despite many years of research efforts and impressive progress in knowledge of mechanisms of endometriosis development , the etiopathogenesis of the disease and exact cause of infertility in patients suffering from endometriosis still remain poorly understood .
none of the theories and models of endometriosis pathogenesis provide definitive explanation of the disease development , considering its different manifestations and various localizations .
recently published studies present new data on potential role of free radicals in endometriosis pathophysiology .
although the origin of the oxidative stress occurring in the peritoneal cavity in endometriotic patients is unknown , accumulating data suggest that increased iron levels , together with apoptotic endometrial fragments and activated macrophages , may promote prooxidant environment .
in addition , oxidative stress in endometriotic patients may potentially be induced by environmental factors , including dioxins or heavy metals [ 1 , 2 ] . in our preliminary work
we found significantly increased levels of ox - ldl in peritoneal fluid of women with stage iii / iv endometriosis compared to patients with follicle ovarian cysts .
however , peritoneal fluid oxldl concentrations did not differ significantly between patients with minimal / mild endometriosis and women from the reference group .
murphy et al .   showed increased low - density lipoprotein ( ldl ) oxidation in peritoneal fluid of patients with endometriosis , which may be a result of peritoneal cavity macrophages hyperactivity .
it was also proved that oxidized ldls stimulate monocyte chemotactic protein-1 ( mcp-1 ) expression in mesothelial and endometrial cells which provides direct evidence of oxidative stress role in etiopathogenesis of the disease . increased concentrations of lipid peroxidation end products , malondialdehyde ( mda ) , 8-isoprostane , and 25-hydroxycholesterol , were found in peritoneal fluid of infertile women with endometriosis [ 610 ] .
serum of patients with endometriosis , compared to healthy women , contains also significantly higher 8-isoprostane levels .
murphy et al .   showed that peritoneal fluid of patients with endometriosis contains increased concentration of lysophosphatidylcholine , another lipid peroxidation product with confirmed chemotactic properties for monocytes .
mda and 7-hydroxynonenal ( hne-7 ) expression were increased in endometriosis implants tissue ; however , both lipid proteins are also expressed in eutopic endometrium .
concentrations of antibodies against lipid peroxidation products were found to be increased in serum of women with endometriosis , with no immunoglobulins detected in their peritoneal fluid .
serum of women with endometriosis contains also elevated concentration of lipid hydroperoxide ( looh ) , and its levels correlate positively with the stage of the disease according to revised american fertility society classification .
peritoneal fluid of endometriotic patients contains oxidatively modified protein - lipid complexes , showing both chemotactic properties and ability to stimulate selected cytokines production . however , there are relevant data published in the literature according to which the concentrations of mda and mda - cu complexes demonstrate no significant differences , being comparable in peritoneal fluid of patients with and without endometriosis , showing also no significant correlation with the stage of the disease [ 1618 ] .
no differences were also found in peritoneal fluid concentration of another lipid peroxidation product , cholest-3,5-dien-7-one .
the objective of the study was to assess concentrations of oxidized low - density lipoproteins ( oxldl ) in peritoneal fluid ( pf ) of women with endometriosis .
clinically and histologically confirmed diagnosis established the following groups : women with endometriosis ( e , n = 110 ) and as the reference groups : patients with simple serous ( r1 , n = 78 ) and dermoid ( r2 , n = 41 ) ovarian cysts . in each case
the disease was found to be minimal ( e1 ) in 23 cases , mild ( e2 ) in 25 patients , moderate ( e3 ) in 39 women , and severe ( e4 ) in 23 cases .  
subjects were not given hormonal therapy and/or anti - inflammatory medications for at least 3 months before laparoscopy .
medical history of the patients and basic clinical examination showed no general chronic diseases , except for the condition , which was the indication for laparoscopy .
similarly , no significant difference was found in the phase of menstrual cycle of the time of laparoscopic procedures between women in all study groups .
