First Trimester Histiotrophe Shows Altered Sialylation Compared with Secretory Phase Glycoconjugates in Human Endometrium

Placenta ◽  
2010 ◽  
Vol 31 (7) ◽  
pp. 576-580 ◽  
Author(s):  
C.J.P. Jones ◽  
J.D. Aplin ◽  
G.J. Burton
2019 ◽  
Author(s):  
Douglas A Gibson ◽  
Arantza Esnal-Zufiaurre ◽  
Cristina Bajo-Santos ◽  
Frances Collins ◽  
Hilary OD Critchley ◽  
...  

AbstractStudy questionDoes the oestrogen receptor isoform, ER46, contribute to regulation of endometrial function?Summary answerER46 is expressed in endometrial tissues during the proliferative and secretory phases and is the predominant ERα isoform in first trimester decidua. ER46 is abundantly expressed in uterine NK (uNK) cells and localised to the cell membrane. Activation of ER46 regulates the function of human uNK cells by increasing cell motility.What is known alreadyOestrogens acting via their cognate receptors are essential regulators of endometrial function and play key roles in establishment of pregnancy. ER46 is a 46kDa truncated isoform of full length ERα (ER66, encoded by ESR1) that contains both ligand and DNA binding domains. Expression of ER46 in human endometrium has not been investigated previously. ER46 is located at the cell membrane of peripheral blood leukocytes and mediates rapid responses to oestrogens. UNK cells are a phenotypically distinct (CD56brightCD16-) population of tissue-resident immune cells that regulate vascular remodelling within the endometrium and decidua. We have shown that oestrogens stimulate rapid increases in uNK cell motility. Previous characterisation of uNK cells suggests they are ER66-negative but expression of ER46 has not been characterised. We hypothesise that uNK cells express ER46 and that rapid responses to oestrogens are mediated via this receptor.Study design, size, durationThis laboratory-based study used primary human endometrial (n=24) and decidual tissue biopsies (n=30) as well as uNK cells which were freshly isolated from first trimester human decidua (n=18).Participants/materials, setting, methodsPrimary human endometrial and first trimester decidual tissue biopsies were collected using methods approved by the local institutional ethics committee (LREC/05/51104/12 and LREC/10/51402/59). The expression of oestrogen receptors (ER66, ER46 and ERβ) was assessed by qPCR, western blot and immunohistochemistry. Uterine Natural Killer (uNK) cells were isolated from first trimester human decidua by magnetic bead sorting. Cell motility of uNK cells was measured by live cell imaging: cells were treated with oestradiol (E2)-BSA (10nM equivalent), the ERβ-selective agonist 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN; 10nM) or vehicle control (DMSO).Main results and the role of chanceER46 was detected in proliferative and secretory phase tissues and was the predominant ERα isoform in first trimester decidua samples. Immunohistochemistry revealed ER46 was co-localised with ER66 in cell nuclei during the proliferative phase but detected in both the cytoplasm and cell membrane of stromal cells in the secretory phase and in decidua. Triple immunofluorescence staining of decidua tissues identified expression of ER46 in the cell membrane of CD56-positive uNK cells which were otherwise ER66-negative. Profiling of isolated uNK cells confirmed expression ER46 and localised ER46 protein to the cell membrane. Functional analysis of isolated uNK cells using live cell imaging demonstrated that activation of ER46 with E2-BSA significantly increased uNK cell motility.Limitations, reasons for cautionExpression patterns in endometrial tissue was only determined using samples from proliferative and secretory phases. Assessment of first trimester decidua samples was from a range of gestational ages which may have precluded insights into gestation specific changes in these tissues. Our results are based on in vitro responses of primary human cells and we cannot be certain that similar mechanisms occur in situ.Wider implications of the findingsE2 is an essential regulator of reproductive competence. This study provides the first evidence for expression of ER46 in human endometrium and decidua of early pregnancy. We describe a mechanism for regulating the function of human uNK cells via expression of ER46 and demonstrate that selective targeting with E2-BSA regulates uNK cell motility. These novel findings identify a role for ER46 in human endometrium and provide unique insight into the importance of membrane-initiated signalling in modulating the impact of E2 on uNK cell function in women.Study funding/competing interest(s)These studies were supported by MRC Programme Grants G1100356/1 and MR/N024524/1 to PTKS. HODC was supported by MRC grant G1002033.


