Biphasic Changes in β-Cell Mass Around Parturition Accompanied by Increased Serotonin Production

Abstract

Pancreatic β-cell mass is known to be considerably altered during pregnancy and after parturition in rodents and humans. Although βcell mass is increased during pregnancy and starts to return toward its original level shortly after parturition, the cellular mechanisms by which β-cell mass during this period is regulated remains unclear. To address this issue in mice, we quantified β-cell mass and investigated the mechanisms underlying its regulation throughout the perinatal and postpartum period. The increased β-cell size and proliferation during pregnancy were significantly reduced shortly after parturition, whereas there was no evidence of β-cell reprogramming or increased apoptosis. Direct RNA sequencing of islets from pregnant and postpartum mice demonstrated dynamic changes in gene expression patterns, showing robust down-regulation of cell cycle-related genes 1 day after parturition, and the biphasic up-regulation of serotonin metabolism-related genes during pregnancy and at postpartum day 7. Serotonin synthesis was activated during lactation in human as well as in mice. Taken together, these findings demonstrate that β-cell mass is decreased shortly after parturition owing to reduced β-cell size and proliferation, and is subsequently increased, in association with lactation and serotonin biosynthesis. Funding Statement: This work was supported by research grant for Cross-disciplinary Collaboration, Juntendo University 2017 (29-35). Declaration of Interests: The authors stated: There is no conflict of interest on this study. Ethics Approval Statement: The study design was approved by the ethics committee of the Hirosaki University School of Medicine (approval number 2014-269), and the study conforms to the provision of the Declaration of Helsinki.