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Mechanics of mouse blastocyst hatching revealed by a hydrogel-based microdeformation assay.

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cam.issuedOnline2018-09-19
dc.contributor.authorLeonavicius, Karolis
dc.contributor.authorRoyer, Christophe
dc.contributor.authorPreece, Chris
dc.contributor.authorDavies, Benjamin
dc.contributor.authorBiggins, John S
dc.contributor.authorSrinivas, Shankar
dc.contributor.orcidBiggins, John [0000-0002-7452-2421]
dc.date.accessioned2018-11-21T00:31:41Z
dc.date.available2018-11-21T00:31:41Z
dc.date.issued2018-10-09
dc.description.abstractMammalian embryos are surrounded by an acellular shell, the zona pellucida. Hatching out of the zona is crucial for implantation and continued development of the embryo. Clinically, problems in hatching can contribute to failure in assisted reproductive intervention. Although hatching is fundamentally a mechanical process, due to limitations in methodology most studies focus on its biochemical properties. To understand the role of mechanical forces in hatching, we developed a hydrogel deformation-based method and analytical approach for measuring pressure in cyst-like tissues. Using this approach, we found that, in cultured blastocysts, pressure increased linearly, with intermittent falls. Inhibition of Na/K-ATPase led to a dosage-dependent reduction in blastocyst cavity pressure, consistent with its requirement for cavity formation. Reducing blastocyst pressure reduced the probability of hatching, highlighting the importance of mechanical forces in hatching. These measurements allowed us to infer details of microphysiology such as osmolarity, ion and water transport kinetics across the trophectoderm, and zona stiffness, allowing us to model the embryo as a thin-shell pressure vessel. We applied this technique to test whether cryopreservation, a process commonly used in assisted reproductive technology (ART), leads to alteration of the embryo and found that thawed embryos generated significantly lower pressure than fresh embryos, a previously unknown effect of cryopreservation. We show that reduced pressure is linked to delayed hatching. Our approach can be used to optimize in vitro fertilization (IVF) using precise measurement of embryo microphysiology. It is also applicable to other biological systems involving cavity formation, providing an approach for measuring forces in diverse contexts.
dc.description.sponsorshipThis work was supported by a studentship (to K.L.) from the Biotechnology and Biological Sciences Research Council (BB/ J014427/1), Lithuanian Science Council Postdoctoral Award (code 09.3.3- LMT-K-712-02-0067), the Welcome Trust (203141/Z/16/Z), and a Wellcome Senior Investigator Award (103788/Z/14/Z) (to S.S.).
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.32907
dc.identifier.eissn1091-6490
dc.identifier.issn0027-8424
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285550
dc.languageeng
dc.language.isoeng
dc.publisherProceedings of the National Academy of Sciences
dc.publisher.urlhttp://dx.doi.org/10.1073/pnas.1719930115
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectembryo cryopreservation
dc.subjecthydrogel deformation
dc.subjectmammalian embryo hatching
dc.subjectmouse blastocyst
dc.subjectpressure measurement
dc.subjectAnimals
dc.subjectBlastocyst
dc.subjectCells, Cultured
dc.subjectCryopreservation
dc.subjectEmbryo Transfer
dc.subjectEmbryo, Mammalian
dc.subjectEmbryonic Development
dc.subjectFemale
dc.subjectFertilization in Vitro
dc.subjectHydrogels
dc.subjectMice
dc.subjectPregnancy
dc.subjectZona Pellucida
dc.titleMechanics of mouse blastocyst hatching revealed by a hydrogel-based microdeformation assay.
dc.typeArticle
dcterms.dateAccepted2018-08-15
prism.endingPage10380
prism.issueIdentifier41
prism.publicationDate2018
prism.publicationNameProc Natl Acad Sci U S A
prism.startingPage10375
prism.volume115
rioxxterms.licenseref.startdate2018-10
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1073/pnas.1719930115

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