Inducible nitric oxide synthase expression by peritoneal macrophages in endometriosis-associated infertility

Osborn BH, Barbara H. Osborn, A F Haney, Haney AF, Misukonis MA, Mary A. Misukonis, Weinberg JB, Jason B. Weinberg, J. Brice Weinberg
Fertility and sterility · 2002 · vol. 77(1) , pp. 46–51 · doi:10.1016/s0015-0282(01)02940-5 · PMID:11779590 · W2005377182
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Peritoneal macrophages in endometriosis-associated infertility express inducible nitric oxide synthase, an enzyme involved in nitric oxide production.

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Abstract

ObjectiveDetermine whether peritoneal macrophages from women with endometriosis-associated infertility express more inducible nitric oxide synthase (NOS2) and produce more NO than fertile controls.DesignUnblinded clinical study.Patient(s)Nine infertile women with endometriosis and nine normal fertile women undergoing laparoscopy.Intervention(s)Peritoneal fluid and macrophages were collected. Cells were also cultured with the NOS2 inducers interferon-alpha (IFN-alpha) or IFN-gamma plus lipopolysaccharide (LPS).Main outcome measure(s)Peritoneal fluid NO levels, peritoneal macrophage NOS activity, and peritoneal macrophage NOS2 protein expression.Result(s)NOS enzyme activity was higher in peritoneal macrophages from endometriosis patients. Immunoblots demonstrated NOS2 protein only in peritoneal macrophages from women with endometriosis. Peritoneal fluid NO concentration was similar in the two groups, but total peritoneal fluid NO content was higher in endometriosis patients. After 3 days' culture, peritoneal macrophages from women with endometriosis produced more NO in response to IFN-alpha or IFN-gamma plus LPS than controls.Conclusion(s)Peritoneal macrophages from women with endometriosis-associated infertility express higher levels of NOS2, have higher NOS enzyme activity, and produce more NO in response to immune stimulation in vitro. As high levels of NO adversely affect sperm, embryos, implantation, and oviductal function, reducing peritoneal fluid NO production or blocking NO effects may improve fertility in women with endometriosis.

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Condition tags

endometriosisinfertility

MeSH descriptors

Infertility, Female Macrophages, Peritoneal Nitric Oxide Synthase Animals Ascitic Fluid Ascitic Fluid Cell Line Cells, Cultured Enzyme Induction Enzyme Induction Female Humans Infertility, Female Interferon-alpha Interferon-alpha Interferon-gamma Interferon-gamma Lipopolysaccharides Lipopolysaccharides Macrophage Activation

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