Growth factors and growth modulators in human uterine endometrium: their potential relevance to reproductive medicine.

OBJECTIVE To provide an up-to-date, comprehensive review on the presence and regulation of growth factors (GFs), GF receptors, and GF regulatory proteins in human endometrium in an effort to understand the potential roles of these proteins in endometrial cell mitosis and differentiation and in endometrial-trophoblast interactions. DESIGN Relevant studies were identified through a computerized bibliographic search (MEDLINE; BRS Information Technologies, a division of Maxwell Online, Inc., McLean, VA) and through manual scanning of recent relevant journals. RESULTS Several GFs, their receptors, and regulatory proteins have been identified in endometrium, and cellular localization and steroid-dependence of these proteins as well as action of several growth modulators on endometrial cell function have been studied. Epidermal growth factor, transforming growth factor (TGF)-alpha, platelet-derived growth factor, insulin-like growth factors (IGFs) and their binding proteins, fibroblast growth factor (FGF), TGF-beta, colony-stimulating factor (CSF)-1, and interferon-gamma regulate mitosis of endometrial cellular components in vitro. Endothelin-1 may participate in vasoconstriction and FGF may participate in angiogenesis in this tissue in vivo. Interleukins-1 and -6 are believed to be involved in endometrial T-cell activation, and TGF-beta, CSF-1, the interleukins, and the IGFs likely mediate endometrial-trophoblast interactions. The role of tumor necrosis factor in endometrium remains uncertain. CONCLUSIONS Current evidence supports the thesis that GFs play a central role in cyclic mitosis and differentiation of endometrial cellular components, recruitment of macrophages in decidualizing endometrium, endometrial-trophoblast interactions, early pregnancy maintenance, tissue shedding in the absence of implantation, and endometrial functionalis regeneration.