Embryonic Modulation of Basic Fibroblast Growth Factor in the Rat Uterus1

Abstract
Cellular proliferation and differentiation are critical components of uterine remodeling prior to embryonic implantation. Recent studies have shown that the ovarian hormones, estrogen and progesterone, modulate these cellular events through the production of growth factors. Basic fibroblast growth factor (bFGF) has been implicated in the control of cell proliferation, differentiation, and embryonic development. To clarify its role in uterine remodeling, the cellular distribution of bFGF was examined immunohistochemically in the rat uterus during early pregnancy (Days 2-6). Basic FGF localized intracellularly in stromal and epithelial cells and within the extracellular matrix at Days 2 and 3. It was distinctly evident at the apical surface of epithelial cells at Days 4 and 5 of pregnancy. Concurrent with this apical localization, bFGF was present in the uterine luminal fluid, suggesting release of this growth factor from epithelial cells. Embryonic implantation was accompanied by increased intracellular bFGF content in luminal epithelial and decidual cells. However, similar cells outside of the implantation site and in the artificially decidualized uterus did not express analogous bFGF levels, indicating that a unique signal from the embryo triggers bFGF expression. Changes in the cell-specific distribution of bFGF imply a multifunctional role for this growth factor in uterine cell proliferation, differentiation, and embryonic implantation. In addition, the apical release of bFGF from epithelial cells indicates utilization of a novel secretory pathway for bFGF export during early pregnancy.