scholarly journals Global gene analysis of late secretory phase, eutopic endometrium does not provide the basis for a minimally invasive test of endometriosis

2008 ◽  
Vol 23 (5) ◽  
pp. 1063-1068 ◽  
Author(s):  
J.R.A. Sherwin ◽  
A.M. Sharkey ◽  
A. Mihalyi ◽  
P. Simsa ◽  
R.D. Catalano ◽  
...  
Reproduction ◽  
2009 ◽  
Vol 137 (4) ◽  
pp. 727-737 ◽  
Author(s):  
Carlos Ponce ◽  
Marisa Torres ◽  
Carolina Galleguillos ◽  
Hugo Sovino ◽  
M Angélica Boric ◽  
...  

In order to investigate the role of the nuclear factor κB (NFKB) pathway on gene expression in the eutopic endometrium in endometriosis, and in particular of interleukin-6 (IL6), we evaluated RELA, IκB kinase (CHUK), NFKBIA and IL6 expressions and NFKB DNA binding in eutopic endometrium from women with endometriosis. Eutopic endometrium was obtained from 37 women with endometriosis and 42 fertile women during laparoscopy. We analysed RELA, CHUK, NFKBIA and IL6 mRNA levels (RT-PCR); RELA, CHUK and NFKBIA proteins and p-NFKBIA/NFKBIA ratio (western blot); and NFKB binding (DNA shift assay) and IL6 concentration (ELISA) in endometrial explants. Our results indicate that mRNA and cytoplasmic proteins of RELA and CHUK exhibit constant levels in normal endometrium during the menstrual cycle. A dramatic increase (P<0.05) in NFKBIA mRNA expression, RELA nuclear presence and the mRNA and the protein of IL6 during late secretory phase was also observed in this tissue. By contrast, in eutopic endometrium from endometriosis patients, a decrease (P<0.05) in IL6 mRNA and protein (61%), NFKBIA mRNA (46%), p-NFKBIA/NFKBIA ratio (42%), RELA nuclear stromal (68%) and CHUK (48%) proteins were found exclusively during the late secretory phase compared with normal endometrium. In conclusion, the canonical activation of NFKB pathway is deregulated and may have reduced transcriptional function affecting NFKBIA and IL6 expression, genes related local proinflammatory processes. These molecular alterations observed during the late secretory phase in eutopic endometrium from endometriosis patients constitute a NFKB system dysfunction, suggesting that NFKB could be an important factor in endometriosis aetiology.


2000 ◽  
Vol 12 (2) ◽  
pp. 59 ◽  
Author(s):  
Noriyuki Takai ◽  
Tami Miyazaki ◽  
Isao Miyakawa ◽  
Ryoji Hamanaka

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.


2019 ◽  
Vol 105 (1) ◽  
pp. 219-230 ◽  
Author(s):  
Sergo Kasvandik ◽  
Merilin Saarma ◽  
Tanel Kaart ◽  
Ilmatar Rooda ◽  
Agne Velthut-Meikas ◽  
...  

Abstract Context Clinically used endometrial (EM) receptivity assays are based on transcriptomic patterning of biopsies at midsecretory endometrium (MSE) to identify the possible displacement or disruption of window of implantation (WOI) in patients with recurrent implantation failure (RIF). However, biopsies are invasive and cannot be performed in the same cycle with in vitro fertilization embryo transfer, while uterine fluid (UF) analysis is considered minimally invasive and can immediately precede embryo transfer. Objective To determine whether UF proteome can be used for WOI monitoring and whether it would highlight the etiology of RIF. Patients Paired early secretory endometrial (ESE) and MSE UF samples from six fertile control women for discovery, and an additional 11 paired ESE/MSE samples from controls and 29 MSE samples from RIF patients for validation. Results Using discovery mass spectrometry (MS) proteomics we detected 3158 proteins from secretory phase UF of which 367 undergo significant (q &lt; 0.05) proteomic changes while transitioning from ESE to MSE. Forty-five proteins were further validated with targeted MS, and 21 were found to display similar levels between control ESE and RIF MSE, indicating displacement of the WOI. A panel of PGR, NNMT, SLC26A2 and LCN2 demonstrated specificity and sensitivity of 91.7% for distinguishing MSE from ESE samples. The same panel distinguished control MSE samples from RIF MSE with a 91.7% specificity and 96.6% sensitivity. Conclusion UF proteins can be used for estimating uterine receptivity with minimal invasiveness. Women with RIF appear to have altered MSE UF profiles that may contribute to their low IVF success rate.


