Role In Pathogenesis Of Endometriosis Research Articles

The mIRNA519a-3p and NKG2D in endometriosis.

Background: Natural killer (NK) cells play a role in pathogenesis of endometriosis. Lower expressions of NK cells receptor group 2D (NKG2D) ligands inhibits cytotoxic activity of NK cells; a common immunity avoidance mechanism in neoplasms. Literatures have proven miRNAs regulatory effect on NKG2D expression. There has been no specific biomarker for diagnosing endometriosis. Non-invasive means of diagnosing endometriosis may reduce well-known risks of invasive method of diagnosis and yield better results.
 Purpose: To investigate the correlation between miRNA-519a-3p expression with NKG2D ligands (MICA, MICB, ULBP 1-6) on endometriosis and non-endometriosis patients.
 Methods: This was a cross-sectional study held in five centers: dr. Cipto Mangunkusumo General Hospital, Pelni Hospital, Bunda Hospital, YPK Mandiri Hospital, and Primaya Evasari Hospital from October 2020 to July 2021. miRNA and NKG2DL analysis were done in Human Reproduction, Infertility and Family Planning (HRIFP) cluster at IMERI FKUI.
 Results: We obtained 19 patients in each study groups. NKG2D ligands and miRNA519a-3p relative expressions were not significantly different (p > 0.05). Increased miRNA519a-3p expression negatively affected NKG2D ligands expression. A decrease in ULBP1 and an increase in ULBP2 increased the probability for endometriosis. NKG2D ligands expression may be influenced by infection, pro-inflammatory cytokine production, dan polymorphism. NKG2D ligands expression level can be different depending on the origin of the sample. Lower expression of miRNA519a-3p indirectly inhibits tumor apoptosis by lowering NKG2D ligands, caspase, or mRNA.
 Conclussion: We did not manage to establish a correlation between NKG2D ligands with miRNA519a-3p in endometriosis and non-endometriosis patients.

Effectiveness of Gamma Oryzanol on prevention of surgical induced endometriosis development in rat model

Infertility is believed to be triggered by endometriosis whose pathophysiology and the etiology is still unknown. Certain genes play pivotal roles in pathogenesis of endometriosis. Natural products and plants are used as important sources for production of new drugs. The current study assesses the effects of gamma-oryzanol (GO) in a rat model with surgically induced endometriosis. The experimental endometriosis was induced in 24 wistar rats, and the animals were subsequently subdivided into endometriosis-sole (endom group), 3000 and 6000 µg/kg GO (GO-3000 and GO-6000) and Vit C groups. The protein levels of estrogen receptor-alpha (ER-α), Steroidogenic factor 1 (SF1), Sirtuin 1 (SIRT1), heme oxygenase 1 (HO1), light chain 3 (LC3B) and Beclin1 (BECN1) were assessed. TUNEL staining was used for detecting the apoptosis rate. The results revealed that protein levels of SF1, HO1, and total LC3B significantly (P < 0.05) decreased in GO-6000-treated groups compared to endom group. Moreover, the protein level of BECN1 and SIRT-1 significantly (P < 0.05) increased in GO-6000-treated groups compared to endom group. GO treatment did not imply any significant difference (P > 0.05) concerning the protein levels of ER-α. The TUNEL staining results showed higher TUNEL-positive cells reactions in the rats treated with GO-6000 and Vit C. Thus, GO is involved in improving condition rats involved with endometriosis through modulation in the protein levels of some molecules and also induction of apoptosis.