all patients signed an informed consent , and the lublin medical university ethics committee approval was obtained for the study .
all visible pfs were aspirated during laparoscopy from the anterior and posterior cul - de - sacs , under direct vision to avoid blood contamination .
samples were immediately centrifuged at 500  g for 5 minutes , and the supernatants were aspirated and stored at 70c until analysis .
oxldl concentration in the pf was measured in duplicate using a commercially available enzyme - linked immunoassay kit ( immundiagnostik ag , cat .
all data were tested with the shapiro - wilk test for normality . because data were not normally distributed , statistical significance between e and r groups was determined with the mann - whitney u test .
data are presented as medians ( me ) , minima ( min ) , maxima ( max ) , and lower and upper quartiles .
concentrations of oxldl in pf of patients with endometriosis were significantly higher compared to women with serous ovarian cysts ( p = 0.03 ) .
however , no significant difference in the pf oxldl levels was found between patients with endometriosis and women with dermoid ovarian cysts ( p = 0.4 ) .
levels of oxldl in pf of women with serous ovarian cysts were similar to those noted in patients with dermoid cysts ( figure 1 , table 1 ) . by analyzing concentrations of oxldl in pf of women with different stages of the disease
, it was noted that they were higher only in the subgroup of patients with stage iv endometriosis as compared to women with ovarian serous cysts .
no significant differences were found between concentrations of oxldl in pf of women with different stages of the disease ( table 2 ) .  
pf oxldl concentration did not differ significantly between the subgroups of women in the follicular and the luteal phase of the menstrual cycle ( me , range : 71.5 , 1.21470  ng / ml versus 80.3 , 16.71870  ng / ml , p = 0.5 ) .
in our work , we demonstrated that peritoneal fluid oxldl concentration was significantly higher in patients with endometriosis than in women with serous ovarian cysts ; however , it did not differ significantly as compared to subjects with dermoid cysts . after analysis of data obtained in women with different stages of the disease , it was noted that these results are found only in patients with severe endometriosis . in case of minimal , mild , and moderate disease ,
to our knowledge , only murphy and colleagues investigated the possible role of oxldl in the pathogenesis of endometriosis .
based on a small number of cases , they found increased oxidation of low - density lipoprotein in women with pelvic endometriosis and increased levels of oxldl in the pf of patients with this disease .
our results agree with these findings . however , our data suggest that only the severe stage of endometriosis is associated with increased oxidation of low - density lipoprotein in the peritoneal cavity , probably as the result of an imbalance in prooxidant / antioxidant pf systems .
shanti et al .   demonstrated that women with endometriosis had increased serum concentrations of autoantibodies to markers of oxidative stress including oxldl .
data from our work indirectly confirm these results . based on many findings , there is an emerging concept of treating endometriosis as an autoimmune disease .
an increased incidence of endometriosis was observed in the group of women with autoimmune diseases such as multiple sclerosis , lupus erythematosus , psoriasis , crohn 's disease , hypothyroidism , hyperthyroidism , and rheumatoid arthritis .
endometriosis shares many similarities with other autoimmune diseases including elevated levels of cytokines , decreased cell apoptosis , and t- and b - cell abnormalities .
a variety of autoantibodies have been detected in patients with endometriosis patients , which suggests a polyclonal activation of b cells .
the most commonly reported types are antiendometrial , antiovarian antibodies , and autoantibodies against phospholipids , histones , and nucleotides
. other similarities between endometriosis and autoimmune diseases include familial occurrence , tissue damage , preponderance of females , and multiorgan involvement [ 21 , 22 ] .
lipid peroxidation processes are closely associated with the pathophysiology of autoimmune diseases . therefore , increased levels of oxidized ldl in pf of women with endometriosis support the theory of treating endometriosis as an autoimmune disease .
oxidized ldl induces secretion of numerous proinflammatory cytokines including macrophage colony - stimulating factor ( m - csf ) , interleukin-6 ( il-6 ) , and tumor necrosis factor  ( tnf- ) .
concentrations of these cytokines were found to be elevated in the pf of patients with endometriosis .
we can speculate that increased levels of oxidized ldl in the peritoneal cavity of women with severe endometriosis may be one of the factors responsible for increased levels of m - csf , il-6 , and tnf- in pf .
elevated pf concentrations of these cytokines promote adhesion , invasion , proliferation , and angiogenesis of ectopic endometrium and create an inflammatory environment in the peritoneal cavity in women with endometriosis .
