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[Apoptosis and expression of relative genes in early pregnant chorionic villi and decidua].

OBJECTIVE: To investigate the effects of mifepristone on apoptosis and expression of relative genes in early pregnant chorionic villi and decidua. METHODS: The specimen of early pregnant chorionic villi and decidua obtained from 10 cases of requesting termination of pregnancy by curettage, 20 cases of mifepriston contragestation. The paraffin sections were used to determine apoptotic cells by TdT-mediated dUTP-biotin nick end labeling method, to identify bcl-2, bax, fas, fasL and proliferating cell nuclear antigen (PCNA) by immunohistochemistry, to demonstrate fas and fasL mRNA by in situ hybridization. RESULTS: In normal early pregnant specimens, apoptotic cells were mainly observed in syncytiotrophoblast, but not in cytotrophoblast cells, occasionally seen in decidua cells. The antigen of bax, fas, fasL were present in syncytiotrophoblast cells and decidua with lower amount. While bcl-2 antigen staining was strong in cytotrophoblastic cells and in decidua. PCNA protein was present in cytotrophoblastic and decidual cells only. In the specimens treated with mifepristone, apoptotic cells were increased in syncytiotrophoblastic cells of villi and visualized in decidua cells. The expression of fas, fasL and bax was also higher than that of normal. CONCLUSIONS: Mifepristone increased apoptosis in syncytiotrophoblastic and decidua cells, but had no effect on the expression of bcl-2 and PCNA.

Abortifacient Agents, Steroidal↗

[Changes of T-helper 1 and T-helper 2 ratio in peripheral blood and decidua in hypertensive disorder complicating pregnancy].

OBJECTIVE: To investigate the role of immune response induced by different T-helper 1 and T-helper 2 (Th1 and Th2) ratio in peripheral blood and decidua from patients with hypertensive disorder complicating pregnancy in the pathogenesis of the disease. METHODS: Peripheral blood and decidua from 12 non-pregnant women (no deciduas) (normal women group), 12 healthy pregnant women (healthy pregnant women group), 10 patients with gestational hypertension (gestational hypertension group), 25 patients with pre-eclampsia (PE) (including 10 patients with mild pre-eclampsia and 15 patients with severe pre-eclampsia) (pre-eclampsia group). Th1/Th2 ratio in peripheral blood and decidua was determined by flow-cytometrically. RESULTS: The ratio of Th1/Th2 in peripheral blood with normal women group is 10.5 +/- 1.5, the ratios of Th1/Th2 in peripheral blood and deciduas with healthy pregnant women group are 9.5 +/- 2.9 and 7.6 +/- 4.6 respectively, those with gestational hypertension group are 12.1 +/- 3.4 and 13.1 +/- 5.6 respectively, those with pre-eclampsia group are 16.8 +/- 3.8 and 26.7 +/- 9.4 respectively. The ratios of Th1/Th2 in peripheral blood and deciduas with pre-eclampsia group are much higher than those with other groups, when they are compared with each other, there are statistical difference (P < 0.05). And the ratio of Th1/Th2 with pre-eclampsia in deciduas is much higher than that in peripheral blood, comparing these two aspects, there is statistical difference (P < 0.001). The changes of Th1/Th2 ratio in gestational hypertension group is an intermediate between healthy pregnant group and pre-eclampsia group. CONCLUSIONS: Hypertensive disorder complicating pregnancy is a syndrome of Th1/Th2 cell balance disturbances in vivo. Over-expression of Th1 cells and imbalance of Th1/Th2 might lead to hypertensive disorder complicating pregnancy.

Adult↗

Suppression of lymphocyte alloreactivity by early gestational human decidua. I. Characterization of suppressor cells and suppressor molecules.

