Inducible nitric oxide synthase expression by peritoneal macrophages in endometriosis-associated infertility.
OBJECTIVE
Determine whether peritoneal macrophages from women with endometriosis-associated infertility express more inducible nitric oxide synthase (NOS2) and produce more NO than fertile controls.


METHODS
Unblinded clinical study.


METHODS
Nine infertile women with endometriosis and nine normal fertile women undergoing laparoscopy.


METHODS
Peritoneal fluid and macrophages were collected. Cells were also cultured with the NOS2 inducers interferon-alpha (IFN-alpha) or IFN-gamma plus lipopolysaccharide (LPS).


METHODS
Peritoneal fluid NO levels, peritoneal macrophage NOS activity, and peritoneal macrophage NOS2 protein expression.


RESULTS
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.


CONCLUSIONS
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.
Osborn
Barbara H
BH
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina 27705, USA.
Haney
A F
AF
Misukonis
Mary A
MA
Weinberg
J Brice
JB
D000818:Animals; D001202:Ascitic Fluid / Q000737:chemistry; D002460:Cell Line; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000201:enzymology*; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D012016:Reference Values
D016898:Interferon-alpha; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D007371:Interferon-gamma; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse