Function Of Decidual Cells Research Articles

Isolation of Primary Human Decidual Cells from the Fetal Membranes of Term Placentae.

The maternal decidua is a transient and dynamic tissue that functions as an immunoprivileged matrix related to nutritional and endocrine processes. The function of decidual cells is key to the success of embryo implantation and the maintenance of pregnancy with a positive maternal-fetal outcome. Therefore, establishing a method to optimize the isolation of primary decidual cells is essential. Our protocol described here provides a good yield of decidual cells in an optimized time.

Transcriptomic profiling of canine decidualization and effects of antigestagens on decidualized dog uterine stromal cells

Maternal-stroma derived decidual cells, the only cell population in the canine placenta expressing the nuclear progesterone (P4) receptor (PGR), are crucial for the maintenance of canine pregnancy. Decreased circulating progesterone (P4) levels, or blockage of PGR function with antigestagens, terminate canine pregnancy. As an in vitro model for canine decidualization, dog uterine stromal (DUS) cells can be decidualized in vitro with cAMP. The antigestagens aglepristone and mifepristone ablate the expression of decidualization markers in DUS cells (e.g., PGR, PRLR, IGF1 or PTGES). Here, the transcriptome profile of DUS cells was investigated to acquire deeper insights into decidualization-associated changes. Additionally, effects mediated by antigestagens (competitive PGR blockers) in decidualized cells were assessed. Decidualization led to the upregulation of 1841 differentially expressed genes (DEGs, P and FDR < 0.01) involved in cellular proliferation and adhesion, mesenchymal-epithelial transition, extracellular matrix organization, and vaso- and immunomodulation. The 1475 DEGs downregulated after decidualization were mostly associated with apoptosis and cell migration. In decidualized DUS cells, aglepristone modulated 1400 DEGs and mifepristone 1558 DEGs. Interestingly, around half of the identified DEGs were modulated by only one of the antigestagens. In all cases, however, PGR-blockage was mainly associated with an inversion of several decidualization-induced effects. Comparison between antigestagen-mediated effects and transcriptional changes in the canine placenta at term allowed the identification of 191 DEGs associated with diminished cell proliferation and adhesion, and vascular and immune modulation. This study emphasizes the importance of P4/PGR signaling for decidual cell function, providing new insights into the maintenance of canine pregnancy.

Transposable Elements Continuously Remodel the Regulatory Landscape, Transcriptome, and Function of Decidual Stromal Cells.

Gene expression evolution underlies the origin, divergence, and conservation of biological characters including cell-types, tissues, and organ systems. Previously we showed that large-scale gene expression changes in decidual stromal cells (DSCs) contributed to the origins of pregnancy in eutherians and the divergence of pregnancy traits in primates and that transposable elements likely contributed to these gene expression changes. Here we show that two large waves of TEs remodeled the transcriptome and regulatory landscape of DSCs, including a major wave in primates. Genes nearby TE-derived regulatory elements are among the most progesterone responsive in the genome and play essential roles in orchestrating progesterone responsiveness and the core function of decidual cells by donating progesterone receptor binding sites to the genome. We tested the regulatory abilities of 89 TE consensus sequences and found that nearly all of them acted as repressors in mammalian cells, but treatment with a histone deacetylase inhibitor unmasked latent enhancer functions. These data indicate that TEs have played an important role in the development, evolution, and function of primate DSCs and suggest a two-step model in which latent enhancer functions of TEs are unmasked after they lose primary repressor functions.

Carbon disulfide induced decidualization disorder in the mice uterus at the window of implantation.