We examined the immunosuppressor role of the first trimester human decidua on lymphocyte alloreactivity in vitro in order to identify (1) the major cell classes in the decidua mediating the suppressor effect; (2) the stages in the lymphocyte alloreactive responses susceptible to the suppressor effects of the decidua; and (3) the precise nature of the suppressor molecules. Irradiated (2800 R), Ficoll-Paque-separated nucleated cells of the collagenase-dispersed early gestational (6.5-9.5 weeks menstrual age) decidua containing 70-94% typical decidual cells (identified on the basis of distinctive morphology and numerous cytoplasmic or surface markers) or their plastic-nonadherent fractions further enriched for decidual cells (approximately 96% pure) caused a strong dose-dependent suppression of the one way mixed lymphocyte reaction (MLR, i.e., proliferative response measured on Days 3, 4, or 5), when added at the onset of the mixed lymphocyte cultures (MLC). As few as 10(3) decidual cells caused a detectable inhibition of the MLR exhibited by 10(5)-1.5 X 10(5) responder lymphocytes. A smaller degree of suppression was noted with the plastic-adherent fractions of the early decidua (which retained all macrophages and granulocytes, but still included many decidual cells) or unfractionated cells of later gestational (10-13 weeks) decidua containing a higher incidence of leukocytes, granulocytes, and macrophages in particular, or the plastic-adherent fraction thereof, enriched for macrophages. Thus, decidual cells seem to represent an important suppressor cell class in the early gestational human decidua; however, suppression by decidual leukocytes, macrophages in particular, was also evident. The suppressor effect was unrelated to the major histocompatibility phenotype of the responder or the stimulator cells. It was not caused by cell crowding, since an equivalent number of irradiated K562 erythroleukemia cells had little effect on the MLR. The effect was exerted during both the initiation and the progression of the MLR. A delay in the addition of regulator cells progressively minimized the effect on the Day 4 MLR, but did not abolish it completely even when added as late as on Day 3. The major class of mediator molecules was identified as prostaglandins, primarily PGE2, on the basis of the following results: (1) the presence of indomethacin (10(-5) M) or varying dilutions of an anti-PGE2 antibody abrogated this suppression substantially or completely. (2) Addition of pure PGE2 (3 X 10(-7) to 1.1 X 10(-5) M), but not PGF2 alpha, reproduced a dose-dependent suppressor effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Count↗

The comparison of vessels in elective and spontaneous abortion decidua in first trimester pregnancies: importance of vascular changes in early pregnancy losses.

BACKGROUND: To determine whether adequate trophoblastic migration and maternal placental perfusion occurs in cases of early pregnancy loss, we compared vessels in elective abortion decidua with those in spontaneous abortion decidua. METHODS: Elective abortion decidua at 5-11 weeks (n = 40) were compared with spontaneous abortion decidua at 5-12 weeks (n = 25). Also normal late secretory endometrial biopsy specimens (n = 10) were examined. The cross-sections of veins and arteries were counted in 25 elective and 15 spontaneous abortion materials. The number of the veins that contain trophoblastic fragments and the number of the spiral arteries converted by trophoblasts were determined. Statistical significance by Mann-Whitney U and Spearman's correlation test was p < 0.05. RESULTS: All sets of decidua had dilated veins, but no secretory endometrium did. The ratio of converted spiral arteries to nonconverted arteries was much more in elective abortion decidua (113/938, 12.04%) than in spontaneous abortion decidua (11/511, 2.15%) (p < 0.001). CONCLUSIONS: The presence of converted arteries, dilated veins, and intravenous trophoblastic fragments in decidual specimens were evidence of intervillous circulation and placental perfusion by maternal circulation in the first trimester. Also the insufficient conversion of the arteries in spontaneous abortions might be responsible for many cases of early pregnancy loss.

Abortion, Induced↗

Immunological studies of mouse decidual cells. II. Studies of cells in artificially induced decidua.

