An ultrastructural study of implantation in the golden hamster. III. Initial formation and differentiation of decidual cells.
(9/1114)
The transformation of fibroblasts into decidual cells was studied ultrastructurally in golden hamsters pregnant for 3, 3 1/2, 4, 4 1/2, 5, or 5 1/2 days (post-ovulation). Cells within the endometrial stroma were generally separated from one another and spindle-shapted before blastocyst contact with the uterine epithelium. Once the epithelium enclosed the blastocyst (3 1/2 days), stromal cells adjacent to the blastocyst antimesometrially began to exhibit more extensive Golgi complexes with increased secretory activity. As differentiation proceeded the amount of cellular contact increased and various types of junctions formed between the cells. Throughout the period examined, intercellular space progressively decreased, while the cisternal width of the granular endoplasmic reticulum continually increased. Special organelles, whose functions remain unknown, first appeared in differentiating cells at 4 days (fibrils) and 5 1/2 days (crystalloid and 'dumb-bell' structures). (+info)
Zonula occludens-1 and E-cadherin are coordinately expressed in the mouse uterus with the initiation of implantation and decidualization.
(10/1114)
Two-way interactions between the blastocyst trophectoderm and the uterine luminal epithelium are essential for implantation. The key events of this process are cell-cell contact of trophectoderm cells with uterine luminal epithelial cells, controlled invasion of trophoblast cells through the luminal epithelium and the basement membrane, transformation of uterine stromal cells surrounding the blastocyst into decidual cells, and protection of the "semiallogenic" embryo from the mother's immunological responses. Because cell-cell contact between the trophectoderm epithelium and the luminal epithelium is essential for implantation, we investigated the expression of zonula occludens-1 (ZO-1) and E-cadherin, two molecules associated with epithelial cell junctions, in the mouse uterus during the periimplantation period. Preimplantation uterine epithelial cells express both ZO-1 and E-cadherin. With the initiation and progression of implantation, ZO-1 and E-cadherin are expressed in stromal cells of the primary decidual zone (PDZ). As trophoblast invasion progresses, these two molecules are expressed in stroma in advance of the invading trophoblast cells. These results suggest that expression of these adherence and tight junctions molecules in the PDZ serves to function as a permeability barrier to regulate access of immunologically competent maternal cells and/or molecules to the embryo and provide homotypic guidance of trophoblast cells in the endometrium. (+info)
Expression of cyclo-oxygenase types-1 and -2 in human fetal membranes throughout pregnancy.
(11/1114)
Human labour is associated with increased prostaglandin synthesis within the fetal membranes. We have studied the expression of the two isoforms of the central prostaglandin synthetic enzyme, cyclo-oxygenase (COX-1 and COX-2), in human fetal membranes throughout pregnancy, at mRNA, protein and activity levels. COX-1 mRNA expression was low in human amnion and chorion-decidua and did not change with gestational age. COX-2 mRNA expression in fetal membranes increased with gestational age, with significant up-regulation prior to the onset of labour and in association with labour. Protein concentrations of COX-1 did not change, whilst concentrations of COX-2 increased from the first to the third trimester. COX activity increased with gestational age and in association with labour, although prostaglandin production in fetal membranes collected after labour was reduced, suggesting reduced substrate supply. These data suggest that it is up-regulation of COX-2, rather than of COX-1, which mediates increased prostaglandin synthesis within the fetal membranes at term. Much of the increase in COX-2 expression precedes the onset of labour, suggesting that it is a cause, rather than a consequence, of labour. (+info)
Oxytocin receptor expression in human term and preterm gestational tissues prior to and following the onset of labour.
(12/1114)
Oxytocin receptor (OTR) mRNA expression has previously been demonstrated in human myometrium, decidua, chorion and amnion but the effect of gestational age and the onset of labour has not been determined in these individual tissues. Spatial OTR mRNA expression was examined by in situ hybridization and ligand binding was confirmed using autoradiography with the iodinated oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29]-vasotocin (125I-OTA). Tissue was collected at term (>37 weeks of gestation) or preterm (24-36 weeks of gestation) caesarean section and classified as labour (contractions every 5 min associated with cervical dilatation) or non-labour. OTR mRNA expression was measured as optical density units from autoradiographs. There was a highly significant (P<0.001) effect of tissue type on expression of OTR mRNA with expression greatest in myometrium, low in decidua and chorion and not detected in placenta. Similar results were obtained with the 125I-OTA-binding studies, indicating that the message was translated. Amnion had an apparently high level of both hybridization and 125I-OTA binding in some samples, but a lack of specificity prevented quantification of the signal in this tissue type. Term myometrium (labour and non-labour) had significantly higher (P<0.01) OTR mRNA expression than preterm myometrium, but there was no further increase in mRNA concentration associated with labour onset. In contrast, 125I-OTA binding in myometrium was already high at 33 weeks and did not increase further either later in pregnancy or with labour. In decidua there was no effect of gestational age or labour onset on OTR mRNA expression or 125I-OTA binding. In summary, OTR mRNA expression in the myometrium increased in late pregnancy whereas decidual expression was much lower and did not rise at term. (+info)
Endometrial steroid receptors during decidualization in rhesus monkey (Macaca mulatta); their modulation by anti-oestrogen CDRI-85/287.
