scholarly journals Epigenetic profile of endometrial proliferation in the different morphotypes of endometrial hyperplasia

2021 ◽  
pp. 68-78
Author(s):  
O.L. Gromova ◽  
V.O. Potapov ◽  
D.A. Khaskhachykh ◽  
O.P. Finkova ◽  
O.V. Gaponova ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Stromal Cells ◽  
Endometrial Hyperplasia ◽  
Nuclear Antigen ◽  
Secretory Phase ◽  
Normal Endometrium ◽  
Proliferative Phase ◽  
Epigenetic Profile ◽  
Glandular Cells ◽  
Er Expression

Research aim: to investigate the proliferative status of endometrium in the different morphotypes of endometrial hyperplasia based upon the identification of key molecular markers of the cell cycle.Materials and methods. Endometrial samples taken from 137 women were investigated: 40 – normal endometrium (NE), 61 – non-atypical endometrial hyperplasia (ЕH), 36 – atypical hyperplasia (AHE). Expression of gene cyclin D1, nuclear antigen Кі-67, glycoproteins Е-cadherin and β-catenin, estradiol receptors (ER) and progesterone receptors (PGR) were investigated. Results. ER expression of NE was high in the proliferative phase and decreased significantly in the secretory phase. PGR expression was high in both phases. ER expression of EH in glandular (180 ± 8.3) and in stromal cells (170.5 ± 4.1) exceed the indicators of the secretory phase. PGR expression in the stromal cells of EH (197.5 ± 9.3) exceed significantly indicators of NE. ER and PGR expression significantly and reliably decreased if there was AHE. ER expression of glandular cells was 2.6 times lower (74.6 ± 3.9) compere to proliferative NE (p <0.05) and 2.4 times lower to EH (р <0.05). ER of stromal AHE cells dropped to 30.3 ± 2.8, which was 5.5–5.6 times lower than in the proliferative NE and EH (p <0.002). PGR expression was 2.5–2.7 times lower (71.1 ± 2.3) in AHE glands than in NE and 2.8 times lower than in EH (p <0.05). Gene cyclin D1 expression was reliably increased in AHE cells compere to NE and EH. Protein Кі-67 expression in the glandular cells of EH was 2.6 times lower (p <0.05) and in AHE 2.9 times lower (p <0.05) than NE proliferative phase. We discovered strong direction to decreasing Е-cadherin expression in EH and it was lowest for AHE. Opposite direction was expression of β-catenin. The highest numbers of positive samples were observed in AHE and it was 100%. The highest numbers of negative β-catenin samples were in the NE cells (32,5–35%).Conclusion. The epigenetic profile investigation of endometrial hyperplasia will be useful for future development of carcinogenesis risk stratification, identifying patients with high risk of endometrial cancer and also for choosing the optimal way to influence the pathological process in the endometrium.

Polo-like kinase expression in normal human endometrium during the menstrual cycle

2000 ◽  
Vol 12 (2) ◽  
pp. 59 ◽  
Author(s):  
Noriyuki Takai ◽  
Tami Miyazaki ◽  
Isao Miyakawa ◽  
Ryoji Hamanaka
Keyword(s):  
Menstrual Cycle ◽  
Stromal Cells ◽  
Cellular Proliferation ◽  
Secretory Phase ◽  
Ki 67 ◽  
Normal Endometrium ◽  
Proliferative Phase ◽  
Normal Human ◽  
Late Secretory Phase

The enzyme, polo-like kinase (PLK), is a mammalian serine/threonine kinase involved in cell cycle regulation. A great deal of evidence regarding the role of PLK in the cell cycle has been obtained through studies of cultured cells, though little is known about its function or even expression in vivo. The endometrium undergoes rapid proliferation and differentiation under ovarian steroid hormone control during the 28-day cycle. Thus, normal endometrium provides an excellent model in which to study the hormone dependency of PLK expression. In the present study, we examined the features of PLK expression in 20 samples of normal human endometrium during the menstrual cycle. The expression of Ki-67 and proliferating cell nuclear antigen (PCNA) were also examined as markers of proliferation. Immunohistochemical studies showed that PLK staining was detected in the basement membrane of many endometrial glands, stromal cells, and some endothelial cells. The number of PLK-positive endometrial gland cells was significantly higher in the late proliferative phase (19.16% 4.98%) and the early secretory phase (19.28% 4.99%) than in the early proliferative phase (2.60% 2.33%) or the late secretory phase (5.76% 2.16%) (P<0.0001). PLK expression seemed to be correlated with the expression of Ki-67 and PCNA in many endometrial glands and stromal cells particularly in the late proliferative phase, reflecting a role of PLK in cellular proliferation. Nevertheless, in the early secretory phase, at which point the expression of Ki-67 and PCNA decreased in endometrial glands, PLK was strongly expressed. This finding suggests that PLK may have some post-mitotic functions in certain specialized cell types. Although the highest expression of PLK was observed in the late proliferative and the early secretory phases, the expression drastically decreased in the late secretory phase. These findings, taken together, indicate that the expression of PLK in normal endometrium fluctuates over the course of the menstrual cycle, suggesting in turn that PLK is associated with hormone-dependent cellular proliferation and that hormone functions may be involved in its regulation.