2009 ◽  
Vol 181 (3) ◽  
pp. 261-265 ◽  
Author(s):  
A.M. Gutiérrez ◽  
S. Martínez-Subiela ◽  
P.D. Eckersall ◽  
J.J. Cerón

1990 ◽  
Vol 258 (4) ◽  
pp. G542-G551 ◽  
Author(s):  
Naomi Uemura ◽  
Kenneth E. J. Dickinson ◽  
Yuji Horiguchi ◽  
Haruki Matsumoto ◽  
Basil I. Hirschowitz

Cells prepared from frog esophageal peptic glands by dispersal in low-Ca2+ medium (peptic acini) or 1 mM ethylene glycol-bis(-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)-containing medium ("EGTA cells") were compared. EGTA cells were characterized by decreased secretory responses to agonists [bombesin (BB), acetylcholine, and isoproterenol] and intracellular messenger activators (forskolin, 12-O-tetradecanoyl-phorbol-13-acetate), decreased relative intrinsic efficacies of muscarinic agonists, and somatostatin insensitivity. Decreased BB and muscarinic receptor responses were not associated with changes in receptor number or characteristics. The time course of BB- and acetylcholine-stimulated pepsinogen secretion indicated that the marked reduction was confined largely to the late secretory phase (2–30 min), dependent on extracellular Ca2+, rather than early phase (2 min) secretion, which is related to release of intracellular Ca2+. The defect could be reversed by the Ca2+ ionophore A23187. BB-stimulated intracellular Ca2+ mobilization measured with fura-2/AM was similar in the two cell preparations, whereas BB-stimulated 45Ca2+ uptake was reduced threefold in EGTA cells, and this defect was also reversed by A23187. Somatostatin inhibited both BB-stimulated secretion and 45Ca uptake by peptic acini, but it had no significant effect on these parameters in EGTA cells. Cytochalasin B inhibited BB stimulation in peptic acini but not EGTA cells. These findings suggest that peptic cells isolated with EGTA exhibit decreased secretory responses that are due at least in part to impairment of a mechanism for uptake of extracellular Ca2+.


2017 ◽  
Author(s):  
Keren Bahar-Shany ◽  
Georgina D. Barnabas ◽  
Limor Helpman ◽  
Ariella Yakobson-Siton ◽  
Tamar Perri ◽  
...  

2000 ◽  
Vol 124 (1) ◽  
pp. 131-136 ◽  
Author(s):  
H. WEHNER ◽  
R. MORRIS ◽  
M. LOGAN ◽  
D. HUNT ◽  
L. JIN ◽  
...  

Since the introduction of routine measles, mumps and rubella immunization for children in England and Wales in 1988, the incidence of mumps has declined steadily. We describe an outbreak of mumps in 1996 attacking 34 of a cohort of 98 schoolchildren born in 1982 and 1983. This is the largest outbreak in the UK since the introduction of the vaccine into the childhood immunization schedule. Salivary IgM assay was used as a simple, minimally invasive test to confirm the diagnosis. The occurrence of the outbreak demonstrates that British children who were just too old to receive mumps immunization in 1988 continue to be at risk of this disease as a result of diminished natural exposure. Further cases and outbreaks in this cohort are to be expected. Cohorts born before 1982 appear to be at less risk, presumably because of naturally acquired infection before the introduction of immunization.


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