal-Fetal Medicine, Guangzhou, China.
  • 6 Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, Guangzhou, China.
  • 7 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China.
  • 8 Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, China.
  • 9 Xiamen Key Laboratory of Reproduction and Genetics, Department of Reproductive Medicine, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China.
  • 10 Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 11 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, China. shuangbo_kong@163.com.
  • 12 Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, China. shuangbo_kong@163.com.
  • 13 Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. liujqssz@gzhmu.edu.cn.
  • 14 Key Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. liujqssz@gzhmu.edu.cn.
PMID: 35146559 DOI: 10.1007/s00441-022-03579-z
Abstract

Human uterine stromal cell undergoes decidualization for pregnancy establishment and maintenance, which involved extensive proliferation and differentiation. Increasing studies have suggested that recurrent spontaneous abortion (RSA) may result from defective endometrial stromal decidualization. However, the critical molecular mechanisms underlying impaired decidualization during RSA are still elusive. By using our recently published single-cell RNA sequencing (scRNA-seq) atlas, we found that MYC-associated factor X (MAX) was significantly downregulated in the stromal cells derived from decidual tissues of women with RSA, followed by verification with immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR). MAX knockdown significantly impairs human endometrial stromal cells (HESCs) proliferation as determined by MTS assay and Ki67 immunostaining, and decidualization determined by F-actin, and decidualization markers. RNA-seq together with chromatin immunoprecipitation sequencing (ChIP-seq) and cleavage under targets and release using nuclease sequencing (CUT&RUN-seq) analysis were applied to explore the molecular mechanisms of MAX in regulation of decidualization, followed by dual-luciferase reporter assay to verify that MAX targets to (odd-skipped related transcription factor 2) OSR2 directly. Reduced expression of OSR2 was also confirmed in decidual tissues in women with RSA by IHC and qRT-PCR. OSR2 knockdown also significantly impairs HESCs decidualization. OSR2-overexpression could at least partly rescue the downregulated insulin-like growth factor binding protein 1 (IGFBP1) expression level in response to MAX knockdown. Collectively, MAX deficiency observed in RSA stromal cells not only attenuates HESCs proliferation but also impairs HESCs decidualization by downregulating OSR2 expression at transcriptional level directly.

Keywords

Decidualization; Human endometrial stromal cells (HESCs); MYC-associated factor X (MAX); Odd-skipped related transcription factor 2 (OSR2); Recurrent spontaneous abortion (RSA).

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