Carbon disulfide (CS2) is regarded as a common occupational poison that is widely used in the textile industry in China. Our previous research suggests that CS2 can induce significant implantation disorders in pregnant mice; however, the specific mechanism remains unclear. Uterine conception in mice must undergo decidualization, which is the prerequisite for propitious blastocyst implantation into the endometrium. Therefore, in this study, we established models of pregnant mice to explore the toxic effects of CS2 on decidualization to elucidate the basic mechanism of implantation disorder after CS2 exposure. The uterine tissues were immediately collected according to the predetermined endpoints to measure the expression levels of IGFBP1 and PRL (markers of decidualization differentiation), IL-11 (representing the secretory function of decidual cells), AKT and pAKT by western blotting, RT-PCR, immunohistochemical staining, H&E staining and ELISA. N-carbamoyl glutamic acid (NCG) acted as an agonist of AKT to verify the upstream regulatory mechanism of decidualization disorder by CS2. The results showed that the normal reaction of decidual transformation was obviously disrupted by CS2 upon 3.5 dpc and 4.5 dpc exposure. The blastocyst did not adhere to the epithelium after 3.5 dpc-exposure and did not invade the endometrium after 4.5 dpc-exposure, resulting in its suspension in the uterine cavity, stagnation and eventual loss. The proteins expression levels were decreased by 95.2% for IGFBP1 and 76.2% for PRL at the 4.5 dpc endpoint after 3.5 dpc CS2 exposure compared with the control. Simultaneously, the mRNA and protein expression levels of IL-11 in uterine tissues were significantly reduced by CS2, and consistent decreasing trends over time were observed for IGFBP1 and PRL, compared with the control. Additionally, the ratio of pAKT/AKT protein expression was decreased by 72.2% and 94.8% at 12h and 18h after 3.5 dpc exposure and by 53.3% and 74.3% at 6h and 12h after 4.5 dpc exposure, respectively, compared with the corresponding controls. Furthermore, NCG could recover the IGFBP1 and PRL protein expression, which was increased by 27.5% and 52.3% at 4.5 dpc and 6.5 dpc, respectively, after 3.5 dpc exposure for IGFBP1 and by 30.3% at 6.5 dpc after 4.5 dpc exposure for PRL, compared with CS2 exposure alone. Collectively, this study suggested that the decidualization disorder caused by CS2 at the window of implantation in pregnant mice, which is triggered by pAKT, contributed to the implantation disorder and eventually led to embryo loss. It is worth noting that our study may provide a new perspective and reference for exploring the toxic mechanism of implantation disorder and even infertility in harmful circumstances.

MiR-21a inhibits decidual cell apoptosis by targeting Pdcd4

Decidualization of endometrial stromal cells (ESCs) accompanied with embryo implantation is a key process in mammalian reproduction. Evidence suggests that maintenance of decidual cells function is essential. As a critical part in post-transcriptional gene regulation, microRNAs (miRNAs/miR) have been confirmed to be involved in decidualization. However, whether microRNAs regulate decidual cells function has not been reported. Aiming to clarify the role and potential mechanism of miRNAs in decidual cells, artificial induced decidualization model in mice was established. There are 94 differentially expressed miRNAs (≥two-fold change) between decidualized and non-decidualized tissues, including 60 upregulated and 34 downregulated miRNAs. Of the differentially expressed miRNAs, mmu-miR-21a is up-regulated. RT-qPCR also confirmed the up-regulation of mmu-miR-21a following decidualization in vivo and in vitro, and bioinformatic analysis and luciferase activity assay revealed Pdcd4 to be the target gene of mmu-miR-21a. Inhibition of mmu-miR-21a restrained secretory function of decidual cells induced by mESCs, accompanied with increase of Pdcd4 expression and resulted in the increase of cell apoptosis. In addition, we also determined the expression of hsa-miR-21 and Pdcd4 in human proliferative endometrial tissues and decidua tissues. hsa-miR-21 showed higher expression in human decidua tissues compared with proliferative endometrial tissues, while expression of Pdcd4 was contrary to that of hsa-miR-21. Similarly, cell apoptosis increased significantly in human endometrial stromal cell line in response to inhibition of hsa-miR-21. Collectively, we conclude that mmu-miR-21a/hsa-miR-21 may play a key role in regulating the function of decidual cells by inhibiting cell apoptosis through targeting Pdcd4.

Stimulation of rats fetuses growth by transplantation of rats bone marrow cells or human umbilical cord blood cells during gastrulation

