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Nihar Nayak1 , Ov Slayden1 *, Suzanne Lindsey1 *, Andreas Menrad2 , Kristof Chwalisz2 , Robert M Brenner1 *
Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton OR 1
Schering AG, Germany 2
Little is known concerning regulation and localization of VEGF receptors (KDR, FLT1) in primate endometrium. We used northern analysis, in situ hybridization and immunocytochemistry (ICC) with monoclonal antibodies to evaluate KDR and FLT1 expression in macaque endometrium. Uteri were obtained from ovariectomized rhesus and pigtail macaques on days 1, 2, 3, 4, 5, 6, 8, 10, 14, 21 and 28 of artificial menstrual cycles. Around the time of menses there was a strong wave of staining for KDR that was restricted to the stromal fibroblasts in the upper third of the endometrium, and a strong wave of staining for FLT1 on the basolateral surfaces of gland cells in the same zone. This unexpected stromal KDR and glandular FLT1 staining diminished by day 6-8 and was not evident later in the cycle. Northern analysis of endometrial homogenates showed a peak of KDR mRNA expression on day 2. Preliminary in situ hybridization of day 2 samples showed a strong KDR mRNA signal in the upper endometrial zones, paralleling the ICC staining for KDR. KDR and FLT1 staining was also evident on vascular elements in all endometrial zones but changed little during the cycle. The expression of KDR and FLT1 on stromal and gland cells during menstrual breakdown in the primate endometrium suggests a novel role for VEGF in this process. Matrix metalloproteinases (MMPs) are expressed by the same stromal fibroblasts and glands in the upper zones of the endometrium around the time of menstruation, and VEGF is known to increase MMP expression in some cell types. Therefore, in the primate endometrium, VEGF may act transiently through KDR and FLT-1 in stromal and glandular cells to modulate MMP expression and facilitate menstrual breakdown.
This abstract is being presented on Tuesday, August 3 at 5:00 PM at Todd 130.