Neuronatin gene expression levels affect foetal growth and development by regulating glucose transport in porcine placenta

Gene. 2022 Jan 30:809:146051. doi: 10.1016/j.gene.2021.146051. Epub 2021 Oct 29.

Abstract

Imprinted genes play important regulatory roles in the growth and development of placentas and foetuses during pregnancy. In a previous study, we found that the imprinted gene Neuronatin (NNAT) is involved in foetal development; NNAT expression was significantly lower in the placentas of piglets that died neonatally compared to the placentas of surviving piglets. However, the function and mechanism of NNAT in regulating porcine placental development is still unknown. In this study, we collected the placentas of high- and low-weight foetuses at gestational day (GD 65, 90), (n = 4-5 litters/GD) to investigate the role of NNAT in regulating foetal growth and development. We found that the mRNA and protein levels of NNAT were significantly higher in the placentas of high-weight than low-weight foetuses. We then overexpressed NNAT in porcine placental trophoblast cell lines (pTr2) and demonstrated that NNAT activated the PI3K-AKT pathway, and further promoted the expression of glucose transporter 1 (GLUT1) and increased cellular calcium ion levels, which improved glucose transport in placental trophoblast cells in vitro. To conclude, our study suggests that NNAT expression impacts porcine foetal development by regulating placental glucose transport.

Keywords: Glucose transport; Imprinted gene; Neuronatin gene; Placenta.

MeSH terms

  • Animals
  • Calcium Signaling / genetics
  • Cell Line
  • Female
  • Fetal Weight / genetics
  • Gene Expression Regulation, Developmental*
  • Glucose / genetics
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism
  • Glucose Transporter Type 3 / genetics
  • Glucose Transporter Type 3 / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Placenta
  • Pregnancy
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Swine
  • Trophoblasts / metabolism
  • Trophoblasts / physiology

Substances

  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins c-akt
  • Glucose