Differential expression and functional analysis of micro RNAs in &lt;em&gt;Papio anubis&lt;/em&gt; induced with endometriosis for early detection of the disease

Endometriosis is a common gynecological disorder affecting approximately 10% of women of reproductive age who often experience chronic pelvic pain and infertility. Laparoscopy, which is invasive and expensive, is the gold standard for diagnosis of endometriosis. A simple minimally-invasive test for endometriosis-specific biomarkers which is yet to be realized would offer a timely and accurate diagnosis for the disease thereby allowing early treatment intervention. Although aberrant microRNA expression has been implicated in endometriosis in several studies, conflicting results have been reported. This study hypothesized that the use of an appropriate animal model will provide a unique entry point for the discovery of biomarkers for early diagnosis of endometriosis. The study aimed at identifying miRNAs that are differentially expressed in eutopic endometrium of induced endometriosis in Papio anubis for early detection of endometriosis. Female adult baboons (n = 3) were induced with endometriosis by intraperitoneal inoculation of autologous menstrual endometrium. We sequenced small RNA samples obtained from normal (control) and diseased eutopic endometrium. Quality reads from the sequences were subjected to differential expression analysis to identify dysregulated microRNAs and genes from other non-coding small RNA in the samples using a bioinformatics approach. Through in-silico analysis, gene targets of the dysregulated miRNA and their functions were determined. Our findings show significant high expression of seven microRNAs namely miR-199a-3p, miR-145-5p, miR-214-3p, miR-143-3p, miR-125b-5p, miR-199a-5p and miR-10b-5p. The study also reveals five microRNAs that were significantly down regulated and they include miR-29b-3p, miR-16-5p, miR-342-3p, miR-378a-3p and let-7g-5p. Seventeen genes from non-coding small RNAs were significantly dysregulated. The dysregulated microRNAs and genes play important roles in pathogenesis of endometriosis. Our findings indicate that specific miRNA signatures are associated with endometriosis, and the dysregulated miRNAs could constitute new and informative biomarkers for early diagnosis of endometriosis.

The levels of matrix metalloproteinase-9 and neutrophil gelatinase-associated lipocalin in different stages of endometriosis

This study was designed to explore matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) levels and MMP-9/NGAL ratio in women with and without endometriosis diagnosed surgically and/or histopathologically. The correlation between biomarkers and the severity of the disease is analysed. The revised American Fertility Society classification system was used to determine the severity of endometriosis. Serum MMP-9 and Ca125, urine NGAL levels were measured in all participants. Serum MMP-9 levels were significantly higher in the study group (n = 60) compared to controls (n = 31) (15.0 pg/mL (6.0–143.0) vs. 12.0 (4.0–18.0), respectively; p=.002). MMP-9 levels were significantly higher in severe endometriosis compared to mild endometriosis subgroups (p<.001). No significant difference was found between NGAL levels in study and control groups (p>.05). The diagnostic value of MMP-9 and NGAL is not superior than CA-125 for endometriosis. Nevertheless, MMP-9 might be a potential predictive marker for advanced stage of the disease.Impact StatementWhat is already known on this subject? The gold standard diagnostic test for diagnosis of endometriosis is laparoscopy combined with histopathological confirmation of eutopic endometrial glands and/or stroma. Both invasiveness and possible accompanying complications limit the preference regarding the surgical approach. Among non-invasive markers none has been accepted as gold standard neither for diagnosis nor for determining the severity of the disease. MMPs are extracellular endopeptidases, which have a significant role in degradation and remodelling of extracellular matrix for cellular migration and invasion. Among these, MMP-9 has been shown to be higher in eutopic/ectopic endometrial tissue in women with endometriosis and has been suggested to have a role in pathogenesis of endometriosis by promoting invasion of the endometriotic lesions. NGAL is an acute phase protein, which is involved in a variety of physiological and pathophysiological processes. The molecule has also been revealed to correlate with endometriosis pathophysiology through the epithelial–mesenchymal transition process which is the basis for the onset of endometriosis. But also, NGAL which composes a complex with MMP-9 (MMP-9 and NGAL complex), has been shown to protect MMP-9 from autodegradation in vitro which might be a contributing factor for endometriosis pathophysiology.What the results of this study add? MMP-9 cut-off level for prediction of severe endometriosis is a novel finding obtained from this study with acceptable sensitivity and specificity. On the other hand, NGAL seems to have no significant value either for diagnosis of for determining severity of the disease. After all, MMP-9 might be an easy use acceptable biomarker for endometriosis but further studies on larger populations are needed.What the implications are of these findings for clinical practice and/or further research? MMP might be a potential non-invasive predictive marker for advanced stage disease.

