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

TY - JOUR

T1 - Co-ordinated regulation of neurogenin-3 expression in the maternal and fetal pancreas during pregnancy

AU - Søstrup, Birgitte

AU - Gaarn, Louise W

AU - Nalla, Amarnadh

AU - Billestrup, Nils

AU - Nielsen, Jens H

N1 - © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - 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.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.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.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.

AB - 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.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.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.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.

KW - Animals

KW - Basic Helix-Loop-Helix Transcription Factors

KW - Female

KW - Fetus

KW - Humans

KW - Insulin-Secreting Cells

KW - Mice

KW - Nerve Tissue Proteins

KW - Pancreas

KW - Pregnancy

KW - RNA, Messenger

KW - Rats

KW - Reverse Transcriptase Polymerase Chain Reaction

U2 - 10.1111/aogs.12495

DO - 10.1111/aogs.12495

M3 - Journal article

C2 - 25179808

SN - 0001-6349

VL - 93

SP - 1190

EP - 1197

JO - Acta Obstetricia et Gynecologica Scandinavica

JF - Acta Obstetricia et Gynecologica Scandinavica

IS - 11

ER -