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Biomedical subjects

P Viganò

Publications and source records attributed to P Viganò.

At least 19 recordsLinked to original sources

Secretory endometrium highly expresses urocortin messenger RNA and peptide: possible role in the decidualization process.

BACKGROUND: Urocortin (UCN) gene expression and synthesis have been reported in epithelial and stromal cells of the human endometrium. In this study we evaluated (i) UCN messenger RNA (mRNA) expression and peptide production in uterine specimens collected throughout the endometrial cycle, (ii) UCN secretion after decidualization of cultured human endometrial stromal cells (HESCs) and (iii) the effect of UCN on endometrial decidualization. METHODS: HESCs were isolated from samples of human endometrium collected from healthy patients with normal menstrual cycle and cultured in presence of cAMP, 17-beta-estradiol (E(2)) + medroxyprogesterone acetate (MPA) and UCN. UCN levels were measured in endometrial extracts by an enzyme immunoassay, and changes of endometrial UCN mRNA expression were measured by RT-PCR analysis. RESULTS: UCN peptide concentrations and mRNA expression were highest in the secretory phase of the menstrual cycle (P < 0.001, late secretory versus early and late proliferative phase) and higher in the late than the early secretory phase (P < 0.01). After decidualization of HESC with cAMP or E(2) + MPA, UCN levels rose in parallel with prolactin concentrations by days 6 (P < 0.01, for all). Finally, the addition of UCN to HESCs, with or without E(2) + MPA, induced the release of prolactin. CONCLUSIONS: The evidence that (i) UCN is highly expressed in the secretory phase of the endometrial cycle; (ii) cAMP and E(2) + MPA modulate secretion of UCN and (iii) UCN induces HESCs decidualization together suggest a possible role for UCN in endometrial physiology.

Adult↗

Human decidual natural killer cells as a source and target of macrophage migration inhibitory factor.

The human uterine mucosa of early pregnancy is largely populated by CD56(bright) natural killer (NK) cells (uterine (u) NK cells). The specific functions of these cells are still unknown, but their interaction and response to foetal trophoblasts are thought to be important for the establishment of a successful pregnancy. The study reported herein shows that uNK cells respond to, and produce, macrophage migration inhibitory factor (MIF), a cytokine highly expressed in the human placenta and in the cyclic and pregnant endometrium. Recombinant human MIF reduced in a dose-dependent manner the cytolytic activity of purified uNK cells against K562 cells. RT-PCR, Western blot analysis and ELISA demonstrated the synthesis and secretion of the cytokine by uNK cells. Double immunofluorescence staining showed the presence of MIF in uterine CD56 + cells. Finally, neutralization of the endogenous cytokine by a polyclonal antibody resulted in a sharp increase in the cytolytic activity of uNK cells. These findings indicate the existence of a previously unrevealed paracrine and autocrine action of MIF on uNK cells and support its contribution to the immune privilege at the maternal-foetal interface.

Antibodies, Monoclonal↗

Cycling and early pregnant endometrium as a site of regulated expression of the vitamin D system.

In addition to its calciotropic function, the secosteroid 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has potent anti-proliferative/immunomodulatory effects on various tissues. Consistently, the enzyme that catalyzes the synthesis of 1,25(OH)(2)D(3), 1alpha-hydroxylase (1alpha-OHase) and the vitamin D receptor have a widespread tissue distribution. Among site-specific functions, the hormone has been suggested to be involved in uterine physiology. However, molecular analysis of the vitamin D system in normal endometrium throughout the menstrual cycle as well as its regulation in the context of endometrial physiological and pathological events have received very limited attention. Thus, we have studied expression, localization and regulation of 1alpha-OHase in human cycling and early pregnant endometrium. The capacity for 1alpha-hydroxylation and the presence of vitamin D receptor in endometrial cells have also been evaluated. The functional significance of these findings has been tested by evaluating gene expression of the catabolic enzyme, vitamin D 24-hydroxylase, and of the adhesion protein, osteopontin. Finally, to verify any potential dysfunction of the vitamin D system in endometriosis, a reproductive disease characterized by immune-mediated anomalies, we have analyzed expression of 1alpha-OHase in both eutopic and ectopic endometrium of affected patients. Results obtained showed that the active form of the 1alpha-OHase gene was expressed in human endometrial stromal cells independent of the cycle phase but with a significant increase in early pregnant decidua. A similar profile was observed for the protein, which was abundantly expressed in the cytoplasm of both endometrial stroma and epithelial glands. Both cycling and early pregnant endometrial cells also expressed the vitamin D receptor. In the same cells, 1alpha-OHase mRNA levels were significantly stimulated by the pro-inflammatory cytokine interleukin (IL)-1beta (50 and 500 pg/ml) while addition of the active form of the hormone could modulate both CYP24 and osteopontin gene expression. The 1alpha-OHase gene was also expressed in ectopic endometrium and its levels were increased in proliferative phase cultures derived from patients with endometriosis. Human cycling endometrium may be included among the extrarenal sites able to synthesize vitamin D. The IL-1beta-mediated induction of 1alpha-OHase gene and the hormonal modulation of osteopontin support a role for the hormone in the immunological mechanisms underlying uterine function. Abnormalities of this system are present in endometriosis.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

