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PubMed1997

Fibroblast growth factor receptor-1 is a critical component for endometrial remodeling: localization and expression of basic fibroblast growth factor and FGF-R1 in human endometrium during the menstrual cycle and decreased FGF-R1 expression in menorrhagia.

Angiogenic growth factors play a critical role in the cyclic growth and vascularization of normal endometrium. Herein, we report the expression and localization of both basic fibroblast growth factor (FGF-2) and its receptor (FGF-R1; flg) in human endometrium and demonstrate the markedly decreased FGF-R1 levels in menorrhagia. In situ hybridization using [35S]-labeled riboprobe demonstrated distinct autoradiographic signals for FGF-2 mRNA in glandular epithelial and stromal cells in endometrium throughout the menstrual cycle, with the strongest hybridization signal in stromal cells of the proliferative endometrium relative to that of the secretory endometrium. Moreover, RNAse protection assay revealed that the mRNA encoding FGF-2 and FGF-R1 was significantly higher in proliferative than in secretory endometrium (p < 0.05, p < 0.01). Immunohistochemistry using anti-flg antibody showed that the intensity of FGF-R1 staining was markedly diminished in the stromal cells of secretory endometrium, which corresponded with the reduced FGF-2 mRNA expression. In contrast, the endometrial glandular epithelial cells showed intense localization of FGF-R1 protein throughout the menstrual cycle, which paralleled FGF-2 mRNA expression. Colocalization of FGF-2 and FGF-R1 in stroma and stimulation of DNA synthesis and phospholipase C activation by FGF-2 in these cells demonstrates that FGF-2 acts in an autocrine manner in endometrial stroma. Western immunoblotting showed that FGF-R1 immunoprotein was markedly reduced or absent in women with menorrhagia throughout the cycle relative to that of normal cycling women, suggesting that FGF-R1 is critical for endometrial "maturation" and regeneration of the normal endometrium following menstruation.

Adult↗
PubMed1998

Endometrial brush cytology of advanced postmenopausal endometrium: does endometrial intraepithelial neoplasia exist in the absence of hyperplasia?

Postmenopausal uterine bleeding is an indication to sample the endometrium for diagnostic purposes. The endometrial brush cytologies of 20 advanced postmenopausal women collected at the time of hysterectomy in order to benchmark the expected morphology of postmenopausal endometrial brushings were reviewed. No women had symptoms or gross findings of primary endomyometrial disease. Endometrium was collected at the surgical pathology laboratory using the Tao Brush and CytoRich Fixative System. After formalin fixation of the uterus, the entire endometrium was embedded for routine histology. Sixteen endometrial brushings and matched endometrial sections showed endometrial atrophy, one brushing showed many ciliated epithelial cells, and three brushings showed focal (less than 10%) epithelial-cell atypia. In two atypias, abnormal endometrial epithelial-cell sheets contained enlarged, clear nuclei with nuclear notches and grooves resembling papillary thyroid cancer. One case showed no histological counterpart to this finding. The other case showed thickening of the pericornual fundic endometrium with cystic glands. The third case with epithelial atypia showed abnormal endometrial-cell sheets with nuclei resembling atypical hyperplasia or type I endometrial adenocarcinoma; corresponding endometrial tissue sections showed rare, irregular glands and back-to-back gland clusters with equivalent nuclear features. Atypical epithelium may be found in atrophic uteri in the absence of gross endometrial thickening. This may be a common event related either to de novo intraepithelial dysplasia in a noncycling endometrium or to hyperplasia that has partly regressed with estradiol withdrawal. This study shows that, in addition to endometrial intraepithelial carcinoma (EIC), isolated atypical glands with morphological and immunohistochemical features of atypical hyperplasia or type I endometrial adenocarcinoma may be found in grossly normal advanced postmenopausal endometrium of asymptomatic patients. This atypical epithelium is readily apparent in endometrial brush preparations, but requires serial sectioning of the endometrium to be demonstrated histologically. We have not established the natural history of this lesion, and in the absence of EIC or gross endometrial thickening indicative of atypical hyperplasia, we do not know whether this degree of epithelial atypia should be an indication for hysterectomy.

Adenocarcinoma↗
PubMed2006

Gray-scale ultrasound morphology in the presence or absence of intrauterine fluid and vascularity as assessed by color Doppler for discrimination between benign and malignant endometrium in women with postmenopausal bleeding.