Cells from artificially induced decidual tissue (deciduoma) in the mouse were examined for Thy-1 surface antigen and receptors for the Fc portion of immunoglobulin G (FcR) and compared with cells of the normal decidua from 6 to day 9 of pregnancy. It was shown that (1) Thy-1 antigen is present on the same proportion of cells in decidua and deciduoma on day 6 and day 7, (2) FcR-bearing cells can be detected in similar numbers on day 6 and day 7 but this does not increase on day 8 in deciduoma as it does in decidua, and (3) progesterone treatment after induction of decidualization allowed further increase of FcR-bearing cells in deciduoma. These results present further evidence of the similarity between deciduoma and decidua in the mouse. They indicate that these two membrane markers are present in the early decidua, regardless of the presence of an embryo, and suggest that progesterone may play a part in the increase of FcR-bearing cells in the decidua during pregnancy.

Animals↗

Metabolism of arachidonic acid and synthesis of prostanoids in human endometrium and decidua.

Arachidonic acid metabolism and prostanoid synthesis were investigated using [14C]-arachidonic acid (AA) in human endometrium obtained at different phases of the ovarian cycle and decidua in early pregnancy. Prostaglandins (PG) identified in endometrium and decidua were PGE2 and PGF2 alpha. The capacity for the production of PGE2 and PGF2 alpha was higher in the secretory phase of endometrium than in the proliferative phase, and the maximum formation of PGE2 and PGF2 alpha was found in the mid secretory phase and in the late secretory phase, respectively. However, the production of PGs was markedly suppressed in decidua. On the other hand, more than 70% of [14C]AA was incorporated into total neutral lipids, whereas less than 22% was incorporated into glycerophospholipids in both endometrium and decidua. Secretory endometrium showed a higher uptake of [14C]AA into glycerophospholipids than did proliferative endometrium, whereas the incorporation into neutral lipids was lower in secretory endometrium than in the proliferative phase. Moreover, decidua showed a similar pattern of incorporation of [14C]AA to the proliferative phase. The changes of arachidonic acid metabolism and PG formation in both endometrium and decidua are discussed in terms of implantation and maintenance of early pregnancy.

Arachidonic Acid↗

Differential distribution of CD4(+)CD25(bright) and CD8(+)CD28(-) T-cells in decidua and maternal blood during human pregnancy.

During pregnancy several maternal and fetal mechanisms are established to prevent a destructive immune response against the allogeneic fetus. Despite these mechanisms, fetus specific T-cells persist throughout gestation but little is known about the regulation of these T-cells. Recently, CD4(+)CD25(+) regulatory T-cells have been identified in human decidua. Human decidua forms the maternal part of the fetal-maternal interface and is subdivided in two distinct regions: the decidua (d.) basalis and the decidua (d.) parietalis. The aim of this study was to determine the distribution of specific T-cell subsets in d. basalis and d. parietalis in early and term pregnancy, with a special emphasis on the presence of CD4(+)CD25(bright) (regulatory) T-cells and CD8(+)CD28(-) (suppressor) T-cells. In addition, we compared phenotypic characteristics of decidua derived T-cell subsets with maternal peripheral blood (mPBL) T-cells and T-cells from non-pregnant controls. We identified significantly higher percentages of CD4(+)CD25(bright) and CD8(+)CD28(-) T-cells in decidua compared to peripheral blood suggesting an important role for these T-cell subsets locally at the fetal-maternal interface. The major differences in T-cell subset distribution and the presence of additional phenotypic differences between T-cells in d. basalis, d. parietalis and mPBL may reflect specific immunomodulatory functions of these T-cell subsets at these different sites during pregnancy.

CD28 Antigens↗

In vitro production of pregnancy-associated plasma protein A by human decidua and trophoblast.

