Nobiletin-induced partial abrogation of deleterious effects of AKT inhibition on preimplantation bovine embryo development in vitro†.

Autor:	Cajas YN; Department of Animal Reproduction, National Center Institute for Agriculture and Food Research and Technology (CSIC-INIA), Madrid, Spain., Cañón-Beltrán K; Department of Animal Reproduction, National Center Institute for Agriculture and Food Research and Technology (CSIC-INIA), Madrid, Spain., Núñez-Puente C; Department of Animal Reproduction, National Center Institute for Agriculture and Food Research and Technology (CSIC-INIA), Madrid, Spain., Gutierrez-Adán A; Department of Animal Reproduction, National Center Institute for Agriculture and Food Research and Technology (CSIC-INIA), Madrid, Spain., González EM; Department of Anatomy and Embryology, Veterinary Faculty, Complutense University of Madrid (UCM), Madrid, Spain., Agirregoitia E; Department of Physiology, Faculty of Medicine and Nursing, Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU), Leioa, Spain., Rizos D; Department of Animal Reproduction, National Center Institute for Agriculture and Food Research and Technology (CSIC-INIA), Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Biology of reproduction [Biol Reprod] 2021 Dec 20; Vol. 105 (6), pp. 1427-1442.
DOI:	10.1093/biolre/ioab184
Abstrakt:	During preimplantational embryo development, PI3K/AKT regulates cell proliferation and differentiation and nobiletin modulates this pathway to promote cell survival. Therefore, we aimed to establish whether, when the AKT cascade is inhibited using inhibitors III and IV, nobiletin supplementation to in vitro culture media during the minor (2- to 8-cell stage, MNEGA) or major (8- to 16-cell stage, MJEGA) phases of EGA is able to modulate the development and quality of bovine embryos. In vitro zygotes were cultured during MNEGA or MJEGA phase in SOF + 5% FCS or supplemented with: 15 μM AKT-InhIII; 10 μM AKT-InhIV; 10 μM nobiletin; nobiletin + AKT-InhIII; nobiletin + AKT-InhIV; 0.03% DMSO. Embryo development was lower in treatments with AKT inhibitors, while combination of nobiletin with AKT inhibitors was able to recover their adverse developmental effect and also increase blastocyst cell number. The mRNA abundance of GPX1, NFE2L2, and POU5F1 was partially increased in 8- and 16-cell embryos from nobiletin with AKT inhibitors. Besides, nobiletin increased the p-rpS6 level whether or not AKT inhibitors were present. In conclusion, nobiletin promotes bovine embryo development and quality and partially recovers the adverse developmental effect of AKT inhibitors, which infers that nobiletin probably uses another signaling cascade that PI3K/AKT during early embryo development in bovine. (© The Author(s) 2021. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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