scholarly journals RECEPTORS OF ENDOMETRIUM IN PREMENOPAUSAL WOMEN WITH DIFFERENT MORPHOTYPES OF ENDOMETRIAL HYPERPLASIA

2021 ◽  
Vol 11 (1(39)) ◽  
pp. 33-38
Author(s):  
Oleksandra Gromova ◽  
V. Potapov ◽  
D. Khaskhachykh ◽  
O. Gaponova ◽  
G. Kukina
Keyword(s):  
Positive Reaction ◽  
Stromal Cells ◽  
Endometrial Hyperplasia ◽  
Early Stage ◽  
Polyclonal Antibodies ◽  
Statistical Processing ◽  
Premenopausal Women ◽  
H Index ◽  
Glandular Cells ◽  
Er Expression

Introduction. Endometrial hyperplasia is a commonproblem among premenopausal women. There are nonatypical (EH) and atypical (AH) morphotypes according tocytological atypia. Despite a mostly favorable prognosisof EH, risk of progression to atypia is nearly 2% per year.The next problem is absence of clear criteria on which casewill have an unfavorable prognosis and EH will progress toAH and endometrial cancer. Markers of response of EH andAH to the first line therapy such as progestin are not wellinvestigated either. Investigation of ER and PGR expressionin normal (NE) and hyperplastic endometrium can be usefulfor future development of treatment algorithms in differentendometrial hyperplasia morphotypes and forecastingresponses to progestin therapy.Objective: To investigate the expression of estradiol andprogesterone receptors in the glandular and stromal cells ofnormal endometrium and in the different morphotypes ofendometrial hyperplasia.Material and Methods: Endometrial samples taken from137 women were investigated: 40 – with normal proliferativeand secretory endometrium (NE), 61 – endometrialhyperplasia without atypia (ЕH), 36 – endometrialhyperplasia with atypia (AH). Routine histopathologicaland immunohistochemical (IHC) examination of nuclearantigens in the endometrium samples was conducted. Then,IHC examination was carried out on the paraffin blocksusing monoclonal and polyclonal antibodies and systems ofvisualization. Expression of estradiol (ER) and progesterone(PGR) receptors was investigated. Taking into account thatcells with positive reaction to ER and PGR have significantdifferences in the intensity of IHC coloring, we used theaverage value or H-index according to the number of cellswith positive reaction and reaction intensity. Values from0 to 50 on the H-index were considered for the absence ofER and PGR expression, from 50 to 100 - expression ofantigens to receptors was considered as weakly positive;100 points or more - as positive. Statistical processing ofresults was done using licensed program Statistics (V 6.1;Statsoft, USA).Results: ER expression of EH both in glandular cells (180±8.3) and stromal cells (170.5±4.1) was close to resultsof proliferative NE (193.1±12.2 in the glandular and 166±9.7in the stromal cells), but 1,43 times exceeded indicators inthe glandular (180±8.3 vs 125.4±5.7; p<0.05) and 1.9 timesin the stromal cells (170.±4. vs 122.±4.; p<0.5) of secretoryNE. PGR expression in the glandular cells of EH wasalmost the same as this indicator of NE. PGR expressionin the stromal cells of EH was 197.±9.3 points and it wassignificantly higher compared to NE. On the contrary, withAHE ER and PGR expression significantly and reliablydecreased. ER expression of glandular cells (74.6±3.9points) was 2.6 times lower compared to proliferative NE(p<0.05) and 2.4 times lower to EH (р<0.05). ER of stromalAHE cells dropped to 30.3±2.8, which was 5.5 times lowerthan in NE of the proliferative phase (p<0.002) and 5.6times lower than in EH (p<0.002). PGR expression had thesame direction and also decreased. AHE glandular PGRexpression (71.1±2.3) was 2.7-2.5 times lower than thisindicator in the proliferative and secretory NE respectively(p<0.05). Reliable differences in PGR expression betweenAHE and EH were found. Glandular PGR expression indexAHE was 2.8 times lower than the same EH indicator(p<0.05), stromal one was 2.4 times lower (p<0.05).Conclusion: Estradiol and progesterone receptors dataof endometrium will be useful for future developmentof carcinogenesis risk stratification at the early stage,identifying patients with high risk of endometrial cancerand also for choosing the optimal way to influence thepathological process in the endometrium.

