Naringenin-induced migration of embrynoic trophectoderm cells is mediated via PI3K/AKT and ERK1/2 MAPK signaling cascades

Whasun Lim, Gwonhwa Song

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


For successful pregnancy, a well-coordinated network of growth factors, nutrients and hormones is required for fetal-maternal interactions. Naringenin, as a weak phytoestrogen, improves diabetes, inflammation, neuronal diseases, cardiovascular diseases and cancers. However, the role of naringenin in migration mechanism(s) of peri-implantation conceptuses is unknown. Therefore, in the present study, we determined the effects of naringenin on migration of porcine trophectoderm (pTr) cells, which is a known in vitro model for research on trophectoderm cell biology and placental-fetal developmental biology, in order to assess intracellular signal transduction pathways activated by naringenin. Migration of pTr cells increased in a dose-dependent manner in response to naringenin. Also, naringenin activated the phosphorylation of AKT and ERK1/2 proteins in a dose-dependent manner and those proteins were abundant mainly in the cytoplasm of naringenin-treated pTr cells. Within 30 min after treatment with 20 μM naringenin, the abundance of phosphorylated EKR1/2, P70S6K, P90RSK and S6K proteins increased, and then returned to basal levels by 120 min whereas the abundance of AKT increased gradually to 120 min post-treatment. However, the phosphorylation of AKT, P70S6K, P90RSK and S6K was reduced in naringenin-induced pTr cells pre-treated with a PI3K inhibitor (LY294002). Also, a MEK1/2 inhibitor (U0126) significantly decreased naringenin-induced phosphorylation of ERK1/2, P70S6K and S6K proteins in pTr cells. Moreover, the naringenin-stimulated migration of pTr cells was suppressed by LY294002 and U0126. Collectively, results of the present study suggest that naringenin supports migration of pTr cells through PI3K/AKT and ERK1/2 MAPK signaling pathways crucial for orchestrating conceptus-uterine interactions.

Original languageEnglish
Pages (from-to)28-37
Number of pages10
JournalMolecular and Cellular Endocrinology
Publication statusPublished - 2016 Jun 15

Bibliographical note

Funding Information:
We really appreciate Dr. Fuller W. Bazer (Texas A&M University, USA) for providing porcine trophectoderm cells for this study and for thoughtful editing and comments on our paper. This research was supported by IPET ( Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries ) ( 114065031SB020 ), Ministry of Agriculture, Food and Rural Affairs (MAFRA) , Ministry of Oceans and Fisheries (MOF) , Rural Development Administration (RDA) and Korea Forest Service (KFS) .

Publisher Copyright:
© 2016 Elsevier Ireland Ltd.


  • Migration
  • Naringenin
  • Peri-implantation
  • Trophectoderm cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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