The Effect of Gossypol and Misoprostol on Luteal and Decidual Cells in Vitro

Gossypol and Misoprostol could directly damage the luteal and decidual cells cultured in vitro. The LD50 of gossypol alone to luteal and decidual cells were 1.27±0.09 μg/ml and 3.06±0.23 μg/ml, respectively; however when combined with misoprostol (to luteal cells 5μg/ml, or to decidual cells 10μg/ml), the LD50 of gossypol signifcantly decreased to 0.89±0.25 μg/ml and 1.88±0.26 μg/ml, respectively. The LD50 of misoprostol alone to luteal and decidual cells were 14.29±1.29μg/ml and 24.37±4.49 μg/ml, respectively; but it decreased to 8.79±2.18 μg/mland 17.29±1.56 μg/ml, respectively when combined with gossypol (to luteal cells 0.5 μg/ml, or to decidual cells 1.0 μg/ml), also showing statistical difference. The results suggested that the combination of gossypol with misoprostol had synergistic effect on the degeneration of luteal and decidual cells in vitro.

Modulation of the Culture Supernatant of Decidual Cells with Exogenous Cytokines on Killing Activity of Natural Killer Cells in Early Pregnancy

To investigate the important function of cytokines in early pregnancy and to provide basic and experimental evidence for understanding the mechanism of their action. Methods Add interferon γ(IFN γ),interleukin 2(IL 2), interleukin 6(IL 6) and epidermal growth factor(EGF) to the confluent culturing decidual cells with three different concentrations and harvest the culture supernatant after 12, 24 and 48 h separately. Observe the effect of the supernatant on killing activity of NK cells with radioimmunological assay of 51 Cr immersion. Results The culture supernatant of decidual cells can promote the killing activity of NK cells in various degrees, and the effect is independent of the type, concentration and acting time of cytokines. Conclusion In normal pregnancy, decidual cytokine network is in a dynamic equilibrium. Exogenous cytokines would be harm to normal pregnancy by interfering the equilibrium state, but the exact mechanism needs further study.

Effect of IFN-γ/IL-10 on IL-10 Receptor Expression of Human Decidual Stromal Cells in Early Pregnancy

Objective To study the role of IFN-γ/IL-10 cytokines protein expression of human decidual stromal cells（DSC） vitro. on IL-10 receptor gene and in human early pregnancy in vitro. Methods Human DSC was isolated and cultured in vitro, and the expression of IL-10R1 and IL-10R2 gene was analyzed after cells had been treated with TH2-type cytokines IL-10 and TH1-type cytokines IFN-γ within 60 rain with semiquantitative reverse transcriptase-PCR, then the influence of IL-10 and IFN-γ on expression of IL-10R protein was examined by first trimester DSC using flow cytometry. In addition, the vitality of DSC was detected by MTT. Results IL-10R1 mRNA levels of DSC treated with IL-10 （10 ng/ml） reached the peak level within 15 rain, and were significantly lower at 30 rain, then were not detected at 45 min. The expression of IL-10R1 were induced to moderate level by IFN-γ（10 ng/ml） within 30 rain, and reduced to undetected levels at 60 min. There was no significant difference of IL-10R2 expression （P〉0.05） between treated and not with the abovementioned cytokines. The IL-10R protein expression and vitality of DSC were significantly enhanced by IL-10 （10 ng/ml） and IFN-γ （10 ng/ml） which treated DSC 48 h （P〈0.05）. Coneclusion IL-10 and IFN-γ may play an important role of biologic function in early pregnancy by influencing IL-10R expression of DSC.