scholarly journals Endometritis in the bitch: Immunohistochemical localization of cyclooxygenase 2

2020 ◽  
Vol 10 (2) ◽  
pp. 157-163
Author(s):  
María Carla García Mitacek ◽  
Romina Gisele Praderio ◽  
María Cecilia Stornelli ◽  
Rodolfo Luzbel De la Sota ◽  
María Alejandra Stornelli
Keyword(s):  
Stromal Cells ◽  
Endometrial Hyperplasia ◽  
Inflammatory Cells ◽  
Immunohistochemical Localization ◽  
Cyclooxygenase 2 ◽  
Immunohistochemical Expression ◽  
Normal Endometrium ◽  
Pathophysiological Mechanisms ◽  
Mixed Breed ◽  
Strong Staining

Background: In several mammals, subfertility or infertility associated with endometritis was reported. Although there have been studies about endometritis in bitches, the pathophysiological mechanisms are not completely known.Aim: This study aimed to evaluate the immunohistochemical expression of Cyclooxygenase 2 (COX2) in clinically healthy bitches with normal uterine tissue and bitches with endometritis.Methods: Forty-eight mixed breed bitches in diestrus were used. Uterine biopsies were collected for diagnosis [normal endometrium (n = 15; NE), cystic endometrial hyperplasia (n = 1), atrophy (n= 2), acute endometritis (n = 9; AE), subacute endometritis (n = 7; SE), and chronic endometritis (n = 14; CE)]. Immunostaining and quantification of positively stained cells was performed on full-thickness uterine biopsies. Data were analyzed by the GLIMMIX procedure of SAS.Results: COX2 immunostaining was scattered and restricted to cells in the stroma in bitches with NE. However, in bitches with endometritis, strong staining was observed in the luminal epithelium, glandular epithelium, and stromal cells. Staining was also observed in inflammatory cells localized in the stroma as well as inside of the glands. The percentage of COX2 positive stromal cells in bitches with AE, SE, and CE was significantly higher compared with NE (p < 0.005). In addition, the percentage of COX2 positive stromal cells in bitches with SE, and CE was significantly lower compared with AE (p < 0.003).Conclusion: COX2 could be involved in the pathophysiological mechanisms producing endometritis without the presence of cystic endometrial hyperplasia in bitches. However, further researches on this topic are required. Keywords: Bitch, COX2, Endometritis, Immunohistochemical.

Matrix metalloproteinases and their tissue inhibitors in endometrial remodelling and menstruation

1996 ◽  
Vol 5 (3) ◽  
pp. 185-203 ◽  
Author(s):  
Lois A Salamonsen ◽  
David E Woolley
Keyword(s):  
Stromal Cells ◽  
Adult Life ◽  
Secretory Activity ◽  
Luminal Surface ◽  
Secretory Phase ◽  
Stromal Fibroblasts ◽  
Proliferative Phase ◽  
Decidual Cells ◽  
Normal Menstrual Cycle ◽  
Tissue Oedema

The architecture of the human endometrium is extensively remodelled during the course of each normal menstrual cycle, unlike most other tissues and organs which undergo very little change during adult life. During menstruation, when loss of most of the functionalis layer occurs, there is concomitant epithelial regrowth; repair of the luminal surface is complete almost as bleeding ceases. During the proliferative phase of the cycle and under the influence of rising oestrogen levels, the stromal cells, glands and blood vessels undergo rapid proliferation which results in tissue thickening. Following ovulation (around day 14 of the idealized 28-day cycle), the secretory phase of the cycle is characterized by increasing tortuosity of the spiral arterioles and glands and increased glandular secretory activity. After about day 22, decidualization of many of the stromal fibroblasts also occurs, the resultant decidual cells having many characteristics typical of epithelial cells. Periods of tissue oedema are apparent both in mid-proliferative (days 8–11) and mid-secretory (days 20–23) endometrium. Late in the cycle, there is regression of the tissue as menstruation is initiated.

