FIBRONECTIN-INTEGRIN BINDING & POST MENSTRUAL REPAIR IN THE MACAQUE ENDOMETRIUM

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal is to better understand normal menstruation and menstrual disorders including menorrhagia and breakthrough bleeding. Menstruation is a cyclical process of endometrial destruction and regeneration, initiated by an acute withdrawal of progesterone (P) at the end of the menstrual cycle. This study has two specific aims: Aim 1 is to characterize the pattern of fibronectin, integrin and inflammatory chemokine receptor expression in the macaque endometrium during menses. Aim 2 is to determine the effect of fibronectin-integrin blockade on the regulation of genes associated with menstruation and endometrial repair. We have now completed a gene array of samples of macaque endometrial RNA isolated from rhesus macaques during the menstrual phase of the cycle (cycle day 0 [unreadable]6;n=4/day). Our results support the view that in addition to fibronectin and the fibronectin receptor, several mediators of inflammation are strikingly up regulated in the endometrium preceding menstruation. This supports previous studies indicating that P withdrawal triggers an inflammation-like response that includes up-regulation of interleukin-8 (IL 8) and monocyte chemotactic protein-1 (MCP 1) that can stimulate the recruitment of neutrophils, monocytes and macrophages during menses.