Polycomb subunit BMI1 determines uterine progesterone responsiveness essential for normal embryo implantation

Xin, Qiliang; Kong, Shuangbo; Yan, Junhao; Qiu, Jingtao; He, Bo; Zhou, Chan; Ni, Zhangli; Bao, Haili; Huang, Lin; Lu, Jinhua; Xia, Guoliang; Liu, Xi-Cheng; Chen, Zi-Jiang; Wang, Chao; Wang, Haibin

doi:10.1172/jci92862

Cited by 49 publications

(52 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PR antagonist RU486 injection in the peri‐implantation period hampers uterine PDS and embryo implantation in wild‐type (WT) mice . According to the previous literature, implantation failure occurs in all types of mice with impaired uterine PDS . PR has two isoforms, PR‐A and PR‐B.…”

Section: P4‐pr Signaling Controls Uterine Pds and Receptivitymentioning

confidence: 99%

“…A recent study of mouse models demonstrated that uterine ablation of the polycomb group gene BMI1, a component of the polycomb repressive complex‐1 (PRC1), induces implantation failure due to uterine P 4 responsiveness . BMI1 interacts with PR and E3 ligase E6AP in a polycomb complex‐independent manner and controls PR ubiquitination . In women who had a spontaneous miscarriage, low BMI1 expression in endometrium is correlated with poor PR responsiveness .…”

Section: Appropriate Balance Between E2 and P4 Is Necessary For Uterimentioning

confidence: 99%

“…BMI1 interacts with PR and E3 ligase E6AP in a polycomb complex‐independent manner and controls PR ubiquitination . In women who had a spontaneous miscarriage, low BMI1 expression in endometrium is correlated with poor PR responsiveness . Thus, BMI1 controls uterine PR function under the post‐transcriptional modification and contributes to successful embryo implantation in mice and humans (Figure ).…”

Section: Appropriate Balance Between E2 and P4 Is Necessary For Uterimentioning

confidence: 99%

See 2 more Smart Citations

Uterine receptivity, embryo attachment, and embryo invasion: Multistep processes in embryo implantation

Fukui

Hirota

Matsuo

et al. 2019

Reprod Medicine & Biology

View full text Add to dashboard Cite

Background Recurrent implantation failure is a critical issue in IVF‐ET treatment. Successful embryo implantation needs appropriate molecular and cellular communications between embryo and uterus. Rodent models have been used intensively to understand these mechanisms. Methods The molecular and cellular mechanisms of embryo implantation were described by referring to the previous literature investigated by us and others. The studies using mouse models of embryo implantation were mainly cited. Results Progesterone (P4) produced by ovarian corpus luteum provides the uterus with receptivity to the embryo, and uterine epithelial growth arrest and stromal proliferation, what we call uterine proliferation‐differentiation switching (PDS), take place in the peri‐implantation period before embryo attachment. Uterine PDS is a hallmark of uterine receptivity, and several genes such as HAND2 and BMI1, control uterine PDS by modulating P4‐PR signaling. As the next implantation process, embryo attachment onto the luminal epithelium occurs. This process is regulated by FOXA2‐LIF pathway and planar cell polarity signaling. Then, the luminal epithelium at the embryo attachment site detaches from the stroma, which enables trophoblast invasion. This process of embryo invasion is regulated by HIF2α in the stroma. Conclusion These findings indicate that embryo implantation contains multistep processes regulated by specific molecular pathways.

show abstract

Section: P4‐pr Signaling Controls Uterine Pds and Receptivitymentioning

confidence: 99%

Section: Appropriate Balance Between E2 and P4 Is Necessary For Uterimentioning

confidence: 99%

Section: Appropriate Balance Between E2 and P4 Is Necessary For Uterimentioning

confidence: 99%

See 1 more Smart Citation

Uterine receptivity, embryo attachment, and embryo invasion: Multistep processes in embryo implantation