Expression and role of hScrib in endometrium, endometriosis, and endometrial adenocarcinoma.

To explore the role of hScrib in the pathogenesis of endometriosis.This was a retrospective study of 240 women in our hospital between January 2014 and January 2017. The expression of hScrib in endometrium (EM), endometriosis (EMs), and endometrial adenocarcinoma (EC) was investigated, and compared the differences among them. Serum levels, protein expressions, localizations, and correlations of hScrib and E-cadherin were determined.The levels of serum soluble hScrib and E-cadherin were significantly highest in EC, followed by EMs, and healthy women (P < .05). hScrib protein content was opposite result in 3 tissues (P < .05), and was negatively correlated with r-AFS stage in EMs. The location changed from membrane to cytoplasm. Co-localization of hScrib with E-cadherin was found at extensive cell–cell boundaries in EMs.hScrib and E-cadherin may be as new diagnostic markers of endometriosis. Low expression of hScrib leads to the loss of cell polarity and stability. Also, hScrib may induce EMT through regulating E-cadherin, might play an important role in pathogenesis of endometriosis.

Involvement of endoplasmic reticulum stress in regulation of endometrial stromal cell invasiveness: possible role in pathogenesis of endometriosis.

Endoplasmic reticulum (ER) stress is known to reduce invasiveness in some cancer cells by inhibiting the AKT/mTOR pathway. A previous study from our laboratory suggested that ER stress is promoted by progesterone in human endometrial cells, which suggests that progesterone may inhibit endometrial cell invasiveness by up-regulating ER stress. Therefore, aberrant ER stress in response to progesterone may contribute to the altered invasiveness found in endometriotic tissues. To test this hypothesis, we elucidate whether ER stress is involved in regulation of human endometrial cell invasiveness through the AKT/mTOR pathway and if this involvement is associated with altered invasiveness in endometriotic cells. Specifically, we sought to determine the effects of ER stress on AKT/mTOR pathway by evaluating ER stress-mediated CHOP/TRIB3 signaling, a negative regulator of AKT. We found that ER stress marker GRP78 expression increased with CHOP and TRIB3 expression in normal endometrial stromal cells (NESCs) treated with tunicamycin, and this increase was accompanied by decreased AKT and mTOR activity and cellular invasiveness. Similarly, progesterone increased GRP78, CHOP and TRIB3 expression in NESCs. Subsequently, inhibition of AKT and mTOR activity decreased cellular invasiveness. This progesterone-induced decrease in cellular invasiveness was reversed by inhibition of ER stress. In contrast, progesterone did not change CHOP, TRIB3, AKT, mTOR or invasiveness in endometriotic cyst stromal cells. In contrast to normal endometrium, endometriotic tissues showed no changes in CHOP, TRIB3 and invasion-related proteins (MMP2 and MMP9) expression throughout the menstrual cycle. Taken together, our findings indicate that abnormal ER stress response to progesterone increased endometriotic stromal cell invasiveness via the AKT/mTOR pathway.

Estradiol Reduces Connexin43 Gap Junctions in the Uterus during Adenomyosis in Cows.

Adenomyosis is defined as the presence of glandular foci external to the endometrium of the uterus, either in the myometrium or/and perimetrium, depending on the progress of this dysfunction. To date, we showed that steroids secretion and prolactin expression and proliferative processes are disturbed during uterine adenomyosis in cows. During endometriosis in eutopic endometrium in women, gap junctions are down regulated. The transmembrane gap junction protein, connexin (Cx43) is necessary for endometrial morphological, biochemical and angiogenic functions. The aim of this study is recognition of adenomyosis etiology by determination of the role of Cx43 in this process. Immunolocalization and comparison of Cx43 mRNA and protein expression in healthy (N=9) and adenomyotic uterine tissue (N=9), and Cx43 mRNA expression (real time PCR) in uterine stromal - myometrium co-culture under 24-hour stimulation with 17-beta estradiol (10-7M) isolated from healthy (N=5) and adenomyotic (N=5) cows were determined. Cx43 was localized in healthy and adenomyotic uteri. mRNA and protein expression was down-regulated in uterine tissue in adenomyotic compared with healthy cows (p<0.05). Estradiol stimulated Cx43 mRNA expression in myometrial cell culture and co-culture of stromal and myometrial cells in adenomyotic compared with healthy cows (p<0.05). In summary, down-regulation of Cx43 expression in the junction zone might play an important role in pathogenesis of adenomyosis. Estradiol modulates gap junctions during adenomyosis.

