Biphasic changes in β-cell mass around parturition are accompanied by increased serotonin production

Pancreatic beta-cell mass is known to be considerably altered during pregnancy and after parturition in rodents and humans. While beta-cell mass increases during pregnancy and starts to return toward its original level after parturition, the cellular mechanisms by which beta-cell mass during this period is regulated remains unclear. To address this issue in mice, we quantified beta-cell mass and investigated the mechanisms underlying its regulation throughout the perinatal and postpartum period. The increased beta-cell size and proliferation during pregnancy were significantly reduced shortly after parturition, whereas there was no evidence of beta-cell reprogramming or increased apoptosis. Direct RNA sequencing of islets from pregnant and postpartum mice demonstrated dynamic changes in gene expression patterns, showing robust downregulation of cell cycle-related genes 1 day after parturition, and the reupregulation of serotonin metabolism-related genes at postpartum day 7. Serotonin synthesis was activated only in lactating females, accompanied by increased beta-cell mass. Taken together, these findings demonstrate that beta-cell mass is decreased shortly after parturition owing to reduced beta-cell size and proliferation, and is subsequently increased, in association with lactation and serotonin biosynthesis.