Immunohistochemical techniques and direct measurements of pregnancy-associated plasma protein A (PAPP-A) have demonstrated the presence of PAPP-A in trophoblast and decidua. The purpose of the present study was to investigate the possibility that these tissues are capable of producing PAPP-A in vitro. Trophoblast and decidua were obtained from term deliveries and from legal surgical terminations of pregnancy (7 to 12 weeks). In addition to trophoblast and decidua, myometrium was also obtained during two hysterectomies in the first trimester of pregnancy. Tissues were incubated in medium 199 at 37 degrees C under an oxygen/carbon dioxide atmosphere. Media containing either pregnancy-associated serum or non-pregnancy-associated serum were changed after 8 hours of incubation in medium 199 alone. In addition to PAPP-A, human placental lactogen (hPL) and prolactin (Prl) were measured in homogenates and media by radioimmunoassays in order to confirm the viability of the cultured tissues. Addition of pregnancy-associated serum to the media induced a significant release of PAPP-A from trophoblast and decidua when compared to that in control cultures. Non-pregnancy-associated serum had no effect. Myometrium did not release any measurable PAPP-A into the medium even in the presence of pregnancy-associated serum. Cycloheximide added to pregnancy-associated serum significantly inhibited the release of PAPP-A from trophoblast and decidua. These last tissues, irrespective of the culture condition, released significantly more PAPP-A as well as hPL and Prl than was initially present in the tissue. These data demonstrate that PAPP-A is released in vitro by trophoblast and decidua (but not by myometrium) and that this release can be magnified by a factor present only in pregnancy-associated serum. The release of PAPP-A, hPL, and Prl is considered as a de novo production since concentration of these proteins are higher in media and tissues after incubation compared to concentrations initially present in the tissue before culture and since cycloheximide significantly inhibits the release of PAPP-A, Prl, and hPL from the cultured tissues.

Culture Media↗

Pregnancy-associated ectopic decidua (deciduosis) of the greater omentum. An analysis of 60 biopsies with cases of fibrosing deciduosis and leiomyomatosis peritonealis disseminata.

Ectopic decidua (deciduosis) of the omentum was investigated in biopsies taken during cesarean sections and in tubal pregnancies in 60 cases. An ectopic decidua of various abdominal organs was present in 48 further cases. All omentum biopsies showed decidual reactions:focal deciduosis in 97% and diffuse deciduosis in 3%. With increasing duration of pregnancy, there was vacuolar degeneration and fragmentation of the decidua cells as a manifestation of regressive changes. Co-expression of antibodies to vimentin, desmin and actin can be detected immunohistochemically. Ectopic decidua is a physiological phenomenon of pregnancy and arises from a progesterone-induced metaplasia of the pluripotential cells of the "subcelomic mesenchyma". The involution of the decidua takes place in the fourth to sixth week post partum. A fibrosing deciduosis of the omentum with development of a collagenous connective tissue at its surface is described as metaplasia of the hormone-dependent "subcelomic" mesenchyma. Immunohistochemically, a second case with leiomyomatosis peritonealis disseminata from the same investigation material shows the transformation of desmin- and actin-positive decidual cells into myofibroblasts and leiomyocytes in the form of a direct metaplasia. As pregnancy-associated mesenchymal metaplasias, ectopic decidua, fibrosing deciduosis and leiomyomatosis peritonealis disseminata depend on hormone and may regress post partum.

Adolescent↗

Immunoregulatory cells in human decidua: morphology, immunohistochemistry and function.

Suggestions that local intrauterine materno-fetal immune interactions may be important for normal pregnancy have led to investigation of immunoregulatory function by decidualised endometrium. Human decidua is complex and cell types may be difficult to distinguish at the light microscope level. Immunohistochemical techniques have allowed antigenic identification of cells within decidua and abundant leucocytes are present throughout pregnancy. Macrophages (CD14+) are abundant in decidua basalis and decidua parietalis throughout pregnancy and may be closely associated with extravillous trophoblast. Expression of class II MHC antigens and CD11c may suggest an immunological role but their content of lysosomal enzymes could indicate phagocytic functions. Antigen-presenting capacity has been noted in early human decidua and may be due to macrophages. Decidual macrophages have also been attributed with immunosuppressive function due to secretion of prostaglandin E2. Decidual granulated lymphocytes are abundant in the first trimester and correspond to the so-called endometrial stromal granulocytes. They express CD2, CD7, CD38 and NKH1 but are negative for classical T cell and NK cell markers and they do not express the IL2 receptor. Semipurified populations show low levels of cytotoxicity in a standard NK assay. Thus, immunohistochemical techniques have allowed characterisation of potentially immunocompetent cells in human decidua. However, their roles both in vitro and in vivo remain to be established with certainty.