OBJECTIVE: To determine if gray-scale ultrasound morphology in the presence or absence of intrauterine fluid and endometrial vascular morphology as assessed by color Doppler ultrasonography can discriminate between benign and malignant endometrium in women with postmenopausal bleeding. METHODS: In a prospective study 95 consecutive women with postmenopausal bleeding and endometrial thickness > or = 4.5 mm as measured by transvaginal ultrasound were included. Gray-scale and color Doppler ultrasound examination of the endometrium was performed. The ultrasound examiner characterized the morphology of the endometrium before and during saline infusion and assessed the endometrial vascular tree using a predetermined classification protocol without suggesting a diagnosis. A histopathological diagnosis was obtained by operative hysteroscopy, dilatation and curettage or hysterectomy. RESULTS: There were no statistically significant differences in ultrasound findings between benign and malignant endometria of uterine cavities without fluid. Heterogeneous echogenicity, irregular surface, and both heterogeneous echogenicity and irregular surface of a focal lesion (or of the endometrium in the absence of focal lesions) in a uterine cavity filled with fluid (spontaneous or infused) were significantly more common in malignant than in benign endometrium. The sensitivity, false positive rate, positive and negative likelihood ratios of these findings were as follows: heterogeneous echogenicity, 80%, 29%, 2.74, 0.28, P = 0.003; irregular surface, 89%, 33%, 2.70, 0.17, P = 0.002; and both, 78%, 12%, 6.59, 0.25, P < 0.001. Two or more vessels were found in 67% (8/12) of the malignant endometria vs. 51% (40/79) of the benign endometria (non-significant difference). Vascular branching tended to be more common in malignant endometria (10/11; 91%) than in benign endometria (39/61; 64%), P = 0.09. CONCLUSION: Heterogeneous echogenicity and an irregular surface of a focal lesion or of the endometrium in a fluid-filled uterine cavity are useful ultrasound criteria for predicting endometrial malignancy. Assessment of vascular morphology using color Doppler ultrasound is of limited--if any--value for discrimination between benign and malignant endometrium.

Adult↗
PubMed1985

Pregnancy-related changes in the human endometrium revealed by lectin histochemistry.

The binding of 22 fluorescein isothiocyanate (FITC) conjugated lectins to human proliferative phase and pregnant endometrium was studied histochemically. Only the lectin from Bauhinia purpurea (BPA) reacted exclusively with the epithelial cells. All the others reacted to a certain extent with glandular and/or stromal cells. Lectins from soybean (SBA), and Vicia villosa seeds (VVA) reacted with endometrial glands of pregnancy but not with the glands of the proliferative endometrium. In the proliferative endometrium SBA reacted only with cells of the surface endometrium. Lectin from peanuts (PNA) reacted only with some glands in the proliferative endometrium but was unreactive with others. In pregnant endometrium PNA reacted with all glands. Lectins from lentils (LCA) and red kidney beans (PHA-E and PHA-L) reacted with endometrial glands of the proliferative phase but not with the glands from pregnant endometrium. We thus show that FITC labeled lectins define specific carbohydrate moieties selectively expressed on either proliferative phase or pregnant endometrial glands.

Endometrium↗
PubMed1993

The number of proliferating cell nuclear antigen positive cells in endometriotic lesions differs from that in the endometrium. Analysis of PCNA positive cells during the menstrual cycle and in post-menopause.

Immunohistochemical expression of proliferating cell nuclear antigen (PCNA) was studied in the endometrium and in endometriotic lesions during the menstrual cycle and in post-menopausal patients. During the menstrual cycle, in the basal layer of the endometrium, an increase in the number of positive indices (PI) of PCNA was observed in epithelial cells from the menstrual phase. It reached a maximum in the proliferative phase and decreased in the secretory phase. However, no change was observed in the stromal cells of the basal layer. In the functional layer of the endometrium, the PI of the epithelial cells showed a high peak in the late proliferative phase, decreased sharply in the secretory phase and remained unchanged thereafter. The PI of the stromal cells in the functional layer showed two peaks, one in the late proliferative and the other in the mid and late secretory phase. In the endometriotic lesions, except for the proliferative phase, the number of PI was significantly higher than that of the corresponding endometrium and no significant changes were observed during the menstrual cycle. In post-menopausal endometriotic lesions, the number of PI was also higher than that of the corresponding endometrium. Thus the numbers of PI differed between the endometrium and endometriotic lesions in the same patients. These results imply that the endometriotic lesions are constantly more proliferative than the endometrium irrespective of the hormonal milieu during both the menstrual cycle and in a post-menopausal environment.

