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 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.

241. Changes in the expression of Annexin IV mRNA and protein in human endometrium

2005 ◽  
Vol 17 (9) ◽  
pp. 95
Author(s):  
A. P. Ponnampalam ◽  
P. A. W. Rogers
Keyword(s):  
Menstrual Cycle ◽  
Cellular Localization ◽  
Single Cells ◽  
Human Endometrium ◽  
Reproductive Age ◽  
Histological Evaluation ◽  
Secretory Phase ◽  
Proliferative Phase ◽  
Cyclic Changes ◽  
Late Secretory Phase

In a previous study investigating global gene expression throughout the menstrual cycle,1 Annexin 4 (ANXIV) was identified as having significant cyclic changes in human endometrium. ANXIV belongs to a ubiquitous family of Ca2+-dependent phospholipid and membrane-binding proteins. The aims of this study were to investigate the cellular localization and regulation of ANXIV mRNA and temporal expression of ANXIV protein in human endometrium during the menstrual cycle. mRNA Expression: The menstrual cycle was divided into seven stages by histological evaluation. Curettings of endometrium were collected from 60 cycling women. For cellular localization, tissues from eight endometrial curettings were dissociated with collagenase into single cells, separated into epithelial and stromal cell fractions and snap frozen. Total RNA was extracted and ANXIV mRNA was quantified by real-time PCR. Immunohistochemistry: Full thickness endometrial tissue was collected from 50 reproductive age women undergoing hysterectomy. Tissue sections were formalin-fixed and paraffin-embedded. Goat polyclonal ANXIV antibody was used to localize ANXIV protein. ANXIV mRNA was significantly upregulated in the whole tissue during mid-late secretory phase of the cycle, and was predominantly expressed in epithelial cells. ANXIV protein was detected in the luminal and glandular epithelium in high levels throughout the menstrual cycle except in early secretory (ES) phase. The intensity of immunostaining was stronger in the glands of the basalis compared to functionalis in early proliferative phase, however, by the late secretory phase the functionalis glands showed higher expression levels. ANXIV mRNA data are consistent with a role for progesterone in upregulating the expression of ANXIV, although protein levels remain high through menstruation and into the proliferative phase. ANXIV can indirectly inhibit prostaglandin production, which is important for implantation. Hence the low levels of ANXIV protein at ES phase may relate to processes involved in implantation. (1)Ponnampalam et al. (2004). Mol. Hum. Reprod. 10(12), 879–893.

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 Expression of Macrophage Inflammatory Protein-1β in Human Endometrium: Its Role in Endometrial Recruitment of Natural Killer Cells

2003 ◽  
Vol 88 (4) ◽  
pp. 1809-1814 ◽  
Author(s):  
Kotaro Kitaya ◽  
Takeshi Nakayama ◽  
Tomoharu Okubo ◽  
Haruo Kuroboshi ◽  
Shinji Fushiki ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Epithelial Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Secretory Phase ◽  
Proliferative Phase ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

Human endometrium is infiltrated by natural killer (NK) cells throughout the menstrual cycle. The number of endometrial NK cells is low in the proliferative phase, but acutely increases after ovulation, and reaches a peak in the late secretory phase, suggesting that endometrium recruits these leukocytes selectively from circulating peripheral blood. We investigated the expression of macrophage inflammatory protein (MIP)-1β, a potential chemoattractant for NK cells, in the endometrium. RT-PCR and ELISA revealed that MIP-1β is expressed in the endometrium throughout the menstrual cycle at both the message and protein levels. MIP-1β expression is stronger in the secretory phase endometrium than in the proliferative phase endometrium. Immunohistochemistry revealed that MIP-1β is localized in the surface epithelial cells, glandular epithelial cells, and perivascular stromal cells throughout the menstrual cycle. Stromal cells in a wider perivascular area became immunoreactive in the secretory phase. There was a strong correlation between the endometrial MIP-1β concentration and the number of endometrial NK cells. Progesterone significantly induced MIP-1β secretion from cultured endometrial stromal cells, whereas 17β-estradiol had a weak effect. These results suggest that endometrial MIP-1β may be involved in the recruitment of NK cells from circulating peripheral blood.