Antigens, Surface↗

Localization of nuclear factor-kappa B (NF kappa B) and inhibitory factor-kappa B (I kappa B) in human fetal membranes and decidua at term and preterm delivery.

The human fetal membranes and decidua are thought to be involved in the onset of human parturition. These tissues produce and respond to various cytokines, which may be involved in preterm labour and possibly term labour. They also show increasing production of prostaglandins (PGs) with advancing gestation and labour. The expression of PGHS-2, a rate limiting enzyme in PG synthesis, is increased in the fetal membranes at labour. The gene for PGHS-2 and many of the cytokine genes (e.g. TNFalpha, IL-1, IL-6) are stimulated by the transcription factor NF kappa B. This factor is composed of two subunits, p50 and p65, which are localized in the cytoplasm bound to I kappa B. When activated I kappa B is metabolized, and p50, p65 translocate to the nucleus to activate various genes. The purpose of the present study was to examine the tissue and cellular distribution of p65 and I kappa B in the human fetal membranes and decidua throughout gestation. Term tissues were obtained prior to labour by elective caesarean section (n=10) or following vaginal delivery (n=10) and 10 preterm tissues were obtained following labour prior to 37 weeks gestation. None of the tissues had any evidence of infection. The immunoreactive NF kappa B and I kappa B were localized in the tissues. p65 protein was found in the nucleus and cytoplasm of cells in the amnion, chorion laeve and decidua. In the amnion and chorion laeve, no changes occurred in subcellular localization with advancing gestation or term labour. However, in the decidua, there was a marked increase in the nuclear localization of i.r. p 65 in tissues obtained at term when compared with tissues delivered preterm. In the case of I kappa B, it was localized to the cytoplasm of cells in all tissues and there was an increase i.r. I kappa B in decidua at term compared to preterm but no change occurred in the amnion or chorion. The increase in nuclear localization of p65 in the decidua that occurs with advancing gestation, highlights the potential importance of this factor in the regulation of parturition related genes in this tissue.

Cell Nucleus↗

Matrix metalloproteinase (MMP)-2 and MMP-9 and their inhibitor, TIMP-1, in human term decidua and fetal membranes: the effect of prostaglandin F(2alpha) and indomethacin.

Degradation and breakdown of gestational membranes and the adjacent decidua are essential processes for the advancement of labour. We have assessed the effect of prostaglandin (PG) synthesis on the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and tissue inhibitor of metalloproteinases (TIMP-1) in fetal membranes at the edge of the placenta and decidua, by using ex-vivo organ culture of the tissues in the absence or presence of PGF(2alpha) (0.1, 1.0 and 10 microg/ml) or a PG synthesis inhibitor, indomethacin (10(-4)-10(-6) mol/l). Conditioned media were assessed for MMP by zymography on gelatin containing sodium dodecyl sulphate-polyacrylamide gels and for TIMP-1 by Western blot analysis. Compared to the membranes, decidua produced significantly more MMP-2 and MMP-9 as well as TIMP-1. PGF(2alpha) caused a 2.4- and 1.9-fold increase in the production of MMP-2 and MMP-9 in the decidua, respectively (P < 0.05), and an 11.3-fold increase of the active form of MMP-2 (62 kDa) which could hardly be detected in basal culture conditions (P < 0.01). PGF(2alpha) decreased TIMP-1 production by 70% in the decidua. The production of MMP-2 and MMP-9 and TIMP-1 by the amniotic and chorionic membranes was not affected by PGF(2alpha). Indomethacin decreased the production of MMP-2 and MMP-9 by 78 and 35% in chorion, and by 70 and 58% in amnion, respectively (P < 0.05), but did not affect production in decidual tissue. Indomethacin increased the production of TIMP-1 in chorion and amnion [by 4.1- and 4.5-fold respectively (P < 0.01)], but had no effect on decidua. Cumulatively, PGF(2alpha) increases decidual gelatinolytic activity. Meanwhile the inhibition of PG production by indomethacin reduces total gelatinolytic activity in fetal membranes, possibly accounting for some of its labour-arresting property.