Adult↗
PubMed2005

Immunohistochemical analysis of c-myc, c-jun and estrogen receptor in normal, hyperplastic and neoplastic endometrium.

To evaluate the role of c-jun and c-myc proto-oncogenes in normal, hyperplastic and neoplastic endometrium in relation to estrogen receptor (ER) status and to investigate whether these genes can be related to other histopathological features of endometrial carcinoma, 32 endometrial carcinomas, 38 endometrial hyperplasias and 22 cyclic endometria (10 proliferative and 12 secretory) were evaluated histologically. Endometrial hyperplasia cases were classified as simple and complex hyperplasia without atypia, and atypical hyperplasia. Endometrial carcinoma cases were subtyped according to the International Society of Gynecological Pathologists. Modified FIGO system was used for both grading and staging. Immunohistochemical examination was performed using antibodies to ER-alpha, c-myc and c-jun with streptavidin-biotin-peroxidase technique. The mean percentage of ER-alpha positive cells changed cyclically during the menstrual cycle, and it was the highest (96%) and the lowest (31.6%) in proliferative and carcinomatous endometrium, respectively. There was a statistically significant difference between proliferative and secretory phases and proliferative and carcinomatous endometrium in relation to ER-alpha staining (p<0.05). There was also a statistically significant difference with respect to ERalpha reactivity between secretory phase and each hyperplastic group, as well as between the carcinoma group and each hyperplastic group (p<0.05). Although not significant, the mean percentage of c-myc expressing cells in the carcinoma group was higher (15.3%) than that of proliferative phase and hyperplastic groups. The mean percentage of c-jun positive cells in proliferative endometrium was slightly higher than in secretory endometrium, and it was the highest in atypical hyperplastic endometrium (28.3%), but there was no statistically significant difference between the groups. In carcinoma cases, a positive correlation was observed between c-jun positivity and tumor grade (p=0.027, r=0.3908), but such a correlation with c-myc was not found. A positive correlation was detected between ER-alpha and c-myc expression (p=0.038, r=0.3686). A progressive loss of ER seems to be correlated with increasing malignant transformation. C-myc expression might play a role in the development of endometrial carcinoma via ER. The association between c-jun and ER appears to be lost in endometrial carcinoma. The relationship between c-myc, c-jun and ER appears to be altered in endometrial carcinoma compared to that of menstrual endometrium.

Adult↗
PubMed2005

Oestrogen-modulated gene expression in the human endometrium.

To identify key regulatory mechanisms in the growth and development of the human endometrium, microarray analysis was performed on uncultured human endometrium collected during menstruation (M) and the late-proliferative (LATE-P)-phase of the menstrual cycle, as well as after 24 h incubation in the presence of oestradiol (17beta-E2). We demonstrate the expression of novel gene transcripts in the human endometrium. i.e. mucin-9, novel oestrogen-responsive gene transcripts, i.e. gelsolin and flotillin-1, and genes known to be expressed in human endometrium but not yet shown to be oestrogen responsive, i.e. connexin-37 and TFF1/pS2. Genes reported to be expressed during the implantation window and implicated in progesterone action, i.e. secretoglobin family 2A, member 2 (mammaglobin) and homeobox-containing proteins, were up-regulated in uncultured LATE-P-phase endometrium compared to M-phase endometrium. Some gene transcripts are regulated directly by 17beta-E2 alone, others are influenced by the in vivo environment as well. These observations emphasise that the regulation of endometrium maturation by oestrogen entails more then just stimulation of cell proliferation.

Adult↗
PubMed1985

Metabolism of adrenal androgens by human endometrium and adrenal cortex.

