Gene Expression Profiling of Rat Uterus at Different Stages of Parturition

A fuller understanding of the process of parturition is needed in view of the current lack of efficient treatment for preterm labor. Using DNA microarrays, we have analyzed patterns of uterine gene expression at d 0 and 20 of pregnancy, at term in labor or not in labor, and at 1 d post partum. Of the 8740 genes analyzed, 562 genes undergoing significant changes were grouped into 5 distinct clusters, each containing many genes not previously known to be involved with uterine functions. Cluster 1 genes were up-regulated at labor and encompassed immune defense and immediate early response genes, including transcription factors NGFI-B/nurr77 and estrogen-responsive gene 1. Cluster 3 genes were acutely suppressed at labor and included extracellular matrix products and genes related to hormonal signaling, implying novel intrauterine mechanisms regulating intracellular cyclic GMP and local steroid hormone concentrations. At labor, more genes were suppressed than activated, indicating that, for the process of labor induction, gene suppression is at least equally important as the more extensively studied processes of gene activation. The study also points to the existence of novel uterine signaling pathways, including Wnt/frizzled and receptor activator of nuclear factor-kappaB (RANK) and its ligand, as well as the involvement of novel signaling molecules such as estrogen-responsive gene 1, decay-accelerating factor 1, and ebnerin. The present results provide the basis for further studies that will enlarge our knowledge of the mechanisms underlying labor and parturition under physiological and pathophysiological conditions.