[Progestogens and estroprogestins in the treatment of pelvic pain associated with endometriosis].

We performed a MEDLINE and EMBASE search to identify all studies published in the English language literature on the use of progestogens for the treatment of endometriosis. The aim of our review was to clarify the biological rationale for treatment and define the drugs that can be used. It has been demonstrated that progestogens may prevent implantation and growth of regurgitated endometrium by inhibiting the expression of matrix metalloproteinases and angiogenesis, and they have several anti-inflammatory in vitro and in vivo effects that may reduce the inflammatory state generated by the metabolic activity of the ectopic endometrium. Oral contraceptives increase the abnormally low apoptotic activity of the endometrium of patients with endometriosis. Moreover, anovulation, decidualization, amenorrhoea and the establishment of a steady estrogen-progestogen milieu contribute to disease quiescence. Progestogens are able to control pain symptoms in approximately three out of four women with endometriosi. Different compounds can be administered by the oral, intramuscular, subcutaneous, intravaginal or intrauterine route, each with specific advantages or disadvantages. Medical treatment plays a role in the therapeutic strategy only if administered over a prolonged period of time. Given their good tolerability, minor metabolic effects and low cost, progestogens must therefore be considered drugs of choice and are currently the only safe and economic alternative to surgery. However, their contraceptive effectiveness limits their use to women who do not wish to have children in the short-term.

Administration, Oral↗

Genetics of endometriosis.

UNLABELLED: Endometriosis is a multifactorial disease that can affect up to 10-15% of women in their reproductive age. Epidemiological studies indicate that it is a polygenic disorder with recurrence risks in first-degree relatives of about 5-7%. Thus, the present aim of different research groups is to identify genetic variations in obvious candidate gene that could be associated with an increased susceptibility to endometriosis. The great advancement in molecular biology techniques make this task certainly possible, although particular attention needs to be paid to the study design in order to achieve reliable RESULTS: The data obtained by such studies will allow to expand our knowledge on the pathogenesis of the disease and, more importantly, to develop individualized therapies and prevention strategies to apply at high-risk populations.

Alleles↗

Analysis of the codon 72 polymorphism of the TP53 gene in patients with endometriosis.

Endometriosis is a benign gynaecologic disease that is associated with a certain risk for malignant degeneration. The disease has a genetic background, but the locations of possible genomic aberrations are still poorly clarified. In this context, the proline form of TP53 codon 72 polymorphism has been recently associated with the risk of developing endometriosis. In this case-control study, we aimed to investigate further the potential association between endometriosis and this polymorphism in order to evaluate whether this genetic variant may influence the susceptibility to the disease. Genomic DNA was obtained from a consecutive series of 303 Italian Caucasian women of reproductive age who underwent laparoscopy for benign gynaecological pathologies. Endometriosis was defined according to the criteria of Holt and Weiss [Holt V and Weiss NS (2000) Recommendations for the design of epidemiologic studies of endometriosis. Epidemiol 11,654-659] for the definite disease. Subjects of similar age without laparoscopic evidence of the disease served as control group. Molecular analysis of TP53 codon 72 polymorphism was performed by PCR amplification. Endometriosis was documented in 151 women. We found no statistically significant difference in the distribution of TP53 codon 72 polymorphism genotypes between patients with and without endometriosis. The respective proportions of arginine homozygotes, heterozygotes and proline homozygotes were 55.6, 39.7 and 4.6% in the group with endometriosis and 59.9, 30.9 and 9.2% in the control group. Moreover, no statistically significant association was demonstrated between TP53 codon 72 polymorphism and the various clinical manifestations of the disease, although a non-significant tendency towards an increased frequency of the proline allele was observed in association with specific manifestations of the disease reflecting a more severe form. Our results suggest that the TP53 codon 72 polymorphism does not confer genetic susceptibility to endometriosis in the Italian population. However, a possible susceptibility role of this polymorphism in endometriosis development towards very severe forms cannot be ruled out.