scholarly journals The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization

2020 ◽  
Author(s):  
Sangappa B. Chadchan ◽  
Vineet K. Maurya ◽  
Pooja Popli ◽  
Ramakrishna Kommagani
Keyword(s):  
Menstrual Cycle ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Converting Enzyme ◽  
Endometrial Stromal Cell ◽  
Secretory Phase ◽  
Endometrial Stromal Cells ◽  
Angiotensin Converting Enzyme 2 ◽  
Proliferative Phase ◽  
Human Endometrial Stromal Cell

AbstractSTUDY QUESTIONIs SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE 2) expressed in the human endometrium during the menstrual cycle, and does it participate in endometrial decidualization?SUMMARY ANSWERACE2 protein is highly expressed in human endometrial stromal cells during the secretory phase and is essential for human endometrial stromal cell decidualization.WHAT IS KNOWN ALREADYACE2 is expressed in numerous human tissues including the lungs, heart, intestine, kidneys and placenta. ACE2 is also the receptor by which SARS-CoV-2 enters human cells.STUDY DESIGN, SIZE, DURATIONProliferative (n = 9) and secretory (n = 6) phase endometrium biopsies from healthy reproductive-age women and primary human endometrial stromal cells from proliferative phase endometrium were used in the study.PARTICIPANTS/MATERIALS, SETTING, METHODSACE2 expression and localization were examined by qRT-PCR, Western blot, and immunofluorescence in both human endometrial samples and mouse uterine tissue. The effect of ACE2 knockdown on morphological and molecular changes of human endometrial stromal cell decidualization were assessed. Ovariectomized mice were treated with estrogen or progesterone to determine the effects of these hormones on ACE2 expression.MAIN RESULTS AND THE ROLE OF CHANCEIn human tissue, ACE2 protein is expressed in both endometrial epithelial and stromal cells in the proliferative phase of the menstrual cycle, and expression increases in stromal cells in the secretory phase. The ACE2 mRNA (P < 0.0001) and protein abundance increased during primary human endometrial stromal cell (HESC) decidualization. HESCs transfected with ACE2-targeting siRNA were less able to decidualize than controls, as evidenced by a lack of morphology change and lower expression of the decidualization markers PRL and IGFBP1 (P < 0.05). In mice during pregnancy, ACE2 protein was expressed in uterine epithelial and stromal cells increased through day six of pregnancy. Finally, progesterone induced expression of Ace2 mRNA in mouse uteri more than vehicle or estrogen (P < 0.05).LARGE SCALE DATAN/A.LIMITATIONS, REASONS FOR CAUTIONExperiments assessing the function of ACE2 in human endometrial stromal cell decidualization were in vitro. Whether SARS-CoV-2 can enter human endometrial stromal cells and affect decidualization have not been assessed.WIDER IMPLICATIONS OF THE FINDINGSExpression of ACE2 in the endometrium allow SARS-CoV-2 to enter endometrial epithelial and stromal cells, which could impair in vivo decidualization, embryo implantation, and placentation. If so, women with COVID-19 may be at increased risk of early pregnancy loss.STUDY FUNDINGS/COMPETING INTEREST(S)This study was supported by National Institutes of Health / National Institute of Child Health and Human Development grants R01HD065435 and R00HD080742 to RK and Washington University School of Medicine start-up funds to RK. The authors declare that they have no conflicts of interest.

RAD001 (Everolimus) Can Prevent Tamoxifen-Related Endometrial and Stromal Hyperplasia

2009 ◽  
Vol 19 (3) ◽  
pp. 375-379 ◽  
Author(s):  
Evrim Erdemoglu ◽  
Mehmet Güney ◽  
Gülnur Take ◽  
Seren Gülşen Giray ◽  
Tamer Mungan
Keyword(s):  
Proliferating Cell Nuclear Antigen ◽  
Endometrial Hyperplasia ◽  
Nuclear Antigen ◽  
Group 4 ◽  
Glandular Cells ◽  
Group 3 ◽  
Group 5 ◽  
Group 2 ◽  
Proliferating Cell ◽  
Kinase Pathway