The enzyme 17 beta-hydroxysteroid dehydrogenase (17OHSD) was studied in human endometrium and adrenal cortex with respect to the metabolism of 5-androstene-3 beta,17 beta-diol (androstenediol) and dehydroepiandrosterone (DHA). The aim was to provide further information concerning the origin and biological significance of these androgens in endometrium, particularly the increased concentrations of the secretory phase and to compare the characteristics of the enzyme in the two tissues. In both endometrium and adrenal cortex the metabolism of androstenediol to DHA was linear with time and increasing enzyme concentration. The preferred cofactor was NAD and the apparent Km values were 3.4 +/- 0.2 (SD) microM (n = 3) for endometrium and 30.5 +/- 6.1 microM (n = 3) for adrenal cortex. In endometrium DHA was not metabolised to androstenediol in the presence of either NADH or NADPH whereas in the adrenal cortex both cofactors were utilised. However, the concentration of NADH required to achieve maximum enzyme activity was 10-fold higher (1 mM) than for NADPH (0.1 mM) and maximum activity with NADH was only 30% of that using NADPH. The apparent Km was 125 microM DHA (n = 2). The study indicates that androstenediol in endometrium does not arise from DHA metabolism but that its presence could be due to a binding protein particularly during the secretory phase. Our findings also suggest that the enzyme of endometrium differs from that of the adrenal cortex and that the kinetic properties may be related to the physiological requirements of the two tissues.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Cyclic expression of endothelial nitric oxide synthase mRNA in the epithelial glands of human endometrium.

OBJECTIVES: Nitric oxide synthase (NOS), responsible for the synthesis of nitric oxide (NO), is the key enzyme that regulates the NO-mediated biologic functions in various types of tissue. We believed that NO may be involved in regulating the development of the microvascular system and vascular tone in human endometrium. However, the biology of NOS in this system remains poorly understood. To determine the paracrine action of NOS derived from endometrial cells on vascular blood flow, the first task is to identify NOS in endometrial cells. This study was undertaken to examine whether human endometrial cells would express endothelial or inducible NOS (eNOS or iNOS). In addition, we examined the cell-specific expression of eNOS. METHODS: Beta nicotinamide adenine dinucleotide reduced from (NADPH)-diaphorase histochemistry assay was carried out in human endometrial specimens (n = 4). Nitric oxide synthase mRNA expression was studied in intact tissue (n = 4), isolated epithelial glands (n = 25), and stromal cells (n = 10). Northern blot and solution hybridization/ribonuclease protection assay with specific RNA probes transcribed from human eNOS and iNOS cDNA were used to identify NOS mRNAs. RESULTS: NADPH-diaphorase histochemistry selectively labeled epithelial glands in the late secretory phase. Northern blot analysis revealed that glandular cells expressed a single size of eNOS mRNA (4.5 kb) but no detectable iNOS. Endothelial NOS mRNA was expressed in epithelial glands, but it was not detectable in stromal cells. The relative amount of eNOS in epithelial glands isolated from specimens (n = 23) at various stages of menstrual cycle were analyzed using a solution hybridization assay. The levels of eNOS mRNA varied among specimens. Epithelial glands from early secretory endometrium showed greater expression of eNOS mRNA. The highest eNOS expression was found in the glands of late secretory endometrium. In contrast, iNOS was detected only in the epithelial glands of a menstrual endometrium. CONCLUSION: This study demonstrated that NADPH-diaphorase activity is highly concentrated in the epithelial glands of late secretory endometrium. Expression of eNOS mRNA is enhanced in the glands of early secretory endometrium. The strongest expression resides in the epithelial glands of late secretory endometrium. This observation suggests that regulation of eNOS may be a physiologic response to steroid hormones and locally produced peptide hormones in the endometrial environment. It also suggests that NO may play a role in the onset of menses.

Cells, Cultured↗
PubMed2004

Expression of HOXA11 gene in human endometrium.

OBJECTIVE: This study was conducted to examine HOXA11 gene expression in the human endometrium during normal menstrual cycle. STUDY DESIGN: Expression of HOXA11 was examined in the endometrium by in situ hybridization and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: In the proliferative and early secretory endometrium, both glandular and stromal cells expressed HOXA11 after hybridization. It is interesting to note that the expression in glandular epithelium was dramatically decreased or disappeared in the midsecretory phase at the time of implantation. This expression patterning was kept in the late secretory endometrium and decidua of early pregnancy, whereas in stromal cells, a high-level expression was found and no variations were detected during the menstrual cycle. Semiquantitative RT-PCR analysis demonstrated that total HOXA11 messenger RNA levels were markedly increased in the midsecreatory endometrium. CONCLUSION: This study reveals a novel expression pattern for HOXA11 gene in human endometrium and the downregulation of HOXA11 in glandular epithelium may be necessary for the differentiation and receptivity of endometrium.