Cesarean Section↗

Sex steroid regulation of leukocyte traffic in human decidua.

Endometrial leukocyte subpopulations vary over the reproductive cycle, but no data exist on the mechanism regulating their recruitment into uterine tissue. This study has evaluated the role of progesterone in the recruitment of selected leukocyte populations in early pregnancy decidua. Decidua was collected from women in early pregnancy at the time of vacuum aspiration of the uterus 6, 12, 24 and 36 h after taking 200 mg mifepristone (RU486). Standard immunohistochemical techniques were employed to demonstrate the selected leukocyte populations in decidual tissue and these were analysed using imaged analysis. Fresh decidua was incubated in medium for 24 h and supernatants assayed for interleukin (IL-8) (neutrophil chemotactic factor) and MCP-1 (monocyte chemoattractant protein-1) content. Analysis of variance demonstrated a significant increase in tissue monocyte number in decidua 12-36 h after mifepristone administration. No significant changes in other leukocyte subpopulations were observed. Decidua IL-8 concentrations were significantly increased (P = 0.019) 6 h after mifepristone and decidual MCP-1 concentration rose (non-significant) and fell significantly (P = 0.029) between 6 and 12 h after mifepristone. Progesterone withdrawal may initiate a local cascade of events involving inflammatory mediators which in turn are responsible for the influx of monocytes. This influx may be essential in the process of shedding of endometrium or decidua since monocytes and neutrophils are important sources of proteases and collagenases. Furthermore, these cells are potential local sources of immunomodulatory cytokines.

Decidua↗

Zonal distribution of 11 beta-hydroxysteroid dehydrogenase types 1 and 2 messenger ribonucleic acid expression in the rat placenta and decidua during late pregnancy.

Glucocorticoid action in several target tissues is dependent on expression of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), and in the placenta 11 beta-HSD is thought to regulate transfer of active glucocorticoid to the fetus. This study compared expression of the two recognized 11 beta-HSD enzymes, types 1 and 2, in the rat placenta and decidua on Days 16 and 22 of gestation (term = Day 23). According to S1 nuclease protection analysis, although mRNA for 11 beta-HSD-1 was only just detectable in the labyrinth zone on Day 16, by Day 22 this expression had increased almost 20-fold. There was also an increase (approximately 2-fold) in 11 beta-HSD-1 mRNA in the basal zone between Days 16 and 22. In Day 16 decidua, 11 beta-HSD-1 mRNA was also highly expressed, but insufficient tissue was available for analysis on Day 22. Western blot analysis showed that immunoreactive 11 beta-HSD-1 (molecular mass 34 kDa) was present in those tissues with the highest 11 beta-HSD-1 mRNA expression (Day 16 decidua and Day 22 labyrinth zone). With respect to mRNA for 11 beta-HSD-2, high expression was observed in the decidua and labyrinth zone at Day 16, but in the latter this expression then declined 90% by Day 22. In contrast, expression of mRNA for 11 beta-HSD-2 increased more than 3-fold in the basal zone over the same period. Consistent with coexpression of the two 11 beta-HSD enzymes, both 11-oxoreductase and 11 beta-dehydrogenase bioactivity were clearly evident in all tissues, and each varied with stage of gestation. Specifically, 11 beta-dehydrogenase activity in the basal zone increased from 38 +/- 2% (mean +/- SEM) on Day 16 to 56 +/- 2% on Day 22, while 11-oxoreductase activity fell from 55 +/- 3% to 43 +/- 2% over the same period. In contrast, 11 beta-dehydrogenase activity in the labyrinth zone fell with advancing pregnancy (Day 16: 63 +/- 2%; Day 22: 48 +/- 2%). Both 11-oxoreductase (58 +/- 3%) and 11 beta-dehydrogenase (38 +/- 4%) activities were also evident in decidua at Day 16. In conclusion, this study shows that expression of 11 beta-HSD-1 and -2 is zone-specific in the placenta and maternal decidua. Moreover, opposite changes in the expression of the two enzymes occur in the basal and labyrinth zones of the placenta over the last days of pregnancy, indicative of distinct regulatory mechanisms and functional significance for the enzymes in the two placental zones.

