Female Reproductive Tract

The Estrogen Early Response Gene, FOS, Is Altered in a Baboon Model of Endometriosis

Abstract
Endometriosis, the presence of a functional endometrium outside of the uterine cavity, is associated with infertility. In our simulated model of pregnancy in baboons with experimental endometriosis, hCG infusion fails to induce expression of the immunoregulatory protein, glycodelin. To test the hypothesis that the development of endometriosis is associated with an aberrant endometrial immunological environment we examined the expression of a series of immunoregulatory genes in endometrium from baboons with and without endometriosis. Six months following intra-peritoneal inoculation with menstrual endometrium eutopic endometrium was surgically collected between days 9-11 post-ovulation. Control endometrium was similarly collected from disease free animals. Total RNA was extracted and biotinylated cDNA probes were hybridized to the SuperArray GEArray Q Series Th1/Th2/Th3 cDNA array, representing 96 genes. Gene expression levels were determined using ScanAlyze and GEArray Analyzer software. Seven genes were up-regulated, including JUND, FOS, CCL11, and NFKB1, in the endometrium from baboons with endometriosis compared to endometrium from disease free animals; one gene, IL1R1, was down-regulated. Quantitative real time PCR confirmed up-regulation of FOS and CCL11 in endometriotic eutopic endometrium. Immunohistochemical analysis revealed altered levels and distribution of FOS protein in the eutopic endometrium of baboons with induced endometriosis. These data suggest that in an induced model of endometriosis, an aberrant eutopic immunological environment results in a decreased apoptotic potential and rapid alterations in endometrial gene expression. We, therefore, propose that the reduced fecundity associated with endometriosis has a multifold etiology both in spontaneous and induced disease.

Key words: Immunology • Cytokines • Gene regulation • Steroid hormone receptors • Uterus

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