Endometrium↗
PubMed2006

Oral contraceptives maintain a very thin endometrium before operative hysteroscopy.

OBJECTIVE: To show that early follicular-phase administration of an oral contraceptive pill (OC) consistently provides a thin endometrium, as determined by transvaginal ultrasound. This is an ideal condition when performing operative hysteroscopy. DESIGN: Retrospective chart review of patients who have undergone ultrasound evaluation of the endometrial thickness under different hormonal conditions. Endometrial measurement was obtained during menstruation, in the late follicular phase, and in the luteal phase in 20 patients. In another group of 100 patients, endometrial measurement was made on the 18th day of OC administration, initiated during menses. SETTING: A reproductive endocrinology unit in a university-affiliated medical center. PATIENT(S): Patients undergoing treatment for subfertility of various etiologies. INTERVENTION(S): Transvaginal ultrasound measurements of the endometrium. MAIN OUTCOME MEASURE(S): Endometrial thickness by transvaginal ultrasound. RESULT(S): Combination OCs started on menstrual days 1-3 maintain a uniformly thin endometrium, 4.1 +/- 1.6 mm (mean +/- SD), comparable to menstrual endometrium (3.7 +/- 1.5 mm). This was statistically thinner compared with endometrium observed in the late follicular phase (11 +/- 2.0 mm) or late luteal phase (12 +/- 2.3 mm). Transvaginal ultrasound measurements of the endometrium under different conditions were compared by the unpaired t-test. CONCLUSION(S): Oral contraceptives maintain a very thin, flat endometrium, such that lesions might be readily identified and treated during operative hysteroscopy procedures. Prevention of pregnancy and endometrial thinning with administration of OCs facilitates procedural scheduling for patients and surgeons.

Contraceptives, Oral↗
PubMed2006

The expression of fractalkine in the endometrium during the menstrual cycle.

OBJECTIVE: The objective of the study was to evaluate the presence of fractalkine in the endometrium of the uterus and the change of fractalkine protein levels during menstrual cycle. METHODS: Twelve samples of endometrium of the uterus were obtained from gynecological patients who underwent total hysterectomy. Western blotting, RT-PCR and immunohistochemistry were performed. RESULTS: Fractalkine protein was detected in the endometrium of the uterus. Positive staining was confirmed in the epithelial cells and grandular cells in the endometrium. Expression levels of fractalkine protein and mRNA in the endometrium during secretory phase were significantly higher than those during proliferative phase. Immunohistochemical analysis using an anti-CX3CR1 antibody demonstrated positive staining in the glandular cells of the endometrium of the uterus. CONCLUSION: Fractalkine was expressed in the endometrium and its production was up-regulated during secretory phase.

Adult↗
PubMed2006

Altered expression of interleukin-18 in the ectopic and eutopic endometrium of women with endometriosis.

OBJECTIVE: This study has investigated the expression of interleukin (IL)-18 in the eutopic and ectopic endometrium of women with endometriosis and the role of IL-18 on the pathogenesis of endometriosis. METHODS: Endometriotic tissue specimens and endometrium specimens were obtained from patients with endometriosis. IL-18 protein was determined by immunohistochemical analysis. Expression levels of IL-18 mRNA were analyzed by reverse transcriptase (RT)-PCR. RESULTS: IL-18 was detected in the glandular epithelial and stromal cells of eutopic and ectopic endometrium. RT-PCR analysis showed that endometrial IL-18 mRNA expression levels were significantly higher at the secretory phase than the proliferative phase in normal women, but not in patients with endometriosis. IL-18 mRNA expression levels were lower in the ectopic endometrium than in the eutopic endometrium of women with endometriosis. IL-18 mRNA levels in both ectopic and eutopic endometrium of patients with endometriosis were lower than in endometrium of women without endometriosis. CONCLUSION: Ectopic and eutopic endometrial IL-18 was down-regulated in women with endometriosis, suggesting that IL-18 might play a pathogenic role in the formation of endometriosis.

Adult↗
PubMed2005

Regulation of prostaglandin synthesis by interleukin-1alpha in bovine endometrium during the estrous cycle.