2005 ◽  
Vol 1041 (1) ◽  
pp. 136-143 ◽  
Author(s):  
COURTNEY P. BOND ◽  
LAURA J. PARRY ◽  
CHRISHAN S. SAMUEL ◽  
HELEN M. GEHRING ◽  
FIONA L. LEDERMAN ◽  
...  

2001 ◽  
Vol 86 (4) ◽  
pp. 1823-1834 ◽  
Author(s):  
Xiao Feng Li ◽  
D. Stephen Charnock-Jones ◽  
Eko Zhang ◽  
Susan Hiby ◽  
Shazia Malik ◽  
...  

Angiogenesis is essential for endometrial growth and repair, and disruption of this process may lead to common disorders of women, including menorrhagia and endometriosis. In pregnancy, failure of the endometrial spiral arterioles to undergo remodeling leads to preeclampsia. Here we report that in addition to vascular endothelial growth factor A (VEGF-A), human endometrium expresses messenger ribonucleic acids (mRNAs) encoding VEGF-C, placenta growth factor (PlGF), the angiopoietins, angiopoietin 1 (Ang1) and Ang2, and the receptors VEGFR-3 (Flt-4), Tie 1, and Tie 2. Levels of VEGF-C, PlGF, and Tie 2 changed during the menstrual cycle. Intense hybridization for VEGF-C and PlGF mRNAs was found in uterine nature killer cells in secretory phase endometrium and for Ang2 mRNA in the same cells in the late secretory phase. Interleukin-2 (IL-2) and IL-15 up-regulated VEGF-C, but not PlGF or Ang2, mRNA levels in isolated NK cells. Conditioned medium from decidual NK cells did not induce human umbilical vein endothelial cell apoptosis. These results indicate that human endometrium expresses a wide range of angiogenic growth factors and that uterine nature killer cells may play an important role in the abnormal endometrial angiogenesis that underlies a range of disorders affecting women.


2009 ◽  
Vol 4 (1) ◽  
pp. 48-59 ◽  
Author(s):  
Priyanka Rai ◽  
Venkatesh Kota ◽  
Curam Sreenivasacharlu Sundaram ◽  
Mamta Deendayal ◽  
Sisinthy Shivaji

1969 ◽  
Vol 61 (3) ◽  
pp. 425-431 ◽  
Author(s):  
Gunnar Rydén ◽  
Ingvar Sjöholm

ABSTRACT Using tritium-labelled oxytocin with a high specific activity, the halflife in the blood and the urinary excretion of intravenously injected oxytocin were followed in the female. The following groups of patients were studied: normally menstruating women during different phases of the menstrual cycle, women using a combination of gestagenic and oestrogenic hormones for oral contraception, and pregnant women in the first and second trimester. The pregnant women were admitted to the hospital for legal abortion in the 10th–20th week of gestation. In the proliferative phase, t½ was 272 seconds (n = 14), in the secretory phase 221 seconds (n = 5), and in women using oral contraceptives 199 seconds (n = 10). In pregnant women during the first trimester, t½ was 178 seconds (n = 6). The corresponding value in women examined during the 14th–17th weeks and during the 18th–20th weeks of gestation was 295 seconds (n = 6) and 282 seconds (n = 6), respectively. T½ was also determined within 24 h of abortion in patients in the second trimester, where the abortion was induced by intra-amniotic instillation of 50% glucose. In all cases a decrease in t½ was found. The decrease was most marked in women during the 18th–20th weeks of gestation. Altogether 25–50% of the radioactivity injected was recovered in the urine from pregnant women within 3 h of the injection. Thin-layer chromatography of the urine did not reveal the presence of any intact oxytocin. The results demonstrate that the disappearance of oxytocin from the blood seems to be influenced by the sex hormones. Thus, an oestrogendominated stage shows a lower disappearance rate, whereas gestagens produce the reverse effect. The pronounced decrease in t½ in pregnant women immediately after abortion might be due to a change to a more progesterone-dominated stage induced by the death of the foetus, or by an alteration in the affinity of oxytocin to the myometrium.


2009 ◽  
Vol 57 (9) ◽  
pp. 871-881 ◽  
Author(s):  
Udo Jeschke ◽  
Hermann Walzel ◽  
Ioannis Mylonas ◽  
Panos Papadopoulos ◽  
Naim Shabani ◽  
...  

