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פותח על ידי קלירמאש פתרונות בע"מ -
Identification of Trophectoderm-Derived Cripto as an Essential Mediator of Embryo Implantation
Year:
2018
Source of publication :
Endocrinology
Authors :
אלבז, מיכל
;
.
גנין, אולגה
;
.
גרשון, ערן
;
.
מוצ'ניק, מורן
;
.
צינמון, יובל
;
.
קלייניאן-אלעזרי, אלונה
;
.
קרסנטי, שרון
;
.
Volume :
159
Co-Authors:

Booker, E.; Gray, P.C.

Facilitators :
From page:
1793
To page:
1807
(
Total pages:
15
)
Abstract:

Cripto-1 (TDGF1) is a multifunctional signaling factor that stimulates cellular effects, including proliferation, migration, survival, epithelial-to-mesenchymal transition, and angiogenesis, to regulate embryogenesis, tissue homeostasis, and tumorigenesis. Those cell behaviors are also associated with implantation of the embryo into the uterine wall, and this led us to investigate the role of embryo-derived Cripto in embryo attachment and implantation. In this study, we show that Cripto and its signaling mediator GRP78 are uniquely localized to embryo implantation sites. We knocked down Cripto expression specifically in trophoblast cells and found that this resulted in a corresponding decrease in the levels of its downstream signaling mediators, phosphorylated (phospho-)SMAD2, phospho-SRC, phospho'extracellular signal'regulated kinase, and phospho- AKT, which are also known mediators of embryo implantation. We then transplanted Cripto knockdown and control embryos into uteri of pseudopregnant female mice and found that embryos with Cripto-depleted trophoblast cells had dramatically impaired capacity to attach to the uterine wall when compared with controls. This loss of appropriate embryo attachment following Cripto knockdown in trophoblast cells was associated with abnormally enlarged implantation sites that were almost completely devoid of microvessels. A role for Cripto in embryo implantation was further supported by our demonstration that attachment of trophoblast-derived spheroids to endometrial cells in vitro was stimulated by Cripto treatment and diminished by treatment with either of two mechanistically distinct Cripto blocking agents. Collectively, our findings identify Cripto as a novel and critical embryo attachment factor and suggest that modulation of Cripto signaling may have significant therapeutic potential for the treatment of infertility and other related disorders. Copyright © 2018 Endocrine Society.

Note:
Related Files :
animal fertility
animal reproduction
Genetics
עוד תגיות
תוכן קשור
More details
DOI :
https://doi.org/10.1210/en.2017-03039
Article number:
0
Affiliations:

Department of Ruminant Science, Agricultural Research Organization, Hamaccabim Road 63, Rishon Letzion, Israel; Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel; Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, San Diego, CA, United States; Department of Poultry and Aquaculture Science, Agricultural Research Organization, Rishon LeZion, Israel

Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
36327
Last updated date:
02/03/2022 17:27
Creation date:
05/08/2018 09:09
Scientific Publication
Identification of Trophectoderm-Derived Cripto as an Essential Mediator of Embryo Implantation
159

Booker, E.; Gray, P.C.

Identification of Trophectoderm-Derived Cripto as an Essential Mediator of Embryo Implantation

Cripto-1 (TDGF1) is a multifunctional signaling factor that stimulates cellular effects, including proliferation, migration, survival, epithelial-to-mesenchymal transition, and angiogenesis, to regulate embryogenesis, tissue homeostasis, and tumorigenesis. Those cell behaviors are also associated with implantation of the embryo into the uterine wall, and this led us to investigate the role of embryo-derived Cripto in embryo attachment and implantation. In this study, we show that Cripto and its signaling mediator GRP78 are uniquely localized to embryo implantation sites. We knocked down Cripto expression specifically in trophoblast cells and found that this resulted in a corresponding decrease in the levels of its downstream signaling mediators, phosphorylated (phospho-)SMAD2, phospho-SRC, phospho'extracellular signal'regulated kinase, and phospho- AKT, which are also known mediators of embryo implantation. We then transplanted Cripto knockdown and control embryos into uteri of pseudopregnant female mice and found that embryos with Cripto-depleted trophoblast cells had dramatically impaired capacity to attach to the uterine wall when compared with controls. This loss of appropriate embryo attachment following Cripto knockdown in trophoblast cells was associated with abnormally enlarged implantation sites that were almost completely devoid of microvessels. A role for Cripto in embryo implantation was further supported by our demonstration that attachment of trophoblast-derived spheroids to endometrial cells in vitro was stimulated by Cripto treatment and diminished by treatment with either of two mechanistically distinct Cripto blocking agents. Collectively, our findings identify Cripto as a novel and critical embryo attachment factor and suggest that modulation of Cripto signaling may have significant therapeutic potential for the treatment of infertility and other related disorders. Copyright © 2018 Endocrine Society.

Scientific Publication
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