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Blastocyst-induced ATP release from luminal epithelial cells initiates decidualization through the P2Y2 receptor in mice

Gu, Xiao Wei ; Chen, Zi Cong ; Yang, Zhen Shan LU orcid ; Yang, Yan ; Yan, Ya Ping ; Liu, Yue Fang ; Pan, Ji Min ; Su, Ren Wei and Yang, Zeng Ming (2020) In Science Signaling 18(646).
Abstract

Embryo implantation involves a sterile inflammatory reaction that is required for the invasion of the blastocyst into the decidua. Adenosine triphosphate (ATP) released from stressed or injured cells acts as an important signaling molecule to regulate many key physiological events, including sterile inflammation. We found that the amount of ATP in the uterine luminal fluid of mice increased during the peri-implantation period, and this depended on the presence of an embryo. We further showed that the release of ATP from receptive epithelial cells was likely stimulated by lactate released from the blastocyst through connexin hemichannels. The ATP receptor P2y2 was present on uterine epithelial cells during the preimplantation period and... (More)

Embryo implantation involves a sterile inflammatory reaction that is required for the invasion of the blastocyst into the decidua. Adenosine triphosphate (ATP) released from stressed or injured cells acts as an important signaling molecule to regulate many key physiological events, including sterile inflammation. We found that the amount of ATP in the uterine luminal fluid of mice increased during the peri-implantation period, and this depended on the presence of an embryo. We further showed that the release of ATP from receptive epithelial cells was likely stimulated by lactate released from the blastocyst through connexin hemichannels. The ATP receptor P2y2 was present on uterine epithelial cells during the preimplantation period and increased in the stromal cells during the time at which decidualization began. Pharmacological inhibition of P2y2 compromised decidualization and implantation. ATP-P2y2 signaling stimulated the phosphorylation of Stat3 in uterine luminal epithelial cells and the expression of early growth response 1 (Egr1) and prostaglandin-endoperoxide synthase 2 (Ptgs2, also known as Cox-2), all of which are required for decidualization and/or implantation, in stromal cells. Short exposure to high concentrations of ATP promoted decidualization of primary stromal cells, but longer exposures or lower ATP concentrations did not. The expression of genes encoding ATP-degrading ectonucleotidases increased in the decidua during the peri-implantation period, suggesting that they may limit the duration of the ATP signal. Together, our results indicate that the blastocyst-induced release of ATP from uterine epithelial cells during the peri-implantation period may be important for the initiation of stromal cell decidualization.

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author
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publishing date
type
Contribution to journal
publication status
published
in
Science Signaling
volume
18
issue
646
article number
eaba3396
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85089931731
  • pmid:32843542
ISSN
1945-0877
DOI
10.1126/SCISIGNAL.ABA3396
language
English
LU publication?
no
additional info
Funding Information: This work was supported by the National Key Research and Development Program of China (2018YFC1004403) and the National Natural Science Foundation of China (31871511 and 31671563). Publisher Copyright: Copyright © 2020 The Authors, some rights reserved;
id
a123e2d9-3430-4ccb-ada4-b7e9bd043a48
date added to LUP
2024-02-28 14:58:02
date last changed
2024-04-27 13:30:07
@article{a123e2d9-3430-4ccb-ada4-b7e9bd043a48,
  abstract     = {{<p>Embryo implantation involves a sterile inflammatory reaction that is required for the invasion of the blastocyst into the decidua. Adenosine triphosphate (ATP) released from stressed or injured cells acts as an important signaling molecule to regulate many key physiological events, including sterile inflammation. We found that the amount of ATP in the uterine luminal fluid of mice increased during the peri-implantation period, and this depended on the presence of an embryo. We further showed that the release of ATP from receptive epithelial cells was likely stimulated by lactate released from the blastocyst through connexin hemichannels. The ATP receptor P2y2 was present on uterine epithelial cells during the preimplantation period and increased in the stromal cells during the time at which decidualization began. Pharmacological inhibition of P2y2 compromised decidualization and implantation. ATP-P2y2 signaling stimulated the phosphorylation of Stat3 in uterine luminal epithelial cells and the expression of early growth response 1 (Egr1) and prostaglandin-endoperoxide synthase 2 (Ptgs2, also known as Cox-2), all of which are required for decidualization and/or implantation, in stromal cells. Short exposure to high concentrations of ATP promoted decidualization of primary stromal cells, but longer exposures or lower ATP concentrations did not. The expression of genes encoding ATP-degrading ectonucleotidases increased in the decidua during the peri-implantation period, suggesting that they may limit the duration of the ATP signal. Together, our results indicate that the blastocyst-induced release of ATP from uterine epithelial cells during the peri-implantation period may be important for the initiation of stromal cell decidualization.</p>}},
  author       = {{Gu, Xiao Wei and Chen, Zi Cong and Yang, Zhen Shan and Yang, Yan and Yan, Ya Ping and Liu, Yue Fang and Pan, Ji Min and Su, Ren Wei and Yang, Zeng Ming}},
  issn         = {{1945-0877}},
  language     = {{eng}},
  number       = {{646}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Signaling}},
  title        = {{Blastocyst-induced ATP release from luminal epithelial cells initiates decidualization through the P2Y2 receptor in mice}},
  url          = {{http://dx.doi.org/10.1126/SCISIGNAL.ABA3396}},
  doi          = {{10.1126/SCISIGNAL.ABA3396}},
  volume       = {{18}},
  year         = {{2020}},
}