The mechanism of tamoxifen-associated endometrial hyperplasia and cancer is not elicited. RAD001 inhibits a target protein in phosphatidyl kinase pathway, which is involved in endometrial hyperplasia and cancer. We investigated whether endometrial hyperplasia can be prevented through inhibition of the target of rapamycin by RAD001. Sixty BALB/c mice underwent oophorectomy and were divided into 6 groups: group 1, placebo group; group 2, tamoxifen-treated (4 mg/kg per 24 hours); group 3, estradiol-treated (4 mg/kg per 24 hours); group 4, RAD001-treated (1.5 mg/kg per 24 hours); group 5, tamoxifen (4 mg/kg per 24 hours)-and-RAD001 (1.5 mg/kg per 24 hours)-treated; and group 6, estradiol (4 mg/kg per 24 hours)-and-RAD001 (1.5 mg/kg per 24 hours)-treated. The count of glands, the length of epithelium, and immunohistochemical staining of proliferating cell nuclear antigen were analyzed. The count of total glands and the epithelial length were 30.8 (7.1) and 126 (43.4) μm, 53 (8.1) and 162.5 (34.8) μm, 65.2 (13.6) and 401.4 (44.0) μm, and 82.0 (5.2) and 444.7 (57.8) μm in the placebo-, the RAD001-, the tamoxifen-, and the estradiol-treated groups, respectively (P < 0.05). Although addition of RAD001 to estradiol did not decrease the count of total glands and the epithelial length, addition of RAD001 to tamoxifen did (43.3 [13.3] and 218.0 [29.2] μm, P < 0.05). The immunoreactive score of proliferating cell nuclear antigen is significantly decreased by the addition of RAD001 to either tamoxifen or estradiol in the epithelial and glandular cells. RAD001 can prevent tamoxifen-associated and estrogen-related endometrial hyperplasias in mice. RAD001 also decreases stromal cell proliferation in the tamoxifen-treated mice.

scholarly journals FKBP4 is regulated by HOXA10 during decidualization and in endometriosis

Reproduction ◽  
2012 ◽  
Vol 143 (4) ◽  
pp. 531-538 ◽  
Author(s):  
Huan Yang ◽  
Yuping Zhou ◽  
Benjiamin Edelshain ◽  
Frederick Schatz ◽  
Charles J Lockwood ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Stromal Cells ◽  
Secretory Phase ◽  
Endometrial Stromal Cells ◽  
Eutopic Endometrium ◽  
Protein Levels ◽  
Proliferative Phase ◽  
Progestin Receptor ◽  
Fertile Women

FKBP4 (FKBP52) and FKBP5 (FKBP51) are progestin receptor (PR) co-chaperone proteins that enhance and inhibit, respectively, progestin-mediated transcription by PR. Here, we examinedFKBP4andFKBP5expression in the eutopic endometrium of fertile women with endometriosis and effects of FKBP4 and FKBP5 on the decidualization of human endometrial stromal cells (HESCs), and assessed HOXA10 regulation of FKBP4. Expression ofFKBP4mRNA was increased in the late proliferative phase and remained elevated throughout the secretory phase.FKBP5expression was low and remained constant throughout the menstrual cycle. Compared with controls,FKBP4mRNA expression was decreased in the endometrium of women with endometriosis, whereas no significant endometriosis-related change was seen forFKBP5. Cultured HESCs were treated with eitherFKBP4orFKBP5siRNA and then decidualized by incubation with progesterone (P4) and 8-bromoadenosine cAMP. Treatment of HESCs withFKBP4siRNA resulted in 60% lowerIGFBP1expression. In contrast, incubation withFKBP5siRNA did not significantly decreaseIGFBP1expression duringin vitrodecidualization.HOXA10andFKBP4expression increased in parallel duringin vitrodecidualization. In HESCs, overexpressed HOXA10 enhanced FKBP4 mRNA and protein levels, whereas HOXA10 knockdown decreased FKBP4 mRNA and protein levels compared with controls. Similarly, duringin vitrodecidualization,FKBP4expression was decreased in HOXA10-silenced cells. EnhancedHOXA10expression in HESCs elicits a decidualization mediating increase inFKBP4expression. The findings are consistent with the observation that women with endometriosis have diminishedFKBP4expression leading to impaired decidualization and infertility. The P4resistance seen in endometriosis may be mediated through HOXA10-regulatedFKBP4expression.

scholarly journals Histopathological Study of Endometrium in Infertility: Experience in A Tertiary Level Hospital

2018 ◽  
Vol 8 (2) ◽  
pp. 132-137
Author(s):  
Mousumi Ahmed ◽  
Nazma Afroze ◽  
Mahjabin Sabiha
Keyword(s):  
Endometrial Hyperplasia ◽  
Tertiary Care ◽  
Histopathological Study ◽  
Care Hospital ◽  
Secretory Phase ◽  
Secondary Infertility ◽  
Morphological Pattern ◽  
Infertile Women ◽  
Proliferative Phase ◽  
Primary Infertility