Association of the Precursor of Interleukin-1β and Peritoneal Inflammation-Role in Pathogenesis of Endometriosis.

The most important proinflammatory cytokine is interleukin (IL)-1β, however its precursor, prointerleukin-1β (proIL-1β), can also potentiate inflammatory state. The aim of this study was to explore the involvement of proIL-1β in pathogenesis of endometriosis. For this purpose, we evaluated concentrations of proIL-1β, IL-1β, and soluble IL-1 receptor type 2 (sIL-1R2) in peritoneal fluid (PF) and macrophage culture medium of women with endometriosis. PF from 55 women with and without endometriosis was collected during laparoscopy. Peritoneal macrophages were cultured in basal and stimulated with lipopolysaccharide (LPS) conditions. Concentrations of cytokines were measured with enzyme-linked immunosorbent assays (ELISA). PF proIL-1β and IL-1β levels in endometriosis women were higher than in the control. Higher basal and stimulated macrophage secretion of cytokines in endometriosis patients than in the control was observed. However, in endometriosis, there was a higher level of proIL-1β than for the mature molecule. Additionally, lower PF and macrophages culture medium sIL-1R2 levels were observed in women with endometriosis. Abnormal proIL-1β concentration in PF and higher macrophage secretion can escalate peritoneal inflammation and endometriosis formation. The results are presented as a total IL-1β, which is a sum of proIL-1βand IL-1β, and we believe that it reflects the actual cytokine production. The imbalance among all studied cytokines in endometriosis may be linked with an ability to transform acute inflammation to the chronic inflammation.

CRISPLD2 is a target of progesterone receptor and its expression is decreased in women with endometriosis.

Endometriosis, defined as the presence of endometrial cells outside of the uterine cavity, is a major cause of infertility and pelvic pain, afflicting more than 10% of reproductive age women. Endometriosis is a chronic inflammatory disease and lipopolysaccharide promotes the proliferation and invasion of endometriotic stromal cells. Cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) has high affinity for lipopolysaccharide and plays a critical role in defense against endotoxin shock. However, the function of CRISPLD2 has not been studied in endometriosis and uterine biology. Herein, we examined the expression of CRISPLD2 in endometrium from patients with and without endometriosis using immunohistochemistry. The expression of CRISPLD2 was higher in the secretory phase in human menstrual cycle compared to proliferative phase. The expression of CRISPLD2 was significantly decreased in the endometrium of women with endometriosis in the early secretory phase compared to women without endometriosis. The increase of CRISPLD2 expression at the early secretory and dysregulation of its expression in endometriosis suggest progesterone (P4) regulation of CRISPLD2. To investigate whether CRISPLD2 is regulated by P4, we examined the expression of the CRISPLD2 in the uteri of wild-type and progesterone receptor knock out (PRKO) mice. The expression of CRISPLD2 was significantly increased after P4 treatment in the wild-type mice. However, CRISPLD2 expression was significantly decreased in the (PRKO) mice treated with P4. During early pregnancy, the expression of CRISPLD2 was increased in decidua of implantation and post-implantation stages. CRISPLD2 levels were also increased in cultured human endometrial stromal cells during in vitro decidualization. These results suggest that the CRISPLD2 is a target of the progesterone receptor and may play an important role in pathogenesis of endometriosis.

Increased expression of the pluripotency markers sex-determining region Y-box 2 and Nanog homeobox in ovarian endometriosis.

