**2.4.5 L-Selectin ligand**

328 Endometriosis - Basic Concepts and Current Research Trends

ART procedure, clinicians can improve embryo formation considerably; however, no therapies are available to make the endometrium more receptive. Expression of various implantation markers and proteins lead to remodeling of the endometrial matrix thereby transforming the endometrium towards a receptive milieu. Several molecular repertoires expressed during the implantation window are considered to be useful markers of implantation. Expression of various markers including pinopodes αvβ3 integrin, LIF, Lselectin ligand and Mucin-1 throughout the different stages of implantation are considered

Pinopodes, also known as uterodomes, are large cytoplasmic protrusions from the endometrial epithelial surface and are several micrometers wide. These are specialized cell structures that are involved in adhesion and penetration of the blastocyst into the stroma. These structures project into the uterine lumen and are above the microvilli level. Their expression is limited to a maximum period of 2 days during the menstrual cycle corresponding to the presumed window of implantation (Stavreus-Evers et al., 2001). Endometrial pinopodes development is associated with the mid-luteal phase increased expression of leukaemia inhibitory factor (LIF) and its receptor (Aghajanova et al., 2003), progesterone (Stavreus-Evers et al., 2001) and integrin αVβ3 (Lessey et al., 1992). Advocated as a marker of uterine receptivity, their expression, has been investigated solely by means of

Integrins are surface ligands, usually glycoproteins, belonging to the class of cell adhesion molecules (CAM). An integrin molecule consists of two different, non-covalently linked α and β subunits that are paired to form various heterodimers with distinct function (Hynes, 2002). At least 20 types of integrin heterodimer have been defined, which form from 14α and 9β subunits (Lindhard 2002). Integrins are unusual cell surface receptors in that they bind with low affinity and are present in large numbers, allowing for ligand motility without loss of attachment. Endometrial epithelial cells constitutively express certain integrins, whereas others are cycle dependent (Lessey 1992). αvβ3, an example of the latter is present on the apical surface of both luminal endometrial cells and human embryos. 41 different aberrant expressions of this integrin are reported in women with endometriosis (Lessey et al., 1994).

LIF is a member of the IL-6 family and is secreted by the endometrial epithelium, CD16– CD56 natural killer cells and type 2 T-helper cells. Animal and human studies indicate that LIF plays an important role in implantation and for pregnancy to occur (Lass et al., 2001). LIF protein can be detected by immunohistochemistry in the luminal, glandular and stromal epithelium. There is very little LIF expression in proliferative endometrium, but levels increase during the secretory phase, reaching a maximum between days 19 and 25, which

Mucins are high molecular weight (MW) glycoproteins, which contain at least 50% of carbohydrate O-linked to a threonine/serine rich peptide core (Gendler et al., 1990). Among

to be responsible for endometrial receptivity.

scanning electron microscopy (SEM) (Develioglu et al., 2000).

coincides with the implantation window (Charnock-Jones 1994).

**2.4.1 Pinopodes** 

**2.4.2 Integrins** 

**2.4.3 LIF** 

**2.4.4 Mucins** 

Selectins are glycoproteins which also belong to the CAM family. The expression of selectin oligosaccharide-based ligands, such as MECA-79 or HECA-452, is up-regulated during the window of implantation (Genbacev et al., 2003). MECA-79 is immunolocalized in the luminal and glandular endometrial epithelium throughout the menstrual cycle, although the staining considerably intensifies during the mid-secretory phase. The physiological importance of the interaction between L-selectin and its oligosaccharide ligands has been investigated in the human endometrium (Genbacev et al., 2003).

Though several studies investigating endometrial receptivity during implantation window are documented, the mechanism responsible for implantation failure in endometriosis is still poorly understood. Expression of various cell adhesion molecules and pinopodes in women with endometriosis is explored in the present study. Since, COX-2 is reported to be physiologically involved in the process of angiogenesis (Matsumoto et al., 2002), and in view of the fact that angiogenesis is essential for endometrial remodeling, we were motivated to assess the expression of various angiogenic factors including VEGFR, MMP-2,-9 and their tissue inhibitors in women with endometriosis during the implantation window. Additionally, expression of COX-2 was studied to assess their associated regulatory role in the process of endometrial remodeling during implantation window.
