Co-ordinated regulation of neurogenin-3 expression in the maternal and fetal pancreas during pregnancy

Acta Obstet Gynecol Scand. 2014 Nov;93(11):1190-7. doi: 10.1111/aogs.12495. Epub 2014 Sep 23.

Abstract

Objective: Several studies have shown increased beta cell mass during pregnancy in both rodents and humans. Proliferation of existing beta cells seems to be the predominant mechanism in rodents, whereas the mechanism in humans is unclear. We hypothesized that neogenesis contributes to the increased beta cell mass in pregnancy and that circulating factors are involved.

Samples: Pancreatic tissue from mice and rat and serum from pregnant women.

Method: Morphometric analysis of pancreas of pregnant and nonpregnant mice was carried out by immunocytochemical staining for the neogenic marker neurogenin-3. Messenger RNA levels of neurogenin-3 and the transcription factor musculoaponeurotic fibrosarcoma oncogene family protein B in fetal rat pancreas cells, cultured with serum from pregnant women, were measured by quantitative polymerase chain reaction.

Main outcome measures: The number of neurogenin-3-positive cells present in pregnant mice was increased compared with nonpregnant mice. Neurogenin-3 and musculoaponeurotic fibrosarcoma oncogene family protein B mRNA was detected in fetal rat pancreas exposed to serum from pregnant women.

Results: In pregnant mice we found a 3.6-fold increase in beta cell volume at day 18 compared with nonpregnant mice and a 3.5-fold increase in neurogenin-3 volume at day 14, mainly located in the acinar compartment where it was eightfold higher than in nonpregnant mice. In fetal rat pancreatic cells exposed to serum from pregnant women we found a marked increase in both neurogenin-3 and musculoaponeurotic fibrosarcoma oncogene family protein B mRNA levels in fibroblast-like cells.

Conclusion: These results suggest that neogenesis contributes to the increased beta cell mass in pregnancy and that circulating factors are involved in beta cell formation in both the maternal and fetal pancreas during pregnancy.

Keywords: Neurogenin-3; beta cells; neogenesis; pancreas; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / blood*
  • Female
  • Fetus / metabolism*
  • Humans
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • Nerve Tissue Proteins / blood*
  • Pancreas / metabolism*
  • Pregnancy
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • NEUROG3 protein, human
  • Nerve Tissue Proteins
  • Neurog3 protein, rat
  • RNA, Messenger