Background & Aim In humans and animals with interstitial transplantation and hemochorial type of the placenta decidual cells (DC) differentiates in the uterus, and form the maternal part of the placenta. In the absence of DC development stops at the stage of merosome. Previously, we have shown that non-pregnant rats bone marrow cells transplantation (BMT) stimulates the development of DC in pseudo-pregnant rats. It is of interest to study the effect of pregnant rats bone-marrow cells on fetal development during transplantation in the early stages of pregnancy, as well as whether human umbilical cord blood cells have a similar effect. Methods, Results & Conclusion Bone marrow mononuclear cells (BMMC) of 4-13 days of pregnancy rats were administered intravenously to does of the same gestation period. The weight and morphology of the fetuses were evaluated on the 18th day of pregnancy. It was found that BMMC transplantation on 7-9 days of pregnancy significantly increased the weight of fetuses to 835 ± 15 mg compared to the weight of non-pregnant does (745 ± 11 mg) and the weight of does fetuses, which were administered BMMC of diestrus does (772 ± 9 m). Administration of BMMC on 11-12 days of pregnancy reduced fetal weight to 587 ± 5 mg. Also the umbilical cord blood mononuclear cells (UCBMC) was used in the study, which were administered subcutaneously in doses of 26 or 71 × 106 cells per 250 g of animal weight. Fetal weight on the 18th day of pregnancy was the maximum (856 ± 8 mg) with the administration of UCBMC on the 9th day of pregnancy. With the administration of UCBMC on day 11 of pregnancy fetal weight was reduced to 803 ± 19 mg. The dose reduction of the UCBMC to 26 × 106 resulted in the weight of the fetus on the 9th day of pregnancy decrease to 813 ± 17 mg. Thus, both rats BMMC and a human UCBMC stimulate 18th day of pregnancy fetus weight after administration to the female rats on the 7th, 8th and 9th days of pregnancy in the period of gastrulation. No morphological abnormalities were found in the fetuses. There is also no increase in post-implantation death, which indicates that the increase in fetal weight is not the result of compensatory growth. Similar results of transplantation of different types of cells indicate a general mechanism of fetal growth stimulation. It is possible that the result develops due to stimulation of decidual cell function but particular mechanisms of it are still need future researches.

Innate immune function of the human decidual cell at the maternal–fetal interface

The aim of the study was to investigate the innate immune function of decidual cells from term unlabored pregnancies by determining Toll-like receptor presence and function. Using immunohistochemistry, reverse transcriptase polymerase chain reaction and NF-κB-luciferase plasmid transfection, Toll-like receptor presence and function was determined. Decidual cells express Toll-like receptors 1, 2, 4 and 6 which respond to lipopolysaccharide and peptidoglycan stimulation producing Interleukin-8. Decidual cells from women at term have innate immune function and are capable of producing Interleukin responses to bacterial ligands.

Preimplantation factor (PIF) upregulates first trimester toll like receptor-2, supporting the role of PIF as an embryo derived factor influencing maternal innate immunity

RECEPTOR-2, SUPPORTING THE ROLE OF PIF AS AN EMBRYO DERIVED FACTOR INFLUENCING MATERNAL INNATE IMMUNITY MICHAEL PAIDAS, GRACIELA KRIKUN, LYNN BUCHWALDER, FREDERICK SCHATZ, KARL GODLEWSKI, EYTAN R. BARNEA, Yale University School of Medicine, Department Obstetrics, Gynecology and Reproductive Sciences, CoDirector, Yale Blood Center for Women and Children, New Haven, Connecticut, Yale University, Obstetrics and Gynecology & Reproductive Sciences, New Haven, Connecticut, UMDNJ/Robert Wood Johnson Medical School, CAMcare Health Center, Cherry Hill, New Jersey OBJECTIVE: Preimplantation factor (PIF), is a novel, embryo-derived, small peptide which appears very early in pregnancy. The maternal host response in pregnancy must allow for tolerance of the implanting embryo, and preservation of maternal defense mechanisms against viral and bacterial pathogens. We posit that: a) PIF may act as an immune modulating agent, capable of augmenting maternal defense mechanisms via upregulation of Toll-like receptor (TLR)-2, a transmembrane protein involved in pathogen recognition; b) PIF may will influence decidual cell (DC) production of interleukins (IL), metalloproteinases (MMP) involved in extracellular matrix degradation, and angiogenesis. STUDY DESIGN: DCs were obtained from women undergoing first trimester (TRI) elective terminations or third TRI repeat Cesarean sections. DCs were isolated, purified, and seeded on polystyrene tissue culture dishes. The effects of PIF on TLR-2 protein expression was carried out using first TRI DCs. Third TRI DCs were used to study the effects of PIF on well characterized markers of DC function, as measured by ELISA. Western blotting for TLR-2 and beta actin was conducted using established methods. Densitometric analyses were carried out with the Image J NIH analysis software. PIF (10nM) was used as an agonist to DC culture. Values were expressed as TLR2/beta actin ratio, correcting for total DNA content. RESULTS: PIF incubation was associated with a two-fold increase in TLR-2 expression. We were unable to detect any change in secreted levels of the following third TRI DC products: IL-6, IL-8, IL-11, plasminogen activator inhibitor-1, MMP-3, vascular endothelial growth factor. CONCLUSION: In this preliminary study, PIF significantly upregulates first trimester TLR-2 expression, suggesting that PIF may augment the maternal innate immune response. Maintainence of host defense mechanisms must occur as the host prepares to accept the implanting embryo. Further studies are needed to confirm PIF’s effects on TLR-2, evaluate downstream effects, and determine whether PIF regulates first TRI DC function.

