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De-tensioning of collagen fibers optimizes endometrial receptivity and improves the rate of embryo implantation

Eldar Zehorai, Tamar Gross, Elee Shimshoni, Ron Hadas, Idan Adir, Ofra Golani, Guillaume Molodij, Ram Eitan, Karl E. Kadler, View ORCID ProfileMichal Neeman, Nava Dekel, Inna Solomonov, Irit Sagi
doi: https://doi.org/10.1101/2022.01.18.476712
Eldar Zehorai
1Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
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Tamar Gross
1Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
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Elee Shimshoni
1Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
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Ron Hadas
1Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
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Idan Adir
1Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
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Ofra Golani
2Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 76100, Israel
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Guillaume Molodij
2Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 76100, Israel
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Ram Eitan
3Gynecologic Oncology Division, Helen Schneider Hospital for Women, Rabin Medical Center; Petah-Tikva and The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Karl E. Kadler
4Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Oxford Road, Manchester M13 9PT United Kingdom
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Michal Neeman
1Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
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  • ORCID record for Michal Neeman
Nava Dekel
1Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
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Inna Solomonov
1Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
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  • For correspondence: inna.solomonov@weizmann.ac.il irit.sagi@weizmann.ac.il
Irit Sagi
1Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
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  • For correspondence: inna.solomonov@weizmann.ac.il irit.sagi@weizmann.ac.il
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Abstract

Successful embryo implantation is associated with intensive endometrium matrix remodeling, in which fibrillar collagens and matrix metalloproteinases play a key role. Here we report that topical treatment with a single dose of human collagenase-1 improves the rate of embryo implantation in murine models regardless of genetic background. Collagenase-1 treatment reduces endometrial collagen-fiber tension affecting their aligned configuration while preserving the overall integrity of the uterine tissue. The collagenase treatment causes enhanced local vascular permeability and creates an inflammatory-like environment, all of which are necessary for successful embryo implantation. We show that this specific treatment rescued heat stress and embryo transfer induced embryo failure in mice. Our findings highlight the clinical feasibility to improve endometrial receptivity for embryo implantation. This treatment approach may be used to improve livestock breeding and for assisted human reproduction medical treatments.

Teaser Mild specific collagen remodeling improves endometrial receptivity for natural and embryo- transfer-derived embryo implantation.

Competing Interest Statement

The authors have declared no competing interest.

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Posted January 18, 2022.
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De-tensioning of collagen fibers optimizes endometrial receptivity and improves the rate of embryo implantation
Eldar Zehorai, Tamar Gross, Elee Shimshoni, Ron Hadas, Idan Adir, Ofra Golani, Guillaume Molodij, Ram Eitan, Karl E. Kadler, Michal Neeman, Nava Dekel, Inna Solomonov, Irit Sagi
bioRxiv 2022.01.18.476712; doi: https://doi.org/10.1101/2022.01.18.476712
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De-tensioning of collagen fibers optimizes endometrial receptivity and improves the rate of embryo implantation
Eldar Zehorai, Tamar Gross, Elee Shimshoni, Ron Hadas, Idan Adir, Ofra Golani, Guillaume Molodij, Ram Eitan, Karl E. Kadler, Michal Neeman, Nava Dekel, Inna Solomonov, Irit Sagi
bioRxiv 2022.01.18.476712; doi: https://doi.org/10.1101/2022.01.18.476712

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