Mucin 1 (MUC1) is a glycoprotein in human endometrium and is abundant at the luminal epithelial surface in the receptive phase. It has a highly glycosylated ecto-domain that contains keratan sulfate chains, that disappears at the time of implantation. In addition, the glycoforms on MUC1 differ in fertile and infertile women. Therefore the aims of this study were investigations on glycosylation of MUC1 with the Thomsen-Friedenreich (TF) epitope on normal human endometrium throughout the menstrual cycle and binding of galectin-1 on the TF epitope in the endometrium and the expression of galectin-1 on the human oocyte. Human endometrial tissue was obtained from 54 premenopausal patients and was immunohistochemically analyzed with monoclonal antibodies against MUC1, TF epitope, galectin-1, and biotinylated galectin-1. In addition, human oocytes were analyzed for TF, galectin-1 expression, and galectin-1 binding. We identified a significant upregulation of MUC1 and TF epitope and, in addition, galectin-1 binding in glandular epithelium and epithelial apical surface tissue from proliferative to secretory phase. With double staining experiments, we identified a coexpression of TF and MUC1 in the early secretory phase and galectin-1 binding to TF during the same period of time. In addition we identified TF epitope and galectin-1 expression plus binding on the human oocyte and irregularly fertilized oocytes. Upregulation of TF epitope on the glandular epithelium and epithelial apical surface tissue in the secretory phase and binding of galectin-1 at the same time show the possibility of galectin-1–mediated trophectoderm binding to the endometrium within the window of implantation.


2004 ◽  
Vol 89 (7) ◽  
pp. 3477-3485 ◽  
Author(s):  
Courtney P. Bond ◽  
Laura J. Parry ◽  
Chrishan S. Samuel ◽  
Helen M. Gehring ◽  
Fiona L. Lederman ◽  
...  

1975 ◽  
Vol 80 (4) ◽  
pp. 719-731 ◽  
Author(s):  
A. R. Krishnan ◽  
B. K. Bajaj ◽  
V. Hingorani ◽  
K. R. Laumas

ABSTRACT A study of the metabolism of oestradiol in the human endometrium and myometrium of the proliferative and secretory phases of the cycle showed that the conversion of oestradiol to oestrone by endometrium in the proliferative phase was higher than that in the secretory phase. The decreased metabolic activity of the secretory phase endometrium was attributed to the influence of progesterone on the endometrium. The metabolic conversion of oestradiol to oestrone was enhanced when pyridine nucleotides were added to the system. The conversion of oestradiol to oestrone was maximum in the cytoplasmic and nuclear fractions of the endometrium. Furthermore, the conversion of oestradiol was low in all the subcellular fractions of the myometrium as compared with the endometrial subcellular fractions. The presence of co-factors increased the metabolic conversion of oestradiol to oestrone in the subcellular fractions of the endometrium. The presence of 17β-hydroxysteroid oxidoreductase was indicated in all the subcellular fractions. A correlation was found between the amount of oestradiol and oestrone bound to the receptors in the uterus and the rate of metabolism of oestradiol in the uterus. The physiological significance of metabolism of oestradiol and the hormone action are discussed.


2011 ◽  
Vol 23 (1) ◽  
pp. 201
Author(s):  
H. Yang ◽  
E.-B. Jeung

Plasma membrane Ca2+-pumping ATPases (PMCA) play a critical role in maintaining cellular Ca2+ homeostasis. The PMCA mRNA are encoded on 4 genes, designated PMCA1 to PMCA4. In a previous study, we found that both PMCA1 and PMCA4 are expressed at similar levels in astrocytes and in neurons. Although PMCA1b is expressed in the uterus of rats during the oestrous cycle, the expression of PMCA1 and its potential roles has not been elucidated during the menstrual cycle in the human endometrium. Thus, in the current study, the expression pattern of PMCA1 was examined to predict its roles in the human endometrium during the menstrual cycle. Human uterine tissues (total n = 40) were separated into 3 groups according to menstrual cycle phase: menstrual phase, proliferative phase (early, mid, late), and secretory phase (early, mid, late). Using real-time PCR and Western blot analysis, uterine expression of PMCA1 mRNA and protein increased to 1.5-fold in the early-, mid- and late-proliferative phases in the endometrium of the human uterus, compared with other menstrual phases. In addition, uterine PMCA1 was abundantly localised in the cytoplasm of the luminal and glandular epithelial cells in the menstrual phases, indicating that this protein may participate in the uterine Ca balance of the human endometrium during the menstrual cycle. Taken together, these results suggest that a high level of uterine PMCA1 expression may be involved in reproductive functions during the menstrual cycle of humans.


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