Female Reproductive Tract

Gene Expression Profiling of Neonatal Mouse Uterine Development

Abstract
Postnatal uterine development involves differentiation and development of the endometrial glandular epithelium from the luminal epithelium as well as development of the mesenchyme into the endometrial stroma and myometrium. This period of development is critical, because exposure of neonates to endocrine disruptors compromises reproductive cycles and pregnancy in the adult. However, the hormonal, cellular and molecular mechanisms regulating postnatal uterine development remain largely unknown. In order to identify candidate genes and gene networks that regulate postnatal uterine development, uteri were collected from CD-1 outbred mice on postnatal days (PND) 3, 6, 9, 12 and 15, and gene expression profiling was conducted using Affymetrix mouse genome U74Av2 GeneChips in Study One. Of the approximately 12,000 genes analyzed, 9,002 genes were expressed in the uterus, and expression of 3,012 genes increased or decreased 2-fold during uterine development. In Study Two, the uterine epithelium was enzymatically separated from the stroma/myometrium on PNDs 3, 6 and 9, and gene expression profiling was conducted using CodeLink UniSet Mouse I Expression Bioarrays. Results from these two studies support the hypothesis that postnatal uterine development is a complex process involving overlapping positive and negative changes in uterine epithelial and stromal/myometrial gene expression. Candidate genes regulating uterine development encode secreted factors (Wnt5a, Wnt7a,), transcription factors (Hoxa10, Hoxa11, Hoxd10, MSX-1), enzymes (matrix metalloproteinases, cathepsin, carbonic anhydrase), growth factors (IGF-II, IGF binding proteins), and components of the extracellular matrix (osteopontin) to name a few. The candidate genes and gene networks identified by transcriptional profiling provides an important foundation to discern and understand mechanisms regulating postnatal uterine morphogenesis.

Key words: Female Reproductive Tract • Developmental biology • Gene regulation • Uterus

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