This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our 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. Several studies indicate 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. The extracellular matrix protein fibronectin is also dramatically up-regulated in the uppermost functionalis zones of the endometrium during late menstruation and the endometrial repair phase of the menstrual cycle. We hypothesize that fibronectin-integrin binding may play a role in regulating the inflammatory response and further have essential actions during the cessation of menstrual bleeding. 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 an Affymetrix analysis of samples of macaque endometrial RNA isolated from rhesus macaques during the menstrual phase of the cycle (cycle day 0 ?6;n=4/day). The gene chip analysis revealed that integrin- a2,-a3, -a5, b1, b3, b6, and b8 were significantly increased the menstrual phase of the cycle. We have confirmed this expression by Realtime PCR, and localization of these targets by situ hybridization is underway.
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