Adult↗

Use of the concomitant serum dosage of CA 125, CA 19-9 and interleukin-6 to detect the presence of endometriosis. Results from a series of reproductive age women undergoing laparoscopic surgery for benign gynaecological conditions.

BACKGROUND: Recent studies have proposed the measurement of CA 19-9 and IL-6 as an alternative to CA 125 as markers for endometriosis. This study was performed in order to verify the clinical value of serum CA 125, CA 19-9 and IL-6 levels, either by themselves or combined, in the detection of the disease. METHODS: In a prospective cohort study, serum concentrations of CA 125, CA 19-9 and IL-6 were measured in a consecutive series of 80 women of reproductive age who underwent laparoscopy for benign gynaecological pathologies. RESULTS: Endometriosis was documented in 45 women (stage I-II in 14 cases and stage III-IV in 31 cases). Patients with endometriosis had significantly higher levels of CA 125 than controls [23.4 IU/ml (13.3-37.6) versus 11.4 IU/ml (9.1-18.5), P < 0.001)]. Conversely, women with and without the disease were shown to have similar levels of both IL-6 pg/ml [0.6 (undetectable-1.4) versus 1.0 pg/ml (0.4-1.9), P = 0.09] and CA 19-9 [9.8 IU/ml (4.5-20.8) versus 7.4 IU/ml (2.8-11.5), P = 0.11]. The area under the receiver operating characteristics curve resulted in a statistically significant difference from the null hypothesis only for CA 125 (P < 0.001). Sensitivity and specificity of CA 125 were 27 and 97% respectively and were higher than those related to CA 19-9 and IL-6. Concomitant use of the three dosages led to a sensitivity and a specificity of 42 and 71% respectively. CONCLUSIONS: The concomitant dosage of CA 125, CA 19-9 and IL-6 does not add significant information in respect to the CA 125 test alone in diagnosing either early or advanced stages of endometriosis.

Adult↗

Lopinavir/ritonavir treatment in HIV antiretroviral-experienced patients: evaluation of risk factors for liver enzyme elevation.

OBJECTIVES: To evaluate the risk factors for lopinavir/ritonavir (LPV/r)-related liver enzyme elevation (LEE) in HIV antiretroviral-experienced patients. METHODS: An open prospective observational study was carried out to analyse the incidence and time of LEE development during LPV/r treatment, and to determine whether LEE development was correlated with epidemiological, clinical and biochemical data, immune and virological profiles, concomitant hepatic diseases, antiretroviral therapy, or histological and ultrasonography liver examination results. A diagnosis of LEE was considered when LEE symptoms occurred after LPV/r introduction and was confirmed by a second control within 2 weeks. RESULTS: A total of 782 HIV-positive outpatients have been enrolled in six different Infectious Diseases Departments in Northern Italy since August 2000. Of these patients, 71 (9.1%) developed LEE within 115+/-85 days (mean+/-standard deviation); 13 of these subjects discontinued LPV/r and four were hospitalized. Of the patients with LEE, 74.6% and 25.4% had grade 2 and > or =3 toxicity, respectively. No correlation between LEE and sex, baseline CD4 cell count, viral load, HIV stage, triglyceride values, histological and ultrasonography liver examination results, nevirapine use, or increase in CD4 cell count was observed. Higher baseline alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) values (P < 0.0001 and P=0.004, respectively), younger age (P=0.008), previous hepatitis B virus (HBV) infection (P=0.012), efavirenz use (P=0.04), and hepatitis C virus (HCV) and/or HBV coinfection (P < 0.0001, relative risk 4.78) were significantly related to LEE. No correlations between LEE and the same risk factors as investigated in the whole study population were found in subgroups of patients with HCV and/or HBV infection. CONCLUSIONS: HCV and HBV testing and measurement of baseline ALT values are essential for screening subjects at risk of LEE before starting LPV/r. Strict monitoring of clinical and biochemical parameters should be performed in these patients.

