2. Academic Validation
  3. Menin directs regionalized decidual transformation through epigenetically setting PTX3 to balance FGF and BMP signaling

Menin directs regionalized decidual transformation through epigenetically setting PTX3 to balance FGF and BMP signaling

  • Nat Commun. 2022 Feb 22;13(1):1006. doi: 10.1038/s41467-022-28657-2.
Mengying Liu  # 1 2,  Wenbo Deng  # 2,  Lu Tang 2,  Meng Liu 1,  Haili Bao 2,  Chuanhui Guo 2,  Changxian Zhang 3,  Jinhua Lu 2,  Haibin Wang 4,  Zhongxian Lu 5 6,  Shuangbo Kong 7
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China.
  • 2 Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
  • 3 Centre de Recherche en Cancérologie de Lyon, Université Lyon 1, Inserm U1052, CNRS UMR5286, Lyon, F-69000, France.
  • 4 Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China. haibin.wang@vip.163.com.
  • 5 School of Pharmaceutical Sciences, State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, Fujian, China. zhongxian@xmu.edu.cn.
  • 6 Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China. zhongxian@xmu.edu.cn.
  • 7 Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China. shuangbo_kong@163.com.
  • # Contributed equally.
PMID: 35194044 DOI: 10.1038/s41467-022-28657-2
Abstract

During decidualization in rodents, uterine stroma undergoes extensive reprograming into distinct cells, forming the discrete regions defined as the primary decidual zone (PDZ), the secondary decidual zone (SDZ) and the layer of undifferentiated stromal cells respectively. Here we show that uterine deletion of Men1, a member of the histone H3K4 methyltransferase complex, disrupts the terminal differentiation of stroma, resulting in chaotic decidualization and pregnancy failure. Genome-wide epigenetic profile reveals that Men1 binding in chromatin recapitulates H3K4me3 distribution. Further transcriptomic investigation demonstrates that Men1 directly regulates the expression of PTX3, an extra-cellular trap for FGF2 in decidual cells. Decreased Ptx3 upon Men1 ablation leads to aberrant activation of ERK1/2 in the SDZ due to the unrestrained FGF2 signal emanated from undifferentiated stromal cells, which blunt BMP2 induction and decidualization. In brief, our study provides genetic and molecular mechanisms for epigenetic rewiring mediated decidual regionalization by Men1 and sheds new light on pregnancy maintenance.

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