Progesterone withdrawal up-regulates fibronectin and integrins during menstruation and repair in the rhesus macaque endometrium

BACKGROUND: Fibronectin (FN) is a component of the extracellular matrix that participates in wound healing in various tissues as an adhesive ligand for integrins (Itgs). To determine whether these molecules play similar roles during menstrual repair, we evaluated the expression and localization of FN and specific Itgs in the primate endometrium under hormonally controlled conditions. METHODS: Ovariectomized rhesus macaques were treated for 2 weeks with estradiol (E₂) followed by E₂ with progesterone for 2 weeks. On day 28, progesterone was withdrawn and uteri were collected during menstruation, postmenstrual repair, and the proliferative and secretory phases. Analysis was by focused microarray, real time PCR, in situ hybridization and immunocytochemistry. RESULTS: Progesterone withdrawal induced significant elevations of FN, Itg α5 and Itg β1 transcripts during menstruation as compared to day 28 (FN: P < 0.01; Itg α5: P < 0.05; Itg β1: P < 0.05; real time PCR). These increases were concentrated in the glandular epithelium (FN) and stroma (Itg α5β1) of the uppermost zones. Cyclic changes in Itg α3 occurred in the glandular epithelium. CONCLUSIONS: Spatially and temporally restricted peaks of expression of FN and its Itg receptors are closely correllated with menstruation and postmenstrual repair in the primate endometrium.