Adult↗

Maternal-conceptus cross talk--a review.

The implantation process requires a functionally normal conceptus and a receptive endometrium, but also a communication link between them. This paracrine dialogue involves not only gonadal steroids but also a variety of other biologic molecules secreted by the conceptus and the reproductive tissues themselves in a communicative, interconnected network. The factors facilitating this dialogue includes chemokines, cytokines, adhesion molecules, growth factors. Recently, the soluble form of HLA-G and the vitamin D system have also been proposed as components of this cross-talk. Inherent among the factors involved is the fact that their effects are redundant and pleiotropic. Normal implantation and placentation are critical for a successful pregnancy. Therefore, a better understanding of the molecular mechanisms responsible for these processes will lead to the development of new regulating agents with novel diagnostic, biological and therapeutic potential for both facilitating and hindering a normal reproductive function.

Adult↗

Discontinuing combination antiretroviral therapy during the first trimester of pregnancy: insights from plasma human immunodeficiency virus-1 RNA viral load and CD4 cell count.

OBJECTIVE: Options for human immunodeficiency virus-1-infected women who are already receiving antiretroviral medications when they become pregnant include the continuation or discontinuation of the therapy during the first trimester. These two strategies are compared in terms of plasma human immunodeficiency virus viral load and CD4 cell count. STUDY DESIGN: Seventy women who attended the II Department of Obstetrics and Gynecology were identified. Four different periods for laboratory evaluations were decided: presuspension, suspension, second trimester, and third trimester. RESULTS: Thirty-two women (46%) discontinued antiretroviral therapy; 38 women (54%) did not. Whereas plasma HIV virus viral load and CD4 cell count did not significantly vary during pregnancy in patients who did not interrupt the therapy, these two variables were influenced significantly by the discontinuation of treatment (P<.001 for both). Human immunodeficiency virus viral load increased during the suspension period and regressed promptly to basal levels as soon as the therapy was reintroduced. A transitory decrease in CD4 cell count was also documented, but the recovery tended to be slower. CONCLUSION: The suspension of combination antiretroviral therapy during the first trimester of pregnancy transiently corresponds to an increase in human immunodeficiency virus viral load and a decline of CD4 cell count.

Acquired Immunodeficiency Syndrome↗

Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms in endometriosis.

Endometriosis is a gynaecological disease with a certain genetic background, but the locations of possible genomic aberrations are still poorly clarified. Intercellular adhesion molecule-1 (ICAM-1), which is a surface glycoprotein that promotes adhesion in immunological and inflammatory reactions, seems to play a role in this condition. The aim of this study was to examine the potential associations of ICAM-1 gene polymorphisms with endometriosis and its severity. Specifically, we have studied two polymorphic sites located in codons 241 (G/R241) and 469 (E/K469) of the ICAM-1 gene. Three hundred and sixty-three Italian Caucasian women of reproductive age who underwent laparoscopy for benign pelvic conditions were enrolled in the study. Endometriosis was documented and staged in 188 women while 175 subjects, in whom endometriosis was laparoscopically ruled out, served as the control group. The frequency of the R241 allele was only marginally higher in endometriosis patients than in controls [5.8 versus 2.9%, P = 0.05; odds ratio (OR), 2.1; 95% confidence interval (CI), 1-4.5]. However, a strikingly high frequency of this allele was found in patients with Stage IV endometriosis versus controls (8.6 versus 2.8%, P = 0.008; OR, 3.2; 95% CI, 1.3-7.9). In contrast, the allele and genotype frequencies of the E/K469 polymorphism did not differ significantly between endometriosis and control groups. While the functional correlate of the G/R241 polymorphism remains unclear, this finding indicates that a genetic polymorphism in the ICAM-1 gene domain may contribute to the susceptibility to endometriosis.

Adult↗

Different basic fibroblast growth factor and fibroblast growth factor-antisense expression in eutopic endometrial stromal cells derived from women with and without endometriosis.