Background: Infertility refers to inability to achieve conception even after one year of unprotected coitus by a couple. It is a global health problem and affects 8-10% couple worldwide. Infertility can be primary or secondary and there are many causes of infertility involving both male and female partner. A wide range of investigations can be done to find out the causes of infertility. Endometrial biopsy or curettage or aspiration followed by histopathological study is a safe procedure. It not only shows the hormonal response of endometrium but also diagnose other endometrial pathology causing infertility. The study was performed to find out the morphological pattern of endometrium in infertile women in a tertiary care hospital to find out the causes of infertility and subsequent treatment of the patients.Methods: It was a cross sectional prospective study, conducted in the Department of Histopathology and Cytopathology in a tertiary care hospital in Dhaka for a period of two years from Jan 2015 to Dec 2016. It included 196 referred cases endometrial curettage or biopsy samples of infertile women, collected between days 21 to 23 of menstrual cycle. The endometrial samples obtained from patients suffering from diseases other than infertility were excluded from the study. Hematoxylin and Eosin (H&E) stained histopathological slides were prepared from the samples and examined under microscope. Reported results and relevant data were recorded in SPSS data collection sheet and statistical analysis was carried out.Results: A total of 196 cases of endometrial biopsy or curettage samples of both primary and secondary infertile women were studied. Age ranged from 20 years to 40 years with a mean age of 29.91±4.32years. 70.92% cases presented with primary infertility and 29.08% cases presented with secondary infertility. Proliferative phase/anovulation (41.33%) was found as the most common morphological pattern of endometrium in infertile women followed by secretory phase (40.30%). Endometrial hyperplasia, inadequate sample, nonspecific ednometritis and tuberculous endometritis were found in 10.72% , 6.12% , 6.12% and 0.51% cases respectively. In primary infertility, proliferative phase / anovulation (43.17%) was also the predominant pattern followed by secretory phase (37.40%) and endometrial hyperplasia (11.52%). Whereas, secretory phase( 47.37%) was the most common pattern of endometrium in secondary infertility, followed by proliferative phase (36.37%) and endometrial hyperplasia (8.77%). Primary infertility was most frequently presented in 26-30 years of age, whereas, secondary infertility was more prevalent in later age group.Conclusion: Histopathological study of endometrium gives us valuable information of endometrium in infertility. Morphological pattern of endometrium in our study was quite similar to other studies conducted in different countries with some variations. This study may help other studies in future to find out the cause of infertilityBirdem Med J 2018; 8(2): 132-137

Receptorial and mitochondrial apoptotic pathways in normal and neoplastic human endometrium

2005 ◽  
Vol 15 (3) ◽  
pp. 523-528 ◽  
Author(s):  
M. Di Paola ◽  
G. Loverro ◽  
A. M. Caringella ◽  
G. Cormio ◽  
L. Selvaggi
Keyword(s):  
Cytochrome C ◽  
Endometrial Carcinoma ◽  
Caspase 3 ◽  
Reproductive Organs ◽  
Human Endometrium ◽  
Caspase 8 ◽  
Secretory Phase ◽  
Normal Endometrium ◽  
Proliferative Phase ◽  
Apoptotic Pathways

Under normal conditions, in human endometrium, apoptotic and antiapoptotic factors play an important role in tissue homeostasis. Abnormalities of apoptosis, a process implicated in several events in the reproductive organs, may contribute to neoplastic transformation. The present study aimed to investigate the involvement of both the receptorial and the mitochondrial pathways of apoptosis in normal endometrium and in endometrial carcinoma, by measuring caspase-3 and caspase-8 activities and cytosolic cytochrome c levels. Twelve endometrial carcinomas and nine normal endometrial specimens (four in mild proliferative phase, five in late secretory phase) were included in this study. Cytosolic fractions, obtained by differential centrifugation of tissue homogenates, were analyzed for caspase-3 and caspase-8 activities, as well as for cytochrome c content. Caspase-8 activity in normal secretory phase endometrium was higher than that in the proliferative phase and in the endometrial carcinoma. Moreover, higher cytochrome c levels were detected in endometrial carcinoma with respect to normal secretive endometrium. No significant differences were found in caspase-3 activity between normal and pathologic endometrium. The results obtained suggest that in normal endometrium, apoptosis takes place through the activation of both receptorial and mitochondrial pathways. Defects in both these pathways may contribute to the development of endometrial carcinoma.

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