Co-Culture of Early Embryo with Human Decidual Stromal Cells in vitro by Improvement of Early Embryo Development

Summary: An early embryo co-culture system with human decidual stromal cells was established to study its effect on early embryonic cleavage and growth in vitro. Three hundred and eight 2-cell mouse embryos were co-cultured with human decidual stromal cell monolayer in MEM+0. 4 % bovine serum albumin (BSA) and 163 embryos cultured in MEM+15 % FCS alone as control. Among the mouse 2-cell embryos co-cultured with human decidual stromal cells, 72.73 % developed to the morula stage and 67.21 % cavitated to blastocysts with 59. 74 % hatching, as compared with 61. 34 % to morula stage, 48. 47 % to blastocysts and none hatching in the controls, respectively. Co-cultured embryos cleaved slightly faster than controls and showed no or less fragmentation than those in the control. These results suggested that human decidual stromal cells can support early embryonic development and yield a reasonable number of embryos with good quality up to blastocyst stage.

Decidual Natural Killer Cells Are Essential for a Successful Pregnancy (Review)

Pregnancy is a complex physiological process involving several interconnected systems. Many researchers were concerned that the formation of a fetus with different genetic components may contradict the normal state of immunity, which attempts to reject and fight foreign bodies. This piqued the interest of biologists and immunologists, who set out to discover the immune system’s composition and mode of response in the uterus. According to several studies, natural killer (NK) cells are present in a significant percentage that differs from what is seen in peripheral blood. As a result, several scientific studies have been conducted on uterine NK cells, investigating their types, characteristics, receptors, secretions, and interactions with the surrounding environment. Research has also indicated the capacity of uterine NK cells to strike a balance between eradicating uterine infections and effectively contributing to different phases of pregnancy. Various studies have shown that NK cell activity is intimately related to the success or failure of pregnancy. In this review, we describe the uterine NK cell subtypes;decidual (dNK) cells and endometrial NK cells (eNK) cells and their important role during different phases of pregnancy.

PiggyBac transposon-mediated gene delivery efficiently generates stable transfectants derived from cultured primary human deciduous tooth dental pulp cells(HDDPCs) and HDDPC-derived iPS cells

The ability of human deciduous tooth dental pulp cells（HDDPCs） to differentiate into odontoblasts that generate mineralized tissue holds immense potential for therapeutic use in the field of tooth regenerative medicine. Realization of this potential depends on efficient and optimized protocols for the genetic manipulation of HDDPCs. In this study, we demonstrate the use of a Piggy Bac（PB）-based gene transfer system as a method for introducing nonviral transposon DNA into HDDPCs and HDDPC-derived inducible pluripotent stem cells. The transfection efficiency of the PB-based system was significantly greater than previously reported for electroporation-based transfection of plasmid DNA. Using the neomycin resistance gene as a selection marker, HDDPCs were stably transfected at a rate nearly 40-fold higher than that achieved using conventional methods. Using this system, it was also possible to introduce two constructs simultaneously into a single cell. The resulting stable transfectants, expressing td Tomato and enhanced green fluorescent protein, exhibited both red and green fluorescence. The established cell line did not lose the acquired phenotype over three months of culture. Based on our results, we concluded that PB is superior to currently available methods for introducing plasmid DNA into HDDPCs. There may be significant challenges in the direct clinical application of this method for human dental tissue engineering due to safety risks and ethical concerns. However, the high level of transfection achieved with PB may have significant advantages in basic scientific research for dental tissue engineering applications, such as functional studies of genes and proteins. Furthermore, it is a useful tool for the isolation of genetically engineered HDDPC-derived stem cells for studies in tooth regenerative medicine.

Stem cells from human exfoliated deciduous teeth ameliorate concanavalin A-induced autoimmune hepatitis by protecting hepatocytes from apoptosis

BACKGROUND Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide,which emphasizes the urgent need to identify novel treatments.Stem cells from human exfoliated deciduous teeth(SHED),which are easy to obtain in a non-invasive manner,show pronounced proliferative and immunomodulatory capacities.AIM To investigate the protective effects of SHED on concanavalin A(ConA)-induced hepatitis in mice,and to elucidate the associated regulatory mechanisms.METHODS We used a ConA-induced acute hepatitis mouse model and an in vitro co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis,as well as the associated underlying mechanisms.RESULTS SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3+,CD4+,tumor necrosis-alpha+,and interferon-gamma+inflammatory cells.Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice.SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations.Mechanistically,ConA upregulated tumor necrosisalpha and interferon-gamma expression,which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis,resulting in acute liver injury.SHED administration protected hepatocytes from ConA-induced apoptosis.CONCLUSION SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway.Our findings could provide a potential treatment strategy for hepatitis.