In all species studied, the basic fibroblast growth factor (bFGF) gene is transcribed into multiple mRNAs, one of which is an antisense RNA (1B FGF-AS) probably involved in regulating the stability of the sense transcript. In this study we investigated whether the regulatory mechanisms of bFGF expression might be altered in endometrial stromal cells derived from women with endometriosis. bFGF and 1B FGF-AS mRNA levels were quantified in primary cultures of eutopic endometrial stromal cells derived from 29 women without endometriosis and 24 patients affected by the disease. When the data were analyzed according to the phase of the menstrual cycle, endometrial stromal cells derived from patients in the late proliferative phase showed significantly higher bFGF mRNA values and significantly lower 1B FGF-AS mRNA levels compared with control samples. Furthermore, the mean bFGF/1B FGF-AS mRNA ratio was significantly higher in endometrial stromal cells derived from patients compared with that in controls (mean +/- SEM, 2.31 +/- 0,55 and 0.77 +/- 0.14, respectively; P = 0.009). Moreover, for bFGF expression the differences existing at the mRNA level were maintained at the protein level. These findings support the hypothesis that 1B FGF-AS mRNA could regulate the expression of the sense transcript and suggest that in endometrial cells derived from patients, the presence of higher bFGF levels could improve their ability to proliferate at the ectopic site.

Base Sequence↗

[The therapy of endometriosis. New prospects].

Surgery is still the first line of therapy for endometriosis. At present, medical therapy is mostly indicated for treatment and prevention of recurrences. Current pharmacological regimens induce a hypoestrogenic state; this effect tends, on one hand, to inhibit the growth of endometriotic implants while, on the other hand, it significantly interferes with the integrity of the hypothalamus-pituitary-ovarian axis. The aim of this study is to review current knowledge on the new experimental therapeutic approaches to the disease. English articles on this topic have been searched by Medline. A particular attention has been paid to experimental therapeutic interventions supported by in vivo results. Three different novel strategies have been identified: 1) To act on estrogenic dependence of endometriosis using new drugs such as aromatase inhibitors and raloxifene. These drugs may have the advantage to act more specifically on the disease. 2) To treat the disease with immuno-modulators and anti-inflammatory drugs. These compounds may be helpful in both limiting the growth of endometriotic implants and in controlling the symptoms of the disease. 3) To prevent adhesion reformation after surgical lysis. Adhesions are an important hallmark of endometriosis which cannot be adequately eliminated by surgery. The use of barrier and fluid agents after surgical lysis seems to be effective in this regard. Results from studies aimed to investigate the effectiveness of these approaches are appealing. However, controlled clinical trials are now required to appropriately determine their real benefits and their specific indications.

Adjuvants, Immunologic↗

Use of knockout transgenic mice in the study of endometriosis: insights from mice lacking beta(2)-microglobulin and interleukin-12p40.

OBJECTIVE: To test the possibility of using transgenic knockout mice in the study of endometriosis and to investigate specific immunologic aspects of the disease. DESIGN: Experimental blinded study. SETTING: Academic research center. ANIMAL(S): Thirty-two mice with experimentally induced endometriosis. INTERVENTION(S): Endometriosis was induced in 8 beta(2)-microglobulin-deficient BALB/c mice and 7 wild-type BALB/c controls. Similarly, endometriosis was induced in 8 interleukin-12-deficient C57BL/6 mice and in 9 wild-type C57BL/6 controls. MAIN OUTCOME MEASURE(S): Weight and surface area of endometriotic lesions. RESULT(S): Total weight and surface area of endometriotic lesions was markedly lower in beta(2)-microglobulin-deficient BALB/c mice than in wild-type BALB/c controls. A slight but statistically insignificant increase in total weight and surface area of lesions was observed in interleukin-12-deficient C57BL/6 mice compared to wild-type C57BL/6 controls. CONCLUSION(S): Knockout transgenic mice can be used successfully for the study of endometriosis; however, in these animals, the redundancy of the immunologic cytokine-mediated regulatory mechanisms may lead to compensation from the remaining genome. Results from beta(2)-microglobulin-deficient mice support the critical role of the immune system in the pathogenesis of the disease.

Animals↗

Effects of androgen supplementation of hormone replacement therapy on the vascular reactivity of cerebral arteries.