Post-implantation mouse conceptuses produce paracrine signals that regulate the uterine endometrium undergoing decidualization

The uterus undergoes a series of dramatic changes in response to an implanting conceptus that, in some mammalian species, includes differentiation of the endometrial stroma into decidual tissue. This process, called decidualization, can be induced artificially in rodents indicating that the conceptus may not be essential for a proper maternal response in early pregnancy. In order to test this hypothesis, we determined if and how the conceptus affects uterine gene expression. We identified 5 genes ( Angpt1, Angpt2, Dtprp, G1p2 and Prlpa) whose steady-state levels in the uterus undergoing decidualization depends on the presence of a conceptus. In situ hybridization revealed region-specific effects which suggested that various components of the conceptus and more than one signal from the conceptus are likely responsible for altering decidual cell function. Using cell culture models we found that trophoblast giant cells secrete a type I interferon-like molecule which can induce G1p2 expression in endometrial stromal cells. Finally, decidual Prlpa expression was reduced in the uterus adjacent to Hand1- and Ets2-deficient embryos, suggesting that normal trophoblast giant cells in the placenta are required for the conceptus-dependent effects on Prlpa expression in the mesometrial decidua. Overall, these results provide support for the hypothesis that molecular signals from the mouse conceptus have local effects on uterine gene expression during decidualization.

Gene expression and specific binding of platelet-derived growth factor and its effect on DNA synthesis in human decidual cells

To clarify the biological significance of platelet-derived growth factor (PDGF) in human decidual cell function, which is important for the maintenance of pregnancy, we investigated gene expression of the PDGF subunits, PDGF-A and PDGF-B, specific binding of the PDGF isoform, and the effect of PDGF dimers on DNA synthesis in human decidual cells. We detected in decidua from early pregnancy the expected DNA bands of PDGF-A and PDGF-B by reverse transcriptase-polymerase chain reaction (RT-PCR) as well as mRNAs of each PDGF subunit by Northern blot hybridization, demonstrating that both PDGF subunits exist in this tissue. Scatchard plot analysis showed that decidual cells had both PDGF- α and PDGF- β receptors. PDGF-AA, -AB and -BB stimulated [ 3H]-thymidine incorporation in cultured decidual cells in a dose-dependent manner. These results indicate the importance of PDGF in human decidua.

Endothelin-1 regulates human decidual cells through both A- and B-type receptors

The aims of this study were to investigate the effects of endothelin-1 (ET-1) on first trimester human decidual cells, identify the ET receptor sub-types through which these effects are mediated and assess the role of cyclic AMP in any effects of ET-1. ET-1 increased prostaglandin production by first trimester decidual cells, which was consistent with similar studies in third trimester decidual cells. The endothelin A-type receptor (ET A) was coupled to the increased prostaglandin production from first trimester cells, as shown by the inhibitory effects of BQ610, an ET A receptor antagonist. The time course of this effect was unusual, with a rapid increase peaking after 6 h of stimulation, followed by a longer effect over 12–24 h, which was paralleled by changes in cyclic AMP production. No evidence was obtained for any involvement of cyclic AMP in mediating the effects of ET-1 on prostaglandin production. ET-1 also increased decidual prolactin production with a maximum effect after 6 h of stimulation. This was mediated through the ET B receptor and may be linked to increased cyclic AMP production, indicating that the ET A and ET B receptors were coupled to different second messenger systems and affected decidual cell function in different ways.

