Uterus and endometrium: Immunohistochemical localization of extracellular matrix proteins in luteal phase endometrium of fertile and infertile patients

Abstract

The lack of expression of certain components involved in cell adhesion and migration is believed to contribute to endometrial dysfunction and implantation failure. The purpose of this study was to investigate whether luteal phase endometrium in women with unexplained infertility differs, with respect to specific extracellular matrix (ECM) proteins, from endometrium of normal fertile women. A panel of monoclonal antibodies to collagen type IV, fibronectin and laminin was used to characterize the localization of ECM components in the different endometrial compartments. Precisely timed endometrial biopsies obtained at 4, 7, 10 and 13 days following the luteinizing hormone surge were obtained from 22 normal fertile women (group 1) and 24 women suffering from unexplained infertility (group 2). Paraffin-embedded sections were labelled using the streptavidin-biotin alkaline phosphatase technique. In group 1, collagen type IV, fibronectin and laminin were absent from the luminal epithelium but present in stromal cells and the basement membrane of glands and blood vessels. In group 2, these components were absent from all endometrial regions using equivalent titres of antibody to those used in group 1. This suggests that the endometrium of women with unexplained infertility demonstrates defects in the distribution of certain ECM glycoproteins. A possible consequence of this defect may be implantation failure.

2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

“…Remodeling of the endometrial extracellular matrix, mediated by an altered balance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), is indispensable for successful implantation and placentation, and has been well described in humans and rodents (Farrar and Carson, 1992;Clark et al, 1993;Das et al, 1997;Hurst and Palmay, 1999). Defects in the distribution of certain ECM glycoproteins have been implicated in implantation failure in women suffering from unexplained infertility (Bilalis et al, 1996) and functional studies using MMP inhibitors…”

Autocrine/paracrine regulation of human endometrial stromal remodeling by laminin and type IV collagen

“…These ECM components were also reported to regulate trophoblast proliferation and differentiation during pregnancy (7)(8)(9)(10). Furthermore, abnormal expression of these ECM components in the endometrium was reported in a patient, infertile from an unknown cause (1).…”

“…Therefore, remodeling of the functional human endometrium must involve the cyclic production of extracellular matrix (ECM) that occupies the intercellular spaces in addition to cell regeneration and proliferation. Laminin and type IV collagen (COL-4) are well-known major components of epithelial basement membranes in the human body, and have been reported to localize in the basement membrane structure of human endometrial epithelium (1,2). Several studies have shown that these ECM components are produced at a high level in human deciduas (3,4), while laminin was reported to inhibit endometrial stromal decidualization (5,6).…”

Remodeling of the human endometrial epithelium is regulated by laminin and type IV collagen

“…Laminin has been reported to inhibit endometrial stromal differentiation (6,7), while both laminin and COL-4 have been found to regulate trophoblast proliferation and differentiation during pregnancy (8)(9)(10)(11). Furthermore, abnormal expression of these ECM components in the endometrium was reported in a patient with unexplained infertility (1). We recently demonstrated that laminin and COL-4 regulated normal human endometrial stromal remodeling in an autocrine/paracrine fashion during the menstrual cycle (5).…”

“…Remodeling of the functional human endometrium must involve cyclic production of extracellular matrix (ECM), as well as cell regeneration and proliferation. Laminin and type IV collagen (COL-4) are well-known major components of epithelial basement membranes in the human body and have been reported to localize in the basement membrane-like structures (BM-like-S) of human endometrial epithelium (1,2). Several studies have shown that both these ECM components are highly expressed in human endometrial stromal cells and deciduas (3)(4)(5).…”