Application of dental stem cells in three-dimensional tissue regeneration

Dental stem cells can differentiate into different types of cells.Dental pulp stem cells,stem cells from human exfoliated deciduous teeth,periodontal ligament stem cells,stem cells from apical papilla,and dental follicle progenitor cells are five different types of dental stem cells that have been identified during different stages of tooth development.The availability of dental stem cells from discarded or removed teeth makes them promising candidates for tissue engineering.In recent years,three-dimensional(3D)tissue scaffolds have been used to reconstruct and restore different anatomical defects.With rapid advances in 3D tissue engineering,dental stem cells have been used in the regeneration of 3D engineered tissue.This review presents an overview of different types of dental stem cells used in 3D tissue regeneration,which are currently the most common type of stem cells used to treat human tissue conditions.

Decidual stromal cells recruit Th 17 cells into decidua to promote proliferation and invasion of human trophoblast cells by secreting IL-17

T helper 17 （Th17） cells have both regulatory and protective roles in physiological conditions. The Th17 subset and the cytokine interleukin-17A （IL-17A） have been implicated in the pathogenesis of certain autoimmune diseases, several types of cancer and allograft rejection. However, the role of Th17 cells at the maternal/fetal interface remains unknown. Here, we demonstrate that Th17 cells are present in decidua and are increased in the peripheral blood of 10 clinically normal pregnancies based on intracellular cytokine analysis. Our results suggest a potential role of Th17 cells in sustaining pregnancy in humans. Furthermore, we demonstrate that decidual stromal cells （DSCs） but not trophoblast cells recruit peripheral Th17 cells into the decidua by secreting CCL2. The recruited Th17 cells promote proliferation and invasion and inhibit the apoptosis of human trophoblast cells by secreting IL-17 during the first trimester of pregnancy. These findings indicate a novel role for Th17 cells in controlling the maternal-fetal relationship and placenta development.

Cyclooxygenase-2 and Decidual Immune Cells

Cyclooxygenase-2(COX-2)is a rate-limiting enzyme in arachidonic acid(AA)metabolism.COX-2 and its products(prostanoids)serve versatile biological functions during pregnancy.Numerous evidences demonstrate special reprogramming of COX-2-catalyzing AA metabolism in decidual immune cells(DICs),particularly in decidual macrophages,corresponding to special gestational phases.This review summarizes the reprogramming of COX-2-catalyzing AA metabolism in DICs as well as the immunoregulation of diverse COX-2-generating prostanoids in DICs during the different phases of gestation.

Effect of Contragestazolin(L14105) on Pregnancy Termination in Rodents

Contragestazolin (L14105) belongs to the class of 2 phenyl triazole isoquinolines. When given subcutaneously, intramuscularly or orally showed potential pregnancy terminating activity in mice, rats, hamsters and guinea pigs, but the dialy doses of oral administration needed were 7.1, 6.3 and 47.6 times (for mouse, rat and hamster) greater than those needed parenterally. L14105 had low affinity to rat uterine progesterone receptor. When cultured human decidual cells were exposed to L14105 0.077～0.155 mmol/L for 24～48 h, the cells' viability markedly dropped and structural changes occurred in comparison with controls. Histological examination of conceptuses of rats showed edema, degeneration, necrosis and atrophy or disappearance of decidual cells nuclei and absorption of embryos after the sc administration of L14105 5 mg/kg for 24～48 h. L14105 stimulated the contractile force of uterine smooth muscle in vivo or in vitro. Conclusion: L14105 shows a very high pregnancy terminating activity. Multiple oral administration is also effective. The mode of action of contragestation is related to damage of decidual cells and stimulation of uterine contractility.