Interleukin (IL)-1 has been suggested to participate in regulation of many reproductive functions. To investigate the possible role of IL-1alpha as a local regulator in bovine endometrium, we determined the effects of IL-1alpha on prostaglandin (PG) E2 and PGF(2alpha) output by the bovine endometrium at different stages of the estrous cycle. The expressions of IL-1alpha and IL-1 receptor type 1 (IL-1RT1) mRNA in bovine endometrium were also studied. Bovine uteri were classified into six stages (estrus: day 0; early luteal: days 2-3; developing luteal: days 5-6; mid luteal: days 8-12; late luteal: days 15-17; and follicular: days 19-21). After 1h of pre-incubation, endometrial tissues (20-30mg) were exposed to 0 or 10ng/ml IL-1alpha for 4h. IL-1alpha significantly stimulated PGE2 output throughout the luteal stages, with the highest response during the mid luteal stage, while it did not stimulate PGE2 output during the estrus and the follicular stage. On the other hand, IL-1alpha significantly enhanced PGF(2alpha) output throughout the estrous cycle except in the endometrium from the mid luteal stage, with the highest response at the follicular stage (P<0.001). The treatment of endometrial tissue with IL-1alpha resulted in an increase of the PGE2:PGF(2alpha) ratio at the mid luteal stage, and in a decrease during the late luteal and follicular stages of the estrous cycle. A semiquantitative reverse transcription-polymerase chain reaction revealed that IL-1alpha and IL-1RT1 mRNA are expressed in the endometrium throughout the estrous cycle. IL-1alpha mRNA expression was greater in the early luteal stage than in the estrus, late luteal, and follicular stages (P<0.05). IL-1RT1 mRNA was greater in the late luteal stage than in the other stages (P<0.05). The overall results suggest that IL-1alpha is produced in bovine endometrium throughout the estrous cycle, and plays some roles not only in maintenance of CL, but also in luteolysis by regulating the local PGE2:PGF(2alpha) ratio in bovine endometrium during the estrous cycle.

Animals↗
PubMed1997

Bcl-2 and Fas expression in eutopic and ectopic human endometrium during the menstrual cycle in relation to endometrial cell apoptosis.

OBJECTIVE: Our purpose was to investigate Bcl-2 and Fas expression in human eutopic and ectopic endometrium during the menstrual cycle in relation to endometrial cell apoptosis. STUDY DESIGN: Eutopic and ectopic endometrial samples were obtained from 29 patients with endometriosis, and eutopic endometrial tissue samples were obtained from 9 patients with uterine myoma. Bcl-2 and Fas expression were examined by immunohistochemical staining with specific monoclonal antibodies; Bcl-2 expression in eutopic endometrium was also examined by Western blotting and apoptotic cells were detected by the labeling of deoxyribonucleic acid fragments. RESULTS: In eutopic endometrium Bcl-2 was strongly expressed during the proliferative phase. Endometrial glandular cells showed evidence of cyclic changes in Bcl-2 expression, but cyclic changes were not apparent in peritoneal and ovarian endometriotic tissue. Fas expression was observed on glandular cells but not on stromal cells, and no cyclic changes in expression occurred in either ectopic or eutopic endometrium. Apoptotic cells were observed primarily in the glandular cells of the basal layer in eutopic endometrium during the late secretory and menstrual phases. CONCLUSION: The current study indicated that there was no apparent correlation between Bcl-2 or Fas expression with endometrial cell apoptosis. The absence of cyclic changes in Bcl-2 expression in ectopic endometrium implied a difference in the mechanisms of proliferation or differentiation between eutopic and ectopic endometrium.

Adult↗
PubMed2000

Apoptosis and expression of Bcl-2 and Bax in eutopic endometrium from women with endometriosis.

