Expression of aminopeptidase N in human endometrium and regulation of its activity by estrogen.

OBJECTIVES: To determine whether aminopeptidase N (APN) regulates the cycle-dependent bioavailability of interleukin-8 (IL-8) in the endometrium. DESIGN: Prospective study. SETTING: University medical center. PATIENT(S): Women without endometrial pathology from the proliferative (n = 25) or secretory (n = 18) phase of the menstrual cycle. INTERVENTION(S): We first immunolocalized APN in the endometrium using an anti-APN antibody. We then determined the regulation of APN kinetic activity by sex steroids in endometrial stromal cell cultures. MAIN OUTCOME MEASURE(S): Expression of APN in human endometrium throughout the menstrual cycle. Regulation of APN activity by estradiol and progesterone in cultured endometrial stromal cells. RESULT(S): Immunohistochemistry of endometrial sections revealed staining of endometrial stroma throughout the menstrual cycle. There was no detectable staining in glandular cells. The expression of APN as detected by immunohistochemistry was significantly lower in the early proliferative phase. In cultured cells, estradiol inhibited APN activity in a concentration-dependent manner. Progesterone did not have a significant effect. CONCLUSION(S): Stromal localization of APN in endometrium may explain the epithelial rather than stromal presence of IL-8 in vivo. Decreased expression of APN may increase IL-8 bioavailability thus contributing to angiogenesis and polymorphonuclear leukocyte chemotaxis in early proliferative phase.

Basic fibroblast growth factor: peritoneal and follicular fluid levels and its effect on early embryonic development.

OBJECTIVE: To investigate the effect of basic fibroblast growth factor (FGF) on preimplantation embryos and to evaluate the levels of basic FGF in follicular and peritoneal fluid. DESIGN: Prospective study. SETTING: University-based laboratory. PATIENT(S): Follicular fluids (FFs) were obtained from women undergoing ovulation induction (n = 62) and peritoneal fluids were obtained from women with (n = 49) or without (n = 12) endometriosis. INTERVENTION(S): The effect of basic FGF on mouse embryos was assessed. Basic FGF concentrations were measured in pre-hCG and post-hCG FFs and in peritoneal fluids. MAIN OUTCOME MEASURE(S): Two-cell murine embryos were treated with basic FGF and followed for the rate of blastocyst formation and embryo hatching. Follicular and peritoneal fluid basic FGF levels were measured by ELISA. RESULT(S): Basic FGF (10 ng/mL) decreased the rate of blastocyst formation and embryo hatching. The level of basic FGF did not change in the FF around ovulation, and there was no correlation between FF basic FGF levels and reproductive parameters, with the exception of age. The levels of basic FGF in the peritoneal fluid of women with or without endometriosis were not different. CONCLUSION(S): Basic FGF is present in follicular and peritoneal fluids, but its concentration in these fluids does not change during the menstrual cycle or in the presence of endometriosis. Basic FGF inhibits murine preimplantation embryonic development at concentrations 10-100 times higher than the levels detected in follicular and peritoneal fluids.

The peritoneal fluid levels of interleukin-12 in women with endometriosis.

PROBLEM: Interleukin-12 (IL-12) is produced mainly by monocytes/macrophages, and it induces proliferation and cytotoxicity of T-cells and natural killer cells. In women with endometriosis, natural killer cell activity in the peritoneal fluid is significantly decreased. We aimed to measure the peritoneal fluid level of IL-12 in endometriosis. METHOD OF STUDY: We measured IL-12 levels in peritoneal fluid samples from women with or without endometriosis and in supernatants from endometrial stromal, ovarian stromal, and mesothelial cell cultures, using a high-sensitivity enzyme-linked immunosorbent assay. RESULTS: The median concentration of IL-12 in the peritoneal fluid of women with endometriosis was 1.1 pg/ml (range, 0.2-5.5) and was 1.6 pg/ml (range, 0.4-2.8) in women without endometriosis, not a statistically significant difference. IL-12 was not detected in the supernatants of endometrial stromal, ovarian stromal, and mesothelial cell cultures. CONCLUSION: Concentrations of IL-12 in the peritoneal fluid of women with or without endometriosis are low, but they are detectable and are not affected significantly by the presence of endometriosis.