A Defective CXCL16/CXCR6 Axis Increases the Risk of Pregnancy Loss via the Abnormal Crosstalk between Decidual γδ T Cells and Trophoblasts

Objective::The maternal-fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus.The interaction between decidualγδT cells and trophoblasts plays a pivotal role during successful pregnancy;however,their physiological functions in early-term human pregnancy are still not completely illustrated.This study was undertaken to illustrate the functional roles of CXCL16/CXCR6 to prevent pregnancy loss via the crosstalk between decidualγδT cells and HTR8/SVneo trophoblast cells.Methods::The percentile of CXCR6+γδT cells in the peripheral blood from normal female and recurrent spontaneous abortion(RSA)patients was analyzed by flow cytometry.The expression of CXCR6 was detected in decidual immune cells via flow cytometry,and the expression of CXCL16 was analyzed in HTR8/SVneo trophoblast cells and lentivirus(LV)-HTR8/SVneo trophoblast cells via enzyme-linked immunosorbent assay.Reverse transcriptase-polymerase chain reaction was used to verify the expression of the CXCL16 gene in LV-HTR8/SVneo trophoblast cells.Expression of granzyme B and cytokines and proliferation of decidualγδT cocultured with HTR8/SVneo trophoblast cells were analyzed by flow cytometry.Invasion of HTR8/SVneo trophoblast cells was assessed via Matrigel transwell assay.Adoptive transfer was induced in vivo further to illustrate that the normal expression of CXCL16/CXCR6 could prevent pregnancy loss.Results::The percentile of CXCR6+γδT cells in the peripheral blood from RSA patients was lower than normal pregnancies.The expression of CXCR6 was highest in the decidualγδT cells among decidual immune cells,and the expression of CXCL16 increased as the amount of HTR8/SVneo trophoblast cells increased.Expression of granzyme B in the decidualγδT cells was downregulated by cocultured with HTR8/SVneo cells dependent of CXCL16,and HTR8/SVneo trophoblast cells induced the Th2 cytokines production in the decidualγδT cells.Both the expression of CXCR6 in the decidualγδT cells and proliferation of the decidualγδT cells were promoted by HTR8/SVneo trophoblast cells.On the other hand,decidualγδT cells enhanced the invasion of HTR8/SVneo trophoblast cells and thus promoted embryo implantation.In vivo study was taken further and shown that low expression of CXCL16/CXCR6 results in pregnancy loss because of dialog disorder between decidualγδT cells and trophoblasts.Conclusions::Low expression of CXCL16/CXCR6 results in pregnancy loss because of the dialog disorder between decidualγδT cells and trophoblasts,and it showed a light on the effective strategy of adoptive transfer of CXCR6+γδT cells on the treatment of RSA.This observation provides a scientific basis on which a potential strategy can be applied to the early-detect and treatment of RSA.

Role of Decidual Natural Killer Cells at the Maternal-Fetal Interface during Pregnancy

Pregnancy is a complicated process with intricate cell-to-cell crosstalk and immune regulation.Decidual natural killer(NK)cells account for 50%-70% of decidual immune cells in early pregnancy,suggesting that they play important roles in various events,such as embryo implantation and vascular remodeling.Many studies have shown that decidual NK cells interact with other cells either through direct contact or the secretion factors such as cytokines and chemokines.Hence,this review aimed to present the phenotypic characteristics,classification,and functions of decidual NK cells at the maternal-fetal interface during pregnancy.