BackgroundThe precise etiology of endometriosis is not fully understood; the involvement of stem cells theory is a new hypothesis. Related studies mainly focus on stemness-related genes, and pluripotency markers may play a role in the etiology of endometriosis. We aimed to analyze the transcription pluripotency factors sex-determining region Y-box 2 (SOX2), Nanog homeobox (NANOG), and octamer-binding protein 4 (OCT4) in the endometrium of reproductive-age women with and without ovarian endometriosis.MethodsWe recruited 26 women with laparoscopy-diagnosed ovarian endometriosis (endometriosis group) and 16 disease-free women (control group) to the study. Endometrial and endometriotic samples were collected. SOX2, NANOG, and OCT4 expression were analyzed with quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry.ResultsCompared to the control group, SOX2 mRNA and protein expression was significantly higher in the eutopic endometrium of participants in the endometriosis group. In the endometriosis group, SOX2 and NANOG mRNA and protein expression were significantly increased in ectopic endometrium compared with eutopic endometrium; there was a trend towards lower OCT4 mRNA expression and higher OCT4 protein expression in ectopic endometrium.ConclusionsThe transcription pluripotency factors SOX2 and NANOG were overexpression in ovarian endometriosis, their role in pathogenesis of endometriosis should be further studied.

CD4+ CD25+ FOXP3+ regulatory T cells in peripheral blood and peritoneal fluid of patients with endometriosis

Is endometriosis associated with changes in CD4⁺ CD25⁺ FOXP3⁺ regulatory T cells (Treg cells)? Endometriosis is associated with disturbed compartmentalization of CD25(high) FOXP3⁺ Treg cells. Endometriosis is associated with an abrogated immune response and displays some features of an autoimmune disorder. Treg cells play a part in the development of autoimmune reactions; however, their role in pathogenesis of endometriosis is still poorly recognized. Case-control study comparing 17 women with laparoscopically and histopathologically confirmed ovarian endometriosis with 15 control women without visible endometriosis foci, pelvic inflammation or related pathology who were subjected to laparoscopic surgery between 2010 and 2011. Peripheral blood and peritoneal fluid were collected during laparoscopy and T cell subpopulations were analysed by flow cytometry using specific monoclonal antibodies recognizing CD4⁺, CD25⁺ and FOXP3⁺ markers. The percentage of CD25(high) FOXP3⁺ Treg cells was significantly decreased in the peripheral blood of women with ovarian endometriosis compared with control women. On the other hand, the proportion of these cells was significantly increased in the peritoneal fluid of women with endometriosis. The present study is limited to patients with ovarian endometrioma and further investigations are needed, including patients with lower grade of endometriosis. The present results suggest that Treg cells may play a part in immunopathogenesis of endometriosis being responsible for abrogated local cellular immune responses and facilitation and development of autoimmune reactions. Treg cells may be thus a potential target in the treatment of endometriosis. This study was supported by 1M15/N/2011 and NK1W grants from the I Faculty of Medicine, Warsaw Medical University. None of the authors has any competing interests to declare.

Imbalance in Cytokines from Interleukin‐1 Family – Role in Pathogenesis of Endometriosis

To assess whether interleukin (IL)-1beta, IL-18 and interleukin-1 converting enzyme (ICE) are involved in the pathogenesis of endometriosis. Peritoneal fluid (PF) was obtained from 85 women with and without endometriosis. Peritoneal macrophages were cultured and the culture media collected. IL-1beta, IL-18 and ICE levels were measured by the enzyme-linked immunosorbent assay (ELISA). Levels of IL-1beta and ICE in PF of women with endometriosis were higher than those in the control group. However, PF level of IL-18 was significantly lower in the study group than in the controls. Higher secretion of IL-1beta by peritoneal macrophages and lower IL-18 and ICE in endometriosis patients than in control were observed. Following lipopolysaccharide (LPS) stimulation, the macrophages secreted more IL-1beta, IL-18 and ICE in all groups. The results pointed to impairment of the secretion of the IL-1 cytokine family in endometriosis. Invalid IL-1beta and IL-18 maturation by ICE may be an important pathogenic factor in endometriosis.

