The Impact of Multiparity on Uterine Gene Expression and Decidualization in Mice.

It has been well established that a previous pregnancy exhibits a beneficial effect on the subsequent pregnancy. However, the underlying mechanisms have not been defined. We hypothesized that multiparity may affect decidualization process during early pregnancy. To test this hypothesis, we analyzed global gene changes associated with multiparity in the mouse uterus using RNA-sequencing (RNA-seq). We identified a total of 131 differentially expressed genes (fold change > 2 and false discovery rate < 0.05), of which 58 were downregulated and 73 genes were upregulated in the second pregnancy (SP) compared to the first pregnancy. Functional clustering analysis showed that genes involved in stress response were significantly enriched. Most importantly, a significant portion of differentially expressed genes, 14 genes or 10.7%, overlapped with the gene list associated with decidualization. Quantitative reverse transcription (RT) polymerase chain reaction (qRT-PCR) analysis confirmed a decreased expression of 4 genes (Klk1, kallikrein 1; H2-Eb1, histocompatibility 2 class II antigen E beta; Mmp7, matrix metallopeptidase 7; Pdpn, podoplanin) and an increase in expression of 2 genes (Thy1, thymus cell antigen 1; Ptgs2, prostaglandin-endoperoxide synthase 2) in SP. Beyond protein-coding genes, we also identified a differentially expressed long noncoding RNA AI506816. Our data provide new insights into the molecular mechanisms underlying the beneficial effect of multiparity.