OBJECTIVE: To evaluate and compare spontaneous apoptosis and Bcl-2 and Bax expression in eutopic endometrium from women with and without endometriosis. DESIGN: Apoptosis and Bcl-2 and Bax expression were examined in eutopic endometrium from women with and without endometriosis. SETTING: Instituto de Biología y Medicina Experimental-CONICET, Department of Gynecology and Department of Gynecological Pathology, Clínicas University Hospital, Buenos Aires, Argentina. PATIENT(S): Women with untreated endometriosis (n = 14) and controls (n = 16). INTERVENTION(S): Collection of endometrial samples during diagnostic or therapeutic laparoscopy. MAIN OUTCOME MEASURE(S): Apoptotic cells were detected with use of the dUTP nick-end labeling (TUNEL) assay; Bcl-2 and Bax expressions were assessed with use of immunohistochemical techniques. RESULT(S): Spontaneous apoptosis was significantly lower in eutopic endometrium from patients with endometriosis, compared with healthy controls (2.26 +/- 0.53 and 9.37 +/- 1.69 apoptotic cells/field, respectively) and was independent of cycle phase. An increased expression of Bcl-2 protein was found in proliferative eutopic endometrium from patients with endometriosis. Bax expression was absent in proliferative endometrium, whereas there was an increase in its expression in secretory endometrium from both patients and controls. CONCLUSION(S): Women with endometriosis show decreased number of apoptotic cells in eutopic endometrium. The abnormal survival of endometrial cells may result in their continuing growth into ectopic locations.

Apoptosis↗
PubMed2001

Effect of a combined oral contraceptive containing 3 mg of drospirenone and 30 microg of ethinyl estradiol on the human endometrium.

OBJECTIVE: To provide an in-depth assessment of the effects of the combined oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone (Yasmin, Schering AG, Berlin) on the endometrium by means of endometrial morphometry in comparison to an untreated cycle. DESIGN: The open, multicenter study consisted of one untreated precycle and 13 treatment cycles. SETTING: Four gynecologic clinics in Belgium, The Netherlands, and Switzerland were involved. PATIENT(S): Forty women with a history of regular menstrual cycles. INTERVENTION(S): Before the commencement of the trial, 3 months without any hormonal intake was obligatory. The first endometrial sample was done in the untreated precycle, adjusted to the day of LH peak plus 5 to 6 days. During the medication phase, endometrial samples were taken at cycle 3, 6 and 13. MAIN OUTCOME MEASURE(S): Primary outcome measure of the study was the morphologic assessment of the endometrium with measures such as glandular diameter, glandular epithelial height, and number of vacuolated cells per 1,000 glandular cells. Furthermore, the endometrial thickness was measured by ultrasound. RESULT(S): After 13 cycles of medication use the endometrium had an atrophic appearance in 63% of the subjects. The size of the glands, the glandular epithelial height, and the number of glands per square millimeter were already significantly reduced after 3 months' use. Histological and ultrasonographical evaluation of the endometrium indicated a suppression of the proliferative activity of the endometrium. CONCLUSION(S): The combination of 30 microg of ethinyl estradiol with 3 mg of drospirenone induces changes of the endometrium that are comparable with other combined oral contraceptives and exhibits a marked antiproliferative effect on the endometrium. The medication was proven to be an effective oral contraceptive and revealed good cycle control characteristics.

Adult↗
PubMed2002

Matrix metalloproteinase-2, membranous type 1 matrix metalloproteinase, and tissue inhibitor of metalloproteinase-2 expression in ectopic and eutopic endometrium.

OBJECTIVE: To investigate expression of matrix metalloproteinase-2 (MMP-2), membranous type 1 matrix metalloproteinase (MT1-MMP), and tissue inhibitor of metalloproteinase-2 (TIMP-2) in ectopic and eutopic endometrium from women with and without endometriosis throughout the menstrual cycle. DESIGN: Molecular studies in human tissue. SETTING: Reproductive immunology laboratory of a university medical center. PATIENT(S): Fifty-three premenopausal woman (23 with endometriosis and 30 without endometriosis) undergoing laparoscopic surgery. Endometrium and ectopic endometriosis tissue were obtained at the time of surgery. MAIN OUTCOME MEASURE(S): Messenger RNA and protein expression from eutopic and ectopic endometrium was analyzed by using quantitative competitive polymerase chain reaction, zymography, and Western blot assay. RESULT(S): Uterine endometrium from women with endometriosis expressed higher levels of MMP-2 and MT1-MMP and lower levels of TIMP-2 than did endometrium from normal women. CONCLUSION(S): Eutopic endometrium from patients with endometriosis may be more invasive and prone to peritoneal implantation because of greater expression of MMP-2 and MT1-MMP and lower expression of TIMP-2 messenger RNA, compared with endometrium from women without endometriosis. Thus, increased proteolytic activity may help to explain the invasive factors that result in endometriosis.

Adult↗