Fukui

Hirota

Matsuo

et al. 2019

Reprod Medicine & Biology

View full text Add to dashboard Cite

show abstract

“…Recently the interaction of BMI1 with the progesterone receptor (PR) was described. Together with the E3 ligase and in a PRC1-independent manner BMI1 modulates the response capacity of the PR in the uterus allowing embryonic implantation in human and mouse models (Xin et al, 2018). In this project, Bmi1 and Ezh2 downregulation suggest that modification of chromatin structure may coordinate the effect of the FA in the ovary.…”

Section: Discussionmentioning

confidence: 67%

“…In the ovary, BMI1 is expressed in a high percentage of ovarian epithelial cells (OEC), and it is associated with advanced cancer stage and higher grades of carcinomas (Abd El Hafez and El-Hadaad, 2014). However, recently BMI1 has been studied due to its interaction with the P4 receptor (PR) regulating uterine P4 responsiveness in mice (Xin et al, 2018). Moreover, this role has been conserved from mouse to human, since there was a close association with loss of BMI1 and PR sensitivity in the endometrium of miscarrying women in the same study.…”

Section: Prc1: Bmi1mentioning

confidence: 99%

The Effect of Folic Acid Supplementation in the Ovary and Upon Embryo Development

et al. 2019

View full text Add to dashboard Cite

Faculty of Natural and Environmental Sciences School of Biological Sciences Thesis for the degree of Doctor of Philosophy The Effect of Folic Acid Supplementation in the Ovary and Upon Embryo Development by Reyna Stephanie Penailillo Escarate Altered maternal nutrition around conception can affect oocyte and embryo development which influences later-life health outcomes. Low folate is related to poor reproductive outcomes. Folic acid (FA) supplementation and fortification have been effective strategies to avoid NTD. On the other hand, the FA levels in women of reproductive age are increased more than recommended, with unknown consequences. This project aims to determine the effect of high FA diet on the

show abstract

Excessive Lipid Peroxidation in Uterine Epithelium Causes Implantation Failure and Pregnancy Loss

Lu,

Shao,

Cui

et al. 2023

Advanced Science

Self Cite

View full text Add to dashboard Cite

The uterine epithelium undergoes a dramatic spatiotemporal transformation to enter a receptive state, involving a complex interaction between ovarian hormones and signals from stromal and epithelial cells. Redox homeostasis is critical for cellular physiological steady state; emerging evidence reveals that excessive lipid peroxides derail redox homeostasis, causing various diseases. However, the role of redox homeostasis in early pregnancy remains largely unknown. It is found that uterine deletion of Glutathione peroxidase 4 (GPX4), a key factor in repairing oxidative damage to lipids, confers defective implantation, leading to infertility. To further pinpoint Gpx4’s role in different cell types, uterine epithelial‐specific Gpx4 is deleted by a lactotransferrin (Ltf)‐Cre driver; the resultant females are infertile, suggesting increased lipid peroxidation levels in uterine epithelium compromises receptivity and implantation. Lipid peroxidation inhibitor administration failed to rescue implantation due to carbonylation of major receptive‐related proteins underlying high lipid reactive oxygen species. Intriguingly, superimposition of Acyl‐CoA synthetase long‐chain family member 4 (ACSL4), an enzyme that promotes biosynthesis of phospholipid hydroperoxides, along with uterine epithelial GPX4 deletion, preserves reproductive capacity. This study reveals the pernicious impact of unbalanced redox signaling on embryo implantation and suggests the obliteration of lipid peroxides as a possible therapeutic approach to prevent implantation defects.

show abstract

Polycomb subunit BMI1 determines uterine progesterone responsiveness essential for normal embryo implantation

Cited by 49 publications

References 49 publications

Uterine receptivity, embryo attachment, and embryo invasion: Multistep processes in embryo implantation

Uterine receptivity, embryo attachment, and embryo invasion: Multistep processes in embryo implantation

The Effect of Folic Acid Supplementation in the Ovary and Upon Embryo Development

Excessive Lipid Peroxidation in Uterine Epithelium Causes Implantation Failure and Pregnancy Loss

Contact Info

Product

Resources

About