Show simple item record  

dc.contributor.authorNajafzadeh, V.en_NZ
dc.contributor.authorHenderson, H.en_NZ
dc.contributor.authorMartinus, Ryan Dennisen_NZ
dc.contributor.authorOback, Bjornen_NZ
dc.date.accessioned2019-01-30T23:14:54Z
dc.date.available2018en_NZ
dc.date.available2019-01-30T23:14:54Z
dc.date.issued2018en_NZ
dc.identifier.citationNajafzadeh, V., Henderson, H., Martinus, R. D., & Oback, B. (2018). Bovine blastocyst development depends on threonine catabolism. bioRxiv. https://doi.org/10.1101/397562en
dc.identifier.urihttps://hdl.handle.net/10289/12307
dc.description.abstractIncreasing evidence suggests that pluripotency is a metabolically specialised state. In mouse, inner cell mass (ICM) cells and ICM-derived pluripotent stem cells (PSCs) critically depend on catabolising the amino acid threonine, while human PSCs require leucine, lysine, methionine and tryptophan. However, little is known about the specific amino acid requirements of putative pluripotent cells in bovine. We selectively depleted candidate essential amino acids (EAAs) from individually cultured bovine embryos to study their role in blastocyst development. Depleting one (-T, -M), two (-MT, -CM, -CT, -IL, -IK, -KL) or three (-CMT, -IKL) EAAs from chemically defined protein-free culture medium did not affect the morula-to-blastocyst transition from day five (D5) to D8 in vitro. By contrast, removing six (-CIKLMT, -FHRYVW), nine (+CMT, +IKL), eleven EAAs (+T, +M) or all twelve EAAs increasingly impaired blastocyst development. As no clear candidate emerged from this targeted screen, we focussed on threonine dehydrogenase (TDH), which catalyses threonine catabolism. TDH mRNA and protein was present at similar levels in trophectoderm (TE) and ICM but absent from several adult somatic tissues. We then treated morulae with an inhibitor (Qc1) that blocks TDH from catabolising threonine. Continuous exposure to Qc1 reduced total and high-quality blastocyst development from 37% to 26% and 18% to 8%, respectively (P<0.005). This was accompanied by ~2-fold decrease in ICM, TE and total cell numbers (P<0.005), which was due to increased autophagy (P<0.05). At the same time, ICM- (NANOG) and TE-restricted (KRT8) genes were up- and down-regulated, respectively (P<0.05). In summary, bovine blastocyst viability depended on TDH-mediated threonine catabolism. However, ICM and TE cells did not metabolically differ in this regard, highlighting species-specific connections between metabolism and pluripotency regulation in mouse vs cattle.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherCold Spring Harbor Laboratoryen_NZ
dc.relation.urihttps://www.biorxiv.org/content/early/2018/09/07/397562en_NZ
dc.rightsThe copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
dc.titleBovine blastocyst development depends on threonine catabolismen_NZ
dc.typeJournal Article
dc.identifier.doi10.1101/397562en_NZ
dc.relation.isPartOfbioRxiven_NZ
pubs.elements-id226672


Files in this item

This item appears in the following Collection(s)

Show simple item record