.   demonstrated that oxldl caused an increase in accumulation of monocyte chemotactic factor-1 ( mcp-1 ) in the medium of cultured mesothelial and endometrial cells .
they also found that cells cultured in the presence of pf from endometriosis patients secreted more mcp-1 than those cultured with pf from subjects without the disease .
therefore , we hypothesize that increased concentration of oxldl may be responsible for , as demonstrated in other studies , higher concentrations of mcp-1 in the pf of women with endometriosis .
stimulation of mcp-1 production by increased pf levels of oxidized ldl may hypothetically be another factor responsible for the creation of proinflammatory environment in the peritoneal cavity of patients with endometriosis .  
unfavorable changes in lipid profile are present not only in the pf of women with endometriosis .
it has been recently shown that plasma of patients with this disease contains higher concentrations of total cholesterol , low - density lipoproteins , high - density lipoproteins ( hdl ) and triglycerides as compared to healthy women .
although all lipoproteins were significantly elevated in endometriosis patients , the difference was most substantial for ldl levels , which were 38% higher in women with endometriosis .
verit et al .   found that patients with endometriosis displayed significantly lower serum levels of hdl and higher levels of triglycerides , total cholesterol , and ldl than women without the disease .
they also demonstrated that serum of women with endometriosis is characterized by significantly lower activity of paraoxonase-1 ( pon-1 ) , which negatively correlated with the progression of the disease .
this hdl - associated antioxidant enzyme with paraoxonase activity prevents ldl and hdl oxidation and is also responsible for the antioxidant effect of hdl .
therefore , authors speculated that unfavorable lipid profile combined with lower pon-1 activity in women with endometriosis may contribute to the increased susceptibility for the development of atherosclerosis . in conclusion ,
oxldl levels were significantly higher in the peritoneal fluid of patients with severe endometriosis than in women with serous ovarian cysts .
this suggests that disrupted oxidative status in the peritoneal cavity of women with endometriosis may play a role in the etiopathogenesis of the more advanced stages of the disease .
however , it can not be excluded that high oxldl levels are the result of more oxidant environment in the peritoneal cavity of patients with severe endometriosis than with less advanced disease .
 the etiopathogenesis of endometriosis still remains unknown . 
 recent data provide new valuable information concerning the role of oxidative stress in the pathophysiology of the disease . 
 it has been proved that levels of different lipid peroxidation end products are increased in both peritoneal fluid ( pf ) and serum of endometriotic patients . 
 we assessed the concentration of oxidized low - density lipoproteins ( oxldl ) in pf of 110 women with different stages of endometriosis and 119 women with serous ( n = 78 ) or dermoid ( n = 41 ) ovarian cysts , as the reference groups . 
 pf oxldl levels were evaluated by elisa . 
 we found that concentrations of oxldl in pf of endometriotic women were significantly higher compared to women with serous but not dermoid ovarian cysts . 
 interestingly , by analyzing concentrations of oxldl in women with different stages of the disease , it was noted that they are significantly higher only in the subgroup of patients with stage iv endometriosis as compared to women with ovarian serous cysts . in case of minimal , mild , and moderate disease , 
 pf oxldl levels were similar to those noted in reference groups . 
 our results indicate that disrupted oxidative status in the peritoneal cavity of women with endometriosis may play a role in the pathogenesis of advanced stages of the disease . 