Role of maternal-fetal immune tolerance in the establishment and maintenance of pregnancy

Normal pregnancy is a contradictory and complicated physiological process.Although the fetus carries the human leukocyte antigen(HLA)inherited from the paternal line,it does not cause maternal immune rejection.As the only exception to immunological principles,maternal-fetal immune tolerance has been a reproductive immunology focus.In early pregnancy,fetal extravillous trophoblast cells(EVTs)invade decidual tissues and come into direct contact with maternal decidual immune cells(DICs)and decidual stromal cells(DSCs)to establish a sophisticated maternal-fetal crosstalk.This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal-fetal tolerance based on maternal-fetal crosstalk.Insights into maternal-fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion,pre-eclampsia,and premature birth.

Comparison of Osteogenesis Between Two Kinds of Stem Cells from Goat Combined Calcium Phosphate Cement in Tissue Engineering

To explore the possible mechanism of osteogenesis for deciduous teeth stem cells (DTSCs) in vivo/ vitro, stem cells from goat deciduous teeth (SGDs) were firstly isolated, induced and transplanted into immunocompromised mice. The SGDs's mineralization pattern and osteogenesis were compared with bone marrow messenchymal stem cells (BMMSCs) from goats. SGDs have similar osteogenic differentiation pattern in vitro and bone-like tissue formation mechanism in vivo to BMMSCs; moreover SGDs have stronger alkaline phosphatase (ALP) gene expression and osteopontin (OPN) gene expression levels than BMMSCs; also SGDs can form more bone-like tissues than BMMSCs when cell-scaffold compounds are transplanted into immunocompromised mice. This pre-clinical study in a large-animal model confirms that DTSCs may be an appropriate source of stem cells in repairing bone defects with tissue engineering.

Decidualization and Related Pregnancy Complications

Decidualization is the differentiation of endometrial stromal cells into secretory decidual stromal cells.Human decidualization involves some amount of signaling molecules and pathways as well as genetic reprogramming,which is driven by the postovulatory rise in progesterone levels and local cyclic adenosine monophosphate production.Decidualization extends from the primary decidual zone to the secondary decidual zone,and then exits through apoptosis.Evidences support that decidual fibroblasts function as the pool of decidual stromal cells during pregnancy.Decidualization undergoes an acute inflammatory phase,an anti-inflammatory secretory phase to the final recession phase.The decidualization of the inner layer of endometrium,termed decidua,is the most critical determinant of pregnancy success,which can promote placenta formation,modulate immune tolerance,foster resistance to oxidative stress,sense embryo quality,and control labor.Failure to adequate decidualization in terms of hormones,biochemistry,and immunology leads to adverse pregnancy outcomes,including diseases such as preeclampsia,miscarriage,premature labor,repeated implantation failures,and some age-related decline in reproductive capacity.The development of animal models and in vitro culture systems combined with emerging technologies provides a powerful system to explore the mechanism of decidualization.However,decidualization is a dynamic,multi-step process,and translating of current research progress into disease predictions and interventions for pregnancy complications remains to be achieved.The study of periodic regeneration and spontaneous decidualization of the endometrium will be beneficial to the diagnosis and treatment of pregnancy diseases.

SHED-derived exosomes ameliorate hyposalivation caused by Sjögren’s syndrome via Akt/GSK-3b/Slug-mediated ZO-1 expression

Background:Sjögren’s syndrome(SS)is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations.The treatment is still challenging.This study aimed to explore the therapeutic role and mechanism of exosomes obtained from the supernatant of stem cells derived from human exfoliated deciduous teeth(SHED-exos)in sialadenitis caused by SS.Methods:SHED-exos were administered to the submandibular glands(SMGs)of 14-week-old non-obese diabetic(NOD)mice,an animal model of the clinical phase of SS,by local injection or intraductal infusion.The saliva flow rate was measured after pilocarpine intraperitoneal injection in 21-week-old NOD mice.Protein expression was examined by western blot analysis.Exosomal microRNA(miRNAs)were identified by microarray analysis.Paracellular permeability was evaluated by transepithelial electrical resistance measurement.Results:SHED-exos were injected into the SMG