Department of Gynecology and Obstetrics, Emory University, Atlanta, Georgia, USA
Address for correspondence: Sampath Parthasarathy, Ph.D., Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322. Voice: 404-727-8604; fax: 404-727-8615.
spartha{at}emory.edu
Retrograde menstruation has been suggested to be the cause for
the presence of endometrial cells in the peritoneal cavity.
However, little is known about the events that lead to the adhesion
and growth of these cells that ultimately result in endometriosis,
considering the fact that the disease occurs only in certain
women despite the common occurrence of retrograde menstruation
in most women. We postulate that, in normal women, the endometrial
cells and tissue that arrive in the peritoneal cavity during
menstruation are effectively removed by macrophages that are
chemoattracted and become resident tissue macrophages in the
peritoneal cavity. In contrast, the peritoneal macrophages in
women with endometriosis are nonadherent and ineffectively scavenged,
resulting in the sustained presence and growth of the endometrial
cells. We also postulate that the peritoneal fluid is not a
passive reservoir of the factors secreted by cells of the peritoneum,
but actively promotes endometriosis. The peritoneal fluid is
rich in lipoproteins, particularly low-density lipoprotein,
which generates oxidized lipid components in a macrophage-rich
inflammatory milieu. The oxidants exacerbate the growth of endometriosis
by inducing chemoattractants such as MCP-1 and endometrial cell
growth-promoting activity. We provide evidence for the presence
of oxidative milieu in the peritoneal cavity of women with endometriosis,
the nonscavenging properties of macrophages that are nonadherent,
and the synergistic interaction between macrophages, oxidative
stress, and the endometrial cells. For example, the peritoneal
fluid lipoproteins of subjects with endometriosis have increased
the propensity to undergo oxidation as compared with plasma
lipoproteins, and the subjects also have increased titer of
autoantibodies to oxidatively modified proteins. If the oxidative
proinflammatory nature of the peritoneal fluid is an important
mediator of endometriosis growth, anti-inflammatory agents and
antioxidants might afford protection against endometriosis.
