Lysophosphatidic Acid Accelerates Bovine In Vitro-Produced Blastocyst Formation through the Hippo/YAP Pathway

Int J Mol Sci. 2021 May 31;22(11):5915. doi: 10.3390/ijms22115915.

Abstract

The segregation of trophectoderm (TE) and inner cell mass in early embryos is driven primarily by the transcription factor CDX2. The signals that trigger CDX2 activation are, however, less clear. In mouse embryos, the Hippo-YAP signaling pathway is important for the activation of CDX2 expression; it is less clear whether this relationship is conserved in other mammals. Lysophosphatidic acid (LPA) has been reported to increase YAP levels by inhibiting its degradation. In this study, we cultured bovine embryos in the presence of LPA and examined changes in gene and protein expression. LPA was found to accelerate the onset of blastocyst formation on days 5 and 6, without changing the TE/inner cell mass ratio. We further observed that the expression of TAZ and TEAD4 was up-regulated, and YAP was overexpressed, in LPA-treated day 6 embryos. However, LPA-induced up-regulation of CDX2 expression was only evident in day 8 embryos. Overall, our data suggest that the Hippo signaling pathway is involved in the initiation of bovine blastocyst formation, but does not affect the cell lineage constitution of blastocysts.

Keywords: CDX2; LPA; YAP; bovine; lineage segregation; trophectoderm.

MeSH terms

  • Acyltransferases / genetics
  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Blastocyst / drug effects*
  • Blastocyst Inner Cell Mass / drug effects
  • CDX2 Transcription Factor / genetics*
  • Cattle
  • Cell Lineage / genetics
  • Embryonic Development / drug effects
  • Embryonic Development / genetics
  • Gene Expression Regulation, Developmental / drug effects
  • Hippo Signaling Pathway
  • Lysophospholipids / pharmacology*
  • Mice
  • Protein Serine-Threonine Kinases / genetics*
  • Signal Transduction / drug effects
  • Transcription Factors / genetics
  • Trophoblasts / drug effects
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • CDX2 Transcription Factor
  • Lysophospholipids
  • Transcription Factors
  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • Acyltransferases
  • tafazzin protein, mouse
  • Protein Serine-Threonine Kinases
  • lysophosphatidic acid