11-beta-Hydroxysteroid Dehydrogenases↗

Pregnancy-associated ectopic decidua.

Extrauterine formation of decidua of stromal cells has been well described, particularly in the cervix and ovary. Sporadic reports have documented decidua formation of peritoneal surfaces and lymph nodes as well as ovarian ectopic decidua in pregnant patients. The apparent hormonal mechanism of this phenomenon suggests a relationship to endometriosis. Between 1983 and 1986, tissue from 10 pregnant patients (acquired from nine at cesarean section and from one at appendectomy) demonstrated submesothelial decidua formation in the form of microscopic nodules and diffuse cell arrangements in an edematous stroma. Some cases showed mild chronic inflammation. An intracytoplasmic lipofusin-type pigment was observed in one case. Four cases had diffuse omental involvement: two with small amounts of free peritoneal blood and two with peritoneal adhesions. Three cases were associated with paratubal cysts: two of these occurred in the uterine and appendiceal serosa, respectively, and one case showed involvement of a retroperitoneal lymph node associated with a pheochromocytoma. No specific gross observations were noted at surgery. There was no prior or subsequent evidence of endometriosis. A review of 958 elective tubal ligations performed between 1983 and 1985 demonstrated 52 examples (5.5%) of serosal decidua formation. Ectopic stromal decidua formation in pregnancy is: (a) a physiologic phenomenon related to the possible specialized sensitivity of the superficial coelomic stroma to progesterone; and (b) diffusely distributed in the peritoneum although it is a clinicopathologic process distinct from endometriosis.

Adult↗

Activation antigens during the proliferative and secretory phases of endometrium and early-pregnancy decidua.

BACKGROUND: Clarifying the normal distribution of activation antigens will contribute to database construction studies of monoclonal-antibody-based therapies in endometrial disorders. METHODS: In this study, endometrial tissue samples obtained during proliferative and secretory phases and decidual samples of early pregnancies were immunostained by the monoclonal antibodies anti-CD26, anti-CD30, anti-CD70, anti-CD71, and anti-CD98 using the indirect immunoperoxidase method. RESULTS: CD26 is expressed on the glandular epithelium in the endometrium and decidua. Endothelial CD26 is expressed less in the decidua when compared to the endometrium. CD30 is strongly expressed by decidual cells. It is only weakly expressed on endometrial and decidual vessels. Glandular and endothelial CD70 expression is mainly seen in the proliferative phase of the menstrual cycle. Glandular CD71 expression is less in the decidua when compared to the endometrium. Its expression on stromal cells is more in the secretory phase of the menstrual cycle and in early pregnancy deciduae. It is expressed on endometrial vessels but not on decidual vessels. Glandular CD98 is expressed more in the decidua when compared to the endometrium. This antigen exists on endometrial lymphocytes. It is strongly expressed on the endothelium in the endometrium and decidua. CONCLUSION: It seems that CD26 and CD70 are not involved in the functions of endometrial and decidual stromal cells. CD30 and CD71 are thought to be involved in decidualization. Absence of activation antigens other than CD98 on lymphocytes indicated an antigenic profile for large granular lymphocytes that is different from regular lymphocytes.

Adult↗

Predominance of Th2-promoting dendritic cells in early human pregnancy decidua.

