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

Mengying Liu, Wenbo Deng, Lu Tang, Meng Liu, Haili Bao, Chuanhui Guo, Changxian Zhang, Jinhua Lu, Haibin Wang (), Zhongxian Lu () and Shuangbo Kong ()
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Mengying Liu: Xiamen University
Wenbo Deng: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University
Lu Tang: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University
Meng Liu: Xiamen University
Haili Bao: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University
Chuanhui Guo: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University
Changxian Zhang: Université Lyon 1
Jinhua Lu: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University
Haibin Wang: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University
Zhongxian Lu: Xiamen University
Shuangbo Kong: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28657-2

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