OBJECTIVE: To determine the effect of the androgen supplementation of hormone replacement therapy (HRT) on the vascular reactivity of cerebral arteries. DESIGN: Open randomized study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Forty postmenopausal women who were treated with sequential HRT (transdermal E2 50 microg/d + medroxyprogesterone acetate 10 mg/d for 12 days every other month) for > or =1 year and < or =5 years. INTERVENTION(S): Testosterone undecanoate (40 mg/d, p.o.) was randomly administered to 20 patients during ongoing HRT; the other 20 served as controls. Doppler evaluations of the internal carotid and middle cerebral arteries were performed together with lipid levels assessments. A visual analogue scale (VAS) was used to evaluate various parameters relating to sexual life and well-being. MAIN OUTCOME MEASURE(S): Pulsatility index (PI) of the arteries, VAS assessment of psychophysical well-being. RESULT(S): The administration of testosterone undecanoate during HRT induced an increase in the PI of the middle cerebral artery and a reduction of high-density lipoprotein cholesterol. Sexual desire and satisfaction were greatly improved. CONCLUSION(S): In postmenopausal women, androgen supplementation during HRT can partially counteract the beneficial effects of estrogens on cerebral vascular reactivity and lipid profiles, but sexual desire and satisfaction are greatly improved.

Administration, Cutaneous↗

Induction of endometriosis in the mouse inhibits spleen leukocyte function.

BACKGROUND: It is still unclear whether the immunologic perturbation observed in women with endometriosis represents an intrinsic defect of the immune system or it is consequent to the presence of endometrium in ectopic sites. The present study was aimed to evaluate the immunoregulatory properties of ectopic endometrial implants in a model of experimental endometriosis in mice. METHODS: Endometriosis was induced in n=10 mice by inoculating endometrial fragments obtained from syngenic donor mice into the peritoneal space. Twelve mice were similarly treated but were not inoculated with endometrium and were used as control mice. At an explorative laparotomy performed in all the animals after three weeks, the extent of peritoneal lesions, when present, was evaluated by weight assessment and surface area measurement. In both mice that were inoculated with endometrium and control animals, spleens were removed. The effect of endometriosis induction on concanavalin A-induced spleenocyte proliferation was investigated. RESULTS: A significant inhibition of spleenocyte growth was demonstrated in mice in which endometriosis was induced (36156+/-3061 cpm) compared to control animals (47172+/-3210 cpm; p<0.05). Moreover, a significant inverse correlation was found between spleenocyte proliferation and weight and surface area of the peritoneal endometriotic lesions (r=0.76; p<0.02 and r=0.75; p<0.02, respectively). CONCLUSION: These findings suggest that the presence of ectopic endometrial implants within the peritoneal cavity leads to substantial changes of the immune response in vivo. These changes may have significant implications for the understanding of the etiopathogenesis of endometriosis.

Animals↗

Suppression of natural killer cell function and production of soluble ICAM-1: endometrial stroma versus melanoma.

PROBLEM: It has been suggested that specific mechanisms commonly used by different cellular systems to evade immunologic recognition are involved in the development of endometriosis. To gain insight into this aspect, we looked at the relationship between two of these mechanisms in endometrial stroma and the melanoma system for which the ability to create an environment of immune privilege has been well established. METHOD OF STUDY: Media conditioned by endometrial stromal cultures and malignant melanoma A375 were examined to test their effects on peripheral blood mononuclear cell-mediated cytotoxicity directed against K562 target. Moreover, these media were tested for the concentration of the soluble form of intercellular adhesion molecule-1 (sICAM-1), which has been suggested as a marker for spreading potential. RESULTS: Media conditioned by endometrial stromal cultures exerted a significant suppressive effect on cell cytotoxicity when compared with those derived from malignant melanoma Moreover, the constitutive release of sICAM-1 was significantly higher in supernatants from endometrial stromal than in melanoma cells. CONCLUSIONS: These results indicate that two specific properties suggested to be involved in the ability of tumor cells to evade the immune system are more pronounced in the endometrium than in a malignant melanoma. Since the properties evaluated have been previously demonstrated to be even more notable in endometrial samples derived from endometriosis patients, a role of these mechanisms in the development of the disease may be hypothesized.

Cytotoxicity, Immunologic↗