Decidual adenylate cyclase and prostaglandin production in vitro

Human decidua contains an active adenylate cyclase, and a number of studies indicate that adenylate cyclase is functionally linked to increased in vitro prostaglandin synthesis. Increased decidual prostaglandin synthesis is associated with parturition, and therefore activation of adenylate cyclase may be involved in the control of human parturition. In this study, third trimester human decidual cells were preincubated for no more than 24 h prior to stimulation with a number of reagents which increase cellular cyclic AMP levels. Forskolin rapidly increased intracellular and extracellular cyclic AMP levels, but there was no increase in prostaglandin E 2 biosynthesis during incubations ranging from 5 min up to 24 h. Dibutyryl cyclic AMP or 8-bromo-cyclic AMP were also without effect on PGE 2 production, which suggests that the adenylate cyclase was not linked to the mechanisms regulating prostaglandin production. Cholera toxin increased basal cyclic AMP and PGE 2 synthesis, and was without effect on IL-1β-stimulated PGE 2 levels. PGE 2 synthesis was increased by 24 h culture with IL-1β in all the cell preparations, indicating that the cells were biologically active, and that the lack of effect of changes in cyclic AMP synthesis on PGE 2 levels could not be attributed to a defect in the prostaglandin synthetic pathway. Our findings did not agree with earlier work which showed that changes in cyclic AMP were correlated with changes in PGE 2 production by human decidual cells. It is clear that in the previous studies the decidual cells were preincubated for 4–7 days prior to stimulation, in contrast with 24 h in our investigation. We suggest that the functional link between cyclic AMP and PGE 2 synthesis reported previously may develop during culture, and not be a part of normal decidual cell function, but further studies are needed to test this hypothesis.

Insulin-like growth factor regulation of human endometrial stromal cell function: coordinate effects on insulin-like growth factor binding protein-1, cell proliferation and prolactin secretion.

The insulin-like growth factor (IGF) autocrine/paracrine system is believed to be involved in endometrial differentiation, but there is limited information on the specific cellular functions regulated by IGFs in uterine tissues and their regulation of IGF-binding proteins (IGFBPs). We have investigated the regulation by insulin, IGF-I, and IGF-II, of IGFBP secretion in human endometrial stromal cells decidualized in vitro, and examined the interrelationship between the induced changes in IGFBP levels and the biological responses of stromal cells to IGFs. IGFBPs in conditioned media were analyzed by Western ligand blotting, and IGFBP-1 was quantified by an immunoenzymometric assay (IEMA). In the absence of peptides, decidualized stromal cells secreted 25.5 +/- 3.2 micrograms/day per 10(6) cells of IGFBP-1. Insulin caused a dose-dependent reduction of IGFBP-1 secretion (half-maximal inhibition at < 1 ng/ml) to a maximum of 1% of control values. Northern analysis using a specific cDNA probe showed the expression in decidualized stromal cells of a single 1.5 kb transcript for IGFBP-1, which was absent in insulin-treated cells. The effects of IGF-I and IGF-II on IGFBP-1 secretion were biphasic, with initial stimulation (200-250%) that peaked at 1 and 10 ng/ml, respectively, followed by inhibition at higher concentrations (half maximal inhibition at 3 ng/ml and 30 ng/ml, respectively). The decrease in IGFBP-1 levels in decidualized stromal cultures was associated with the induction of mitogenesis by IGF-I and IGF-II, while IGF effects on prolactin secretion paralleled those of IGFBP-1 secretion, with stimulation (243-324%) in the low concentration range followed by inhibition at higher concentrations. These data indicate that endometrial stromal cell IGFBP-1 is regulated by insulin, at concentrations that are compatible with insulin acting via its own receptor, while the effects of IGF-I and IGF-II on IGFBP-1 secretion, are suggestive of their acting probably through the type I IGF receptor. The present study describes distinct effects of the IGFs on stromal cell IGFBPs, that correlate with changes in the proliferative and secretory responses of decidualized stromal cells to the IGFs. Our findings suggest that complex IGF-IGFBP interactions may participate in the regulation of endometrial cell function, and support a role for IGF-II in stromal cell mitogenesis during decidualization, and as a local regulator of decidual cell function during the late secretory phase and early pregnancy.

Effect of RU 486 on the endometrial response to deciduogenic stimulus in ovariectomized rhesus monkeys treated with oestrogen and progesterone.

