Abstract |
The formation of the corpus luteum (CL) is critical for the establishment of a
successful pregnancy. Following ovulation, under the influence of luteogenic
hormones, the CL develops from the remnants of the ovulated ovarian follicle. This
process involves intense reorganization of constituent cells, phenomena that includes
varying cell-matrix interactions. These events, however, are poorly characterized.
Adhesion molecules, especially integrins, have crucial role in the physiological
functions of many different systems. Many studies, in the past, have established for
several cell types that the binding of cell surface integrins to their ligands in the
extracellular matrix facilitates cell proliferation, migration and survival. Integrins have
also been found to participate in many important functions of the reproductive system,
such as fertilization, interactions between the preimplantation embryo and endometriun
as well as trophoblast outgrowth during implantation. Moreover, it has been
demonstrated that activity of integrins was regulated by human chorionic gonadotropin
(hCG) and vascular endothelial growth factor (VEGF).
In order to understand the role and potential regulation of cell-matrix
interactions in the formation of the CL, we investigated the expression of the matrix
protein fibronectin (FN) and selected FN-binding integrin receptors on luteinized
granulosa cells (GCs). We further examined the possible regulation of that expression
by the luteogenic hormone, hCG and the involvement of mitogenic VEGF. Lastly, we
investigated the role of the aforementioned integrins in promoting the adhesion,
migration and survival of GCs.
The present data reported that FN is detected around GCs with luteinization,
while several FN-binding integrins, along with the VEGF receptor (Flt-1), appeared on
the surface of these cells during the early luteal phase. Expression of these proteins
declined in the late luteal phase with regression of the CL. In vitro, GCs released FN
and stimulation of these cells with hCG, increased the surface expression of α5β1 and
αvβ3 integrins, as well as the amount of FN associated with the cell surface. These
effects were reproduced by stimulation with VEGF and hCG-stimulated up-regulation
of FN, α5β1 and αvβ3 on the surface of GCs was inhibited by anti-VEGF antibody. In
addition, there has been shown that expression of α5β1 and αvβ3 integrins mediates
adhesion to FN, an ability that promotes cell movement and prevents apoptosis.
In conclusion, the present study reports new data on the role of integrins in
migration, adhesion and apoptosis of human GCs, and the regulation of these processes
by the hCG and VEGF, and thus indicate the potential contribution of these molecules
in formation and maintenance of the CL.
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