Dendritic cells (DCs) are specialized antigen-presenting cells required for the priming and activation of T cells and promote the differentiation of naïve CD4+ T cells toward the T helper cell type 1 (Th1) or Th2 phenotype. Here, we describe the characterization of CD45+CD3-CD14-CD16-CD19-CD20-CD56-HLA-DRbright DCs from early human pregnancy decidua by flow cytometry. The percentage of DCs to mononuclear cells (leukocytes) in the decidua was significantly higher than that in the peripheral blood. Moreover, decidual DCs expressed costimulatory molecules such as CD80 and CD86 and a mature marker such as CD83 on their surface. The percentage of CD11c+CD123- myeloid DCs in the decidua was significantly higher than that in the peripheral blood. Conversely, the ratio of CD11c-CD123+ lymphoid DCs in the decidua was significantly lower than that in the peripheral blood. The number of interleukin (IL)-12-producing cells in the total DC population and the myeloid DCs in the decidua was significantly lower than that in the peripheral blood. IL-12 secretion by activated decidual myeloid DCs was significantly lower than that by peripheral DCs. Naïve CD4+ T cells primed with decidual myeloid DCs led to a higher percentage of Th2 cells in comparison with that with peripheral myeloid DCs. This finding was abolished by exogenous IL-12 administration with decidual myeloid DCs. Thus, the DCs in the decidua could regulate the Th1/Th2 balance to maintain a Th2-dominant state, leading to maintenance of pregnancy.

Adult↗

Inflammatory cytokine and thrombin regulation of interleukin-8 and intercellular adhesion molecule-1 expression in first trimester human decidua.

CONTEXT: Decidual neutrophil infiltration complicates spontaneous abortions associated with inflammation and hemorrhage. Transendothelial neutrophil migration into inflamed tissues involves IL-8-mediated chemoattraction, then neutrophil attachment to endothelial cell-expressed intercellular adhesion molecule-1 (ICAM-1). OBJECTIVE: The aim of this study was to assess IL-8 and ICAM-1 regulation in decidual inflammation and hemorrhage; the effects of the proinflammatory cytokines, TNFalpha, IL-1beta and the hemostatic, proinflammatory cytokine thrombin were measured on IL-8 expression in first trimester decidual cells (DCs), and ICAM-1 immunostaining was compared in normal, inflamed, and hemorrhagic first trimester decidua. DESIGN: Immunohistochemistry of human decidua and in vitro treatment of human decidual cells were performed. SETTING: The study was conducted at the Academic Medical Center. INTERVENTION: . DCs were passaged until they were leukocyte-free (CD45 free by FACS), then were incubated with estradiol or medroxyprogesterone acetate alone or with TNFalpha or IL-1beta or thrombin. Normal, inflamed, and hemorrhagic decidua were immunostained for ICAM-1 and the neutrophil marker CD14. MAIN OUTCOME MEASURE: ICAM-1 immunostaining was performed in decidua. IL-8 levels in DC-conditioned media were assessed by ELISA and immunoblotting; IL-8 mRNA levels were measured by quantitative RT-PCR. RESULTS: Endothelial cell ICAM-1 immunostaining was similar in normal and inflamed or hemorrhagic decidua. In cultured DCs, optimal concentrations of IL-1beta, TNFalpha, and thrombin elevated secreted IL-8 levels by 1083 +/- 261-, 370 +/- 77-, and 45 +/- 15-fold, respectively (mean +/- SEM; P < 0.05; n = 8). The effects were dose dependent and were unaffected by medroxyprogesterone acetate. Western blotting confirmed the ELISA results, and corresponding effects on IL-8 mRNA levels were observed. CONCLUSIONS: Cytokine/thrombin-enhanced DC IL-8 expression interacts with constitutively expressed ICAM-1 in decidual endothelium to modulate neutrophil trafficking into hemorrhagic and inflamed first trimester decidua.

Cells, Cultured↗