Using the artificial plaque--decidual cell model in rhesus monkeys, the potential role of progesterone in the process of of epithelial and stromal cell responses was investigated by time-adjusted application of an antiprogestin, RU 486. Epithelial plaque formation is an immediate response of the endometrium to either trauma or invading trophoblast cells. To study this process, RU 486 (2.5 mg/kg body weight) or vehicle (ethanol/saline, 7:3, v/v, i.m.) was administered to the first group of monkeys immediately following traumatization (days 16 and 17 of treatment cycle). Histometric analysis revealed that treatment with RU 486 led to significant inhibition (P less than 0.001) in the recruitment of epithelial cells into plaque acini and consequent reduction (P less than 0.001) in the spread of the plaque reaction compared with control monkeys. In the second group of monkeys, experimental treatment was delayed until plaque formation had occurred (days 21 and 22 of cycle). RU 486 induced increased degeneration (P less than 0.01) in plaque cells. Thus the transformation and the maintenance of the epithelial plaque response appears to be progesterone-dependent. Glandular epithelium showed only marginal changes (P less than 0.05) in maximum cell height, amount of pseudostratification and secretory activity of glands as a consequence of RU 486 treatment; however, the antiprogestin induced a higher incidence of glandular apoptosis (P less than 0.01 for both groups). It has been suggested that the higher degree of apoptosis in the glandular epithelium could be a consequence of the progesterone receptor blocking action of RU 486. No distinctive change in endothelial cell ultrastructure was evident following RU 486 treatment; however, venular diameter was significantly increased (P less than 0.01, group I; P less than 0.001, group II) along with an apparent reduction in the extent of oedema. There was increased extravasation (P less than 0.01) and leukocytic infiltration (P less than 0.001, group I; P less than 0.05, group II) following RU 486 treatment. RU 486 induced vascular responses and increased diapedesis could presumably have resulted from its progesterone blocking action in vascular cells. RU 486 accelerated the incidence (P less than 0.01) of stromal decidualization (group I), as well as quantitatively accentuating (P less than 0.001) the decidual cell reaction (group II). It is possible that RU 486 may inhibit specific functions of decidual cells, despite morphologically consistent decidual transformation.

Decidual cell function: evidence for a role in the regulation of serum CBG and a 60 kDa protein during early pregnancy in the hamster.

Several serum proteins increase in titer during pregnancy. We tested the hypothesis that decidual cells may signal the production of certain serum proteins in the hamster. Measurement of serum CBG by equilibrium binding using either [3H]-progesterone or [3H]-cortisol in conjection with ion exchange chromatography showed that decidualization increased CBG levels. Two-dimensional gel electrophoresis revealed that a 60 kDa++ protein increases markedly in the serum of the hormonally pseudopregnant (PSP) animal soon after artificial induction of decidualization on PSP day 4. The 60 kDa serum protein remains low in the nondecidualized PSP animal, but it increases in the pregnant animal. A photoaffinity labeling procedure was used to covalently bind [3H]-androstadienolone to CBG. Fluorography of 2D gels run under denaturing conditions established that the 60 kDa protein did not bind steroid as did CBG (69 kDa). To determine whether decidual cells could induce the 60 kDa and CBG proteins, different numbers of decidual cells were injected IP into PSP recipients. A single injection of 50 x 10(6) decidual cells induced both serum proteins within 48h, whereas the same number of hamster fetal cells was ineffective. Thus, these results demonstrate that hamster decidual cells induce a 60 kDa protein of unknown function and serum CBG. Since the decidual cell itself does not appear to be the source of either protein, it follows that the decidual cell signals the synthesis and secretion of these proteins elsewhere in the body, most likely in the liver. To our knowledge, this is the first demonstration that the decidual cell regulates serum CBG and other proteins in this manner.

Life History of Decidual Cells: A Review*

Decidual cells are a distinctive cell population observed in the mammalian endometrium during pregnancy. Their appearance can also be induced with appropriate stimuli in the hormone-primed pseudopregnant uterus. This review deals with their life history, including the dynamic morphological events during the process of decidualization, cytochemical markers for decidual cell reaction, the surface markers and functions of decidual cells, and, finally, the origin and fate of this cell class. The recent discovery of the bone marrow origin of decidual cell precursors adds a new dimension to decidual cell biology. Future studies of steps in the differentiation of the decidual cell lineage await the identification of unique lineage-specific cell--surface of cytoplasmic marker(s); a precise knowledge of decidual cell functions can only be obtained from a discriminating analysis using purified cell populations.