Characterisation of osteopontin and CD44 in endometrium of infertile women.

Cell adhesion proteins osteopontin, CD44 and integrin alphaVbeta3 interact to form an adhesion complex between the embryo and endometrial surface forming an attachment that can lead to implantation. Whilst receptivity has been investigated extensively, the expression of this adhesion complex has yet to be studied simultaneously in the endometrium. This thesis establishes the expression of the adhesion complex in fertile and infertile endometrium. In addition the regulation of the adhesion complex components by distinct signalling pathways and the key regulators estrogen receptor, nuclear factor kappa B and signal transducer and activator of transcription 1 have been investigated in endometrial cell lines. Objectives: To establish the expression profile of adhesion complex components in samples obtained from fertile and infertile women. To model in vitro hormonal regulation of adhesion complex components to mimic estrogen and progesterone stimulus in the menstrual cycle. To determine if adverse environments common to poly cystic ovarian syndrome and endometriosis affect uterine expression of the adhesion complex via high glucose and pro-inflammatory cytokines. To investigate the direct regulation of Osteopontin and CD44 by estrogen and cytokine signalling through estrogen receptor ?, nuclear factor kappa B and signal transducer and activator of transcription 1. Methodology: Investigation of human biopsies and cell line models by immunohistochemistry, quantitative polymerase chain reaction, chromatin immunoprecipitation and enzyme linked immunosorbent assay. Conclusions: Adverse uterine environments including high glucose and pro-inflammatory cytokines may regulate the expression of the adhesion complex, and contribute to a lack of endometrial receptivity in endometriosis and poly cystic ovarian patients. CD44, ITGAV and ITGB3 levels may be used as markers for loss of receptivity in unexplained infertility