1. Academic Validation
  2. Nobiletin enhances the development and quality of bovine embryos in vitro during two key periods of embryonic genome activation

Nobiletin enhances the development and quality of bovine embryos in vitro during two key periods of embryonic genome activation

  • Sci Rep. 2021 Jun 3;11(1):11796. doi: 10.1038/s41598-021-91158-7.
Karina Cañón-Beltrán  # 1 2 Yulia N Cajas  # 1 Serafín Peréz-Cerezales 1 Claudia L V Leal 1 3 Ekaitz Agirregoitia 4 Alfonso Gutierrez-Adán 1 Encina M González 5 Dimitrios Rizos 6
Affiliations

Affiliations

  • 1 Department of Animal Reproduction, National Institute for Agriculture and Food Research and Technology (INIA), 28040, Madrid, Spain.
  • 2 Departamento de Ciencias Biológicas, Universidad Técnica Particular de Loja, Loja, 110107, Ecuador.
  • 3 Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, 13635-900, Brazil.
  • 4 Department of Physiology, Faculty of Medicine and Nursing, Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU), 48940, Bizkaia, Spain.
  • 5 Department of Anatomy and Embryology, Veterinary Faculty, Complutense University of Madrid (UCM), 28040, Madrid, Spain.
  • 6 Department of Animal Reproduction, National Institute for Agriculture and Food Research and Technology (INIA), 28040, Madrid, Spain. drizos@inia.es.
  • # Contributed equally.
Abstract

In vitro culture can alter the development and quality of bovine embryos. Therefore, we aimed to evaluate whether nobiletin supplementation during EGA improves embryonic development and blastocyst quality and if it affects PI3K/Akt signaling pathway. In vitro zygotes were cultured in SOF + 5% FCS (Control) or supplemented with 5, 10 or 25 µM nobiletin (Nob5, Nob10, Nob25) or with 0.03% dimethyl-sulfoxide (CDMSO) during minor (2 to 8-cell stage; MNEGA) or major (8 to 16-cell stage; MJEGA) EGA phase. Blastocyst yield on Day 8 was higher in Nob5 (42.7 ± 1.0%) and Nob10 (44.4 ± 1.3%) for MNEGA phase and in Nob10 (61.0 ± 0.8%) for MJEGA phase compared to other groups. Mitochondrial activity was higher and lipid content was reduced in blastocysts produced with nobiletin, irrespective of EGA phase. The mRNA abundance of CDK2, H3-3B, H3-3A, GPX1, NFE2L2 and PPARα transcripts was increased in 8-cells, 16-cells and blastocysts from nobiletin groups. Immunofluorescence analysis revealed immunoreactive proteins for p-AKT forms (Thr308 and Ser473) in bovine blastocysts produced with nobiletin. In conclusion, nobiletin supplementation during EGA has a positive effect on preimplantation bovine embryonic development in vitro and corroborates on the quality improvement of the produced blastocysts which could be modulated by the activation of Akt signaling pathway.

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