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.

scholarly journals Human Decidual Stromal Cells as a Component of the Implantation Niche and a Modulator of Maternal Immunity

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Kameliya Vinketova ◽  
Milena Mourdjeva ◽  
Tsvetelina Oreshkova
Keyword(s):  
Menstrual Cycle ◽  
Immune Tolerance ◽  
Immune Cells ◽  
Stromal Cells ◽  
Secretory Phase ◽  
Lymph Vessels ◽  
Uterine Mucosa ◽  
Specialized Tissue ◽  
The Relationship ◽  
Human Decidua

The human decidua is a specialized tissue characterized by embryo-receptive properties. It is formed during the secretory phase of menstrual cycle from uterine mucosa termed endometrium. The decidua is composed of glands, immune cells, blood and lymph vessels, and decidual stromal cells (DSCs). In the process of decidualization, which is controlled by oestrogen and progesterone, DSCs acquire specific functions related to recognition, selection, and acceptance of the allogeneic embryo, as well as to development of maternal immune tolerance. In this review we discuss the relationship between the decidualization of DSCs and pathological obstetrical and gynaecological conditions. Moreover, the critical influence of DSCs on local immune cells populations as well as their relationship to the onset and maintenance of immune tolerance is described.

scholarly journals Expression of Wilms’ Tumor Suppressor Gene (WT1) in Human Endometrium: Regulation through Decidual Differentiation

2001 ◽  
Vol 86 (12) ◽  
pp. 5964-5972
Author(s):  
Antonis Makrigiannakis ◽  
George Coukos ◽  
Anastasia Mantani ◽  
Prokopis Prokopakis ◽  
Geoffrey Trew ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Stromal Cells ◽  
Wilms Tumor ◽  
Suppressor Gene ◽  
Secretory Phase ◽  
Endometrial Stromal Cells ◽  
Protein Levels ◽  
Decidual Cells ◽  
Wt1 Protein

The Wilms’ tumor suppressor gene (WT1) encodes a zinc-finger containing transcription factor that is selectively expressed in the developing urogenital tract and functions as a tissue-specific developmental regulator. In addition to its gene-regulatory function through DNA binding properties, WT-1 also regulates transcription by formation of protein-protein complexes. These properties place WT-1 as a major regulator of cell growth and differentiation. In view of these observations, we studied WT1 mRNA and protein in human endometrial extracts and in endometrial stromal cells (ESCs) differentiating into decidual cells in vitro, by RT-PCR and Western blotting, respectively. WT1 protein expression was also studied in situ in the proliferative and the secretory phase of the menstrual cycle in the early pregnant state. Analysis by PCR of total RNA prepared from human ESCs demonstrated the presence of WT1 mRNA and four WT1 mRNA splice variants. Western blot analysis of nuclear protein extracts from ESCs yielded one immunoreactive protein of the expected size (approximately 52–54 kDa) recognized by the WT1 antibody. Immunohistochemical staining showed that WT1 protein is localized only to nuclei of human endometrial stromal cells. It remains constant in the proliferative and the secretory phase of the menstrual cycle and is increased remarkably during decidualization in early pregnancy. ESCs decidualized in vitro were investigated for WT-1 expression, which confirmed that decidualizing stimuli (E2, medroxy-progesterone-acetate, and relaxin for 12 d or cAMP and progesterone for 1–4 d) induced WT-1 mRNA (P &lt; 0.05) and increased protein levels (P &lt; 0.05). These data indicate that in humans the WT1 gene is expressed in ESCs and its mRNA and protein levels remain constant in the proliferative and the secretory phase of the menstrual cycle and that WT1 mRNA and protein expression increases significantly in ESCs when these cells differentiate into decidual cells.

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.

Intercellular contacts between stromal cells in the normal human endometrium throughout the menstrual cycle

1990 ◽  
Vol 21 (10) ◽  
pp. 1063-1066 ◽  
Author(s):  
T.H. Parmley ◽  
D.K. Roberts ◽  
N.J. Walker ◽  
D.V. Horbelt
Keyword(s):  
Menstrual Cycle ◽  
Stromal Cells ◽  
Human Endometrium ◽  
Intercellular Contacts ◽  
Normal Human
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