(13/1114)
With a view to elucidating the hormonal control of decidualization in rhesus monkey, we studied the effects of CDRI-85/287, a potent anti-oestrogen, on endometrial steroid receptors in vivo and in vitro. Compound 85/287 was administered (i.m.) on days 8, 9 and 10 of steroid treatment cycle at a dose of 15 mg/monkey. Deciduoma was induced on day 16. Histological examination of endometrial tissue on days 24 and 30 of the cycle showed an apparent inhibition in uterine epithelial and subepithelial decidual cell plaque formation and a decrease in leukocytic infiltration into the stroma in anti-oestrogen-treated animals. As observed on day 24, a significant decrease in progesterone receptors (PR) (nuclear + cytosolic) was observed in the 85/287-treated group, whereas oestrogen receptor (ER) content remained unaltered. On day 30 total ER as well as total PR content was markedly reduced in treated animals. In-vitro results clearly demonstrated a competitive antagonism of 85/287 at the ER level only. The results are discussed in relation to the histological changes and modulation of steroid receptors, thereby suggesting the decidualization inhibitory activity of anti-oestrogen molecule 85/287 in primate species. (+info)
Leukocyte populations, hormone receptors and apoptosis in eutopic and ectopic first trimester human pregnancies.
(14/1114)
The implantation of trophoblast cells at extrauterine sites still results in decidualization. The objective of the present study was to compare decidualization at eutopic and ectopic implantation sites. Tissues from women undergoing elective termination of uterine pregnancy and from women with ectopic pregnancy were used to detect the presence of cells important for the maintenance of pregnancy, such as BCL-2+, CD56+, CD3+, CD8+ and CD68+ cells, and the presence of oestrogen (ER) and progesterone receptors (PR) by immunohistochemistry. In-situ detection of fragmented DNA was performed to identify apoptotic cells. The percentage of CD3+ cells among all immunocompetent cells in the tubal epithelium was 46.6% (39.9% of CD3+ were also CD8+); the other 53.4% were CD68+ cells. CD56+ cells were undetectable in ectopic decidua at the feto-maternal interface in ectopic tissue. In uterine decidua, we found 29.9% CD3+ cells (2.2% of CD3+ were CD8+), 51.6% CD56+ cells and 18.5% CD68+ cells. The ratio of BCL2+ to CD3+ cells in ectopic pregnancy was 0.41. In uterine pregnancy, the ratio of BCL-2 to CD3 was 0.44 and 0.39 for CD56. Tissues from both ectopic and uterine pregnancies were positive for PR. Fewer apoptotic cell bodies were present in ectopic pregnancy. The use of tissue obtained from ectopic pregnancy may become an excellent model to identify the mechanism of trophoblast invasion in eutopic pregnancies. (+info)
Co-stimulation of human decidual natural killer cells by interleukin-2 and stromal cells.
(15/1114)
At the late secretory phase of the menstrual cycle and in early pregnancy, the uterine mucosa is infiltrated by large numbers of natural killer (NK) cells with a distinctive phenotype (CD56bright CD16- CD3-) and large granular lymphocyte (LGL) morphology. Circulating CD56bright NK cells generally proliferate in the presence of interleukin-2 (IL-2), but it is clear that cofactors besides IL-2 are required for optimal response. In the bone marrow, this co-stimulating signal is provided by stromal cells. In the present study we observe that uterine CD56+ cells from early pregnancy decidua similarly proliferate vigorously when cultured with decidual stromal cells and a suboptimal dose of IL-2. This response is dependent on cell-cell contact, as no proliferation of decidual NK cells was observed when they were separated from stromal cells by a permeable cyclopore membrane. In addition, we have studied the expression of Bcl-2 by decidual CD56+ cells. Our results show that the microenvironment of the uterus is likely to have a significant influence on the proliferation and survival of uterine CD56+ cells. (+info)
Regulation of matrix metalloproteinase-9 in endometrium during the menstrual cycle and following administration of intrauterine levonorgestrel.
(16/1114)
Remodelling of endometrial tissues is fundamental to the cyclical changes that occur during the menstrual cycle, implantation and, in the absence of pregnancy, at menstruation. The enzyme matrix metalloproteinase-9 (MMP-9) is recognized as important in these processes but its regulation is not well defined. These studies have demonstrated that MMP-9 activity is present in the endometrium and exhibits cyclical changes in its distribution in the glandular and stromal cells. MMP-9 protein is present throughout the cycle with highest expression, as determined by semiquantitative analysis of specific MMP-9 immunoreactivity, in glandular cells during the mid secretory phase. A similar distribution was observed in first trimester decidua. In women with a levonorgestrel intrauterine system (LNG-IUS), which delivers high local concentrations of progestagen to the uterine cavity, MMP-9 is highly expressed in both endometrial glandular and stromal cells, and in the vasculature (in endothelial and perivascular cells). It can be concluded that MMP-9 is stimulated directly or indirectly by progesterone. Furthermore, MMP-9 may play a role in the remodelling of the endometrium that occurs during the menstrual cycle and in the aetiology of the morphological changes and breakthrough bleeding associated with long-term progestagen administration via a LNG-IUS. (+info)