Association of E-cadherin single nucleotide polymorphisms with the increased risk of endometriosis in Indian women

The objective of the present study was to investigate the association between gene E-cadherin single nucleotide polymorphisms (SNPs) and risk of developing endometriosis in Indian women and to evaluate the role of E-cadherin expression in the pathophysiology of endometriosis. A genetic association study was conducted in 715 endometriosis cases and 500 controls of Indian origin. We genotyped -160 C/A, +54 C/T and -347 G/GA SNPs of gene E-cadherin by PCR-sequencing and PCR-restriction fragment length polymorphism techniques. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D') for pair-wise linkage disequilibrium (LD) were assessed by Haploview Software. In addition, to better understand genetic contributions to the pathophysiology of endometriosis, the expression pattern of E-cadherin in the endometrium of women with and without endometriosis was analyzed by western blot and immunohistochemical analysis. The frequencies of -347GA/GA (P = 0.026) and -160A/A (P = 0.0019) genotypes and -347G/-160A/+54C (P = 0.007) and -347GA/-160A/+54C (P < 0.0001) haplotypes were significantly different between patients and controls. Strong LD was observed between -347G/GA and -160C/A loci (D' = 0.64) when compared with -347G/GA and +54C/T (D' = 0.585) or -160C/A and +54C/T (D' = 0.05) loci in cases. Furthermore, increased membranous E-cadherin expression was observed in cases than in controls. The expression seems to be genotype dependent. In conclusion, the E-cadherin -347GA/GA and -160A/A genotypes and -347GA/-160A/+54C and -347G/-160A/+54C haplotypes may jointly modify the risk of endometriosis in Indian women. In addition, the differential expression of E-cadherin may play an important role in pathogenesis of endometriosis.

Clinical implication of recent advances in our understanding of IL-17 and reproductive immunology

The identification of a novel helper T (Th)-cell subset, the IL-17-producing Th (Th17) cells, has provided new insight into our understanding of the molecular mechanisms of reproduction. IL-17 has an important role in induction of the protective immune response against extracellular bacteria or fungal pathogens. Th17 cells seem to participate in successful pregnancy processes. Th17 cells also play a pivotal role in pathogenesis of endometriosis, miscarriage, preterm labor and preeclampsia. Recent data show the reciprocal development of pathways between Th1/Th17 subsets and between Th17/Treg subsets, and the imbalance of Th17/Treg development has been reported in recurrent pregnancy loss and preeclampsia.

Relationship between ultrastructural features with the expression of connexin 43 in the uterine junction zone and pathogenesis of adenomyosis

to investigate the relationship between the ultrastructural features combined with the expression of connexin (Cx43) protein in uterine junction zone and pathogenesis of adenomyosis. from Nov. 2008 to Nov. 2009, 30 patients with adenomyosis (including 14 cases with proliferative endometrium and 16 cases with secretory endometrium) as study group matched with 30 women with cervical intraepithelial neoplasia (CIN) III treated by hysterectomy as control group were enrolled in this study in Affiliated Hospital to Inner Mongolia Medical College. The expression of Cx43 in uterine junction zone of patients with adenomyosis was detected by immunohistochemisty staining. The ultrastucture of eutopic endometrium, uterine junction zone and outer 1/3 myometrium in both groups without history of dilatation and curettage, C-section and uterine surgery were observed by using transmission electron microscopy. (1) the expression of Cx43 in proliferative and secretroy uterine junction zone were 0.133 ± 0.018 and 0.137 ± 0.021 in study group and 0.154 ± 0.016 and 0.141 ± 0.018 in control group, which reached statistical difference (P < 0.05). However, it didn't show significant expression of Cx43 between proliferative and secretory uterine junction zone in study or control group (P > 0.05). The expression of Cx43 in proliferative and secretory of eutopic endometrium of 0.067 ± 0.017 and 0.062 ± 0142 in study group were significantly lower than 0.094 ± 0.005 and 0.080 ± 0.005 in control group. It didn't show statistical difference of Cx43 expression between proliferative and secretroy eutopic endometrium in both group. The expression Cx43 in outer myometrium of proliferative phase were 0.184 ± 0.022 in study group and 0.188 ± 0.028 in control group, which did not show significant difference (P > 0.05). It also did not exhibit statistical difference of Cx43 expression in outer myometrium of secretory phase (0.178 ± 0.022, 0.191 ± 0.025, P > 0.05). (2) Morphological changes: the area of uterine smooth muscle cells of the uterine junction zone of (24.3 ± 1.6) microm(2) in study group were significantly increased than (21.8 ± 2.0) microm(2) in control group (P < 0.01). The length of the cell membrane dense plaques of (1.07 ± 0.17) microm in study group was significantly increased than (0.71 ± 0.07) microm in control group (P < 0.01). The myocytes exhibited cellular hypertrophy and disordered arrangement and fewer caveolae. There was cylindrical and dentate, chromatin margination, more heterochromatin in which muscle cells of nuclear surface of the uterine junction zone. Less cytoplasmic myofilaments and more intermediate filaments. Mitochondria were increased, the volume increased significantly vacuolization. The rough endoplasmic reticulum and Golgi apparatus were more prominent. Otherewise, mast cells and fibroblasts were close and glandular epithelial cells showed desmosome connection which villus thickening and dense. All features were more prominent at the junctional zone. the down-regulation of Cx43 expression and ultrastructure changes in the junction zone might play an important role in pathogenesis of adenomyosis.

Diesel Exhaust Exposure Enhances the Persistence of Endometriosis Model in Rats

Diesel exhaust (DE) is known to be one of the main causes of air pollution. Several studies have suggested that DE causes lung cancer, cardiovascular disease, abnormal reproductive function, and central nervous system damage as well as type I allergy in the airway. Type I allergy also plays a role in pathogenesis of endometriosis. In the present study, we examined the effect of exposure to DE on a rat model of endometriosis. Endometriosis was induced by autotransplantation of endometrium to the peritoneum in female Sprague-Dawley rats exposed to DE during prenatal and postnatal periods. Endometriotic lesions, normal peritoneum, and blood samples were obtained on days 4, 7, and 14 after autotransplantation. The extent of stromal proliferative lesions in the endometriosis model was greater in the rats of the DE exposure group than in those of the control group on day 14. Serum monocyte chemoattractant protein (MCP)-1levelwas significantlyhigher in ratswithendometriosis in the DE exposure group than in those in the control group on day 14. Results of this study suggest that DE exposure enhances the histologic and molecular pathology of endometriosis in rats.

P-351: Interferon-γ gene dinucleotide (CA) repeat polymorphism in patients with endometriosis

P-351: Interferon-γ gene dinucleotide (CA) repeat polymorphism in patients with endometriosis

P-338: Aberrant methylation in aromatase gene may be responsible for its aberrant expression in endometriotic stromal cells

Endometriosis is known as an estrogen-dependent disease. Up-regulation of aromatase expression in the endometriotic tissues has been demonstrated. Aberrant expression of aromatase may play a role in pathogenesis of endometriosis. In the present study, we examined aromatase expression in endometrial and endometriotic stromal cells. We tried to induce aromatase gene expression in endometrial stromal cells using a demethylation agent. We further characterized predicted CpG islands (CpGI) in upstream region of the aromatase gene.

The Distinct Activation of Activating Transcription Factor 2 (ATF2) may Play a Crucial Role in Pathogenesis of Endometriosis

Endometriosis is one of the commonest chronic gynecological disorders diagnosed in women of reproductive age. The pathogenetic factors of endometriosis still remain unclear. There is increasing evidence that endometriosis is inherited as a complex genetic trait in which multiple genes conferring disease susceptibility interact with each other and the environment to produce the phenotype. Furthermore, the signaling transduction pathway and transcriptional regulation of this disease are mostly uncharacterized.

132 Adhesive molecules role in pathogenesis of endometriosis — CD11b and CD62L expression on the peripheral blood and peritoneal fluid neutrophils surface

132 Adhesive molecules role in pathogenesis of endometriosis — CD11b and CD62L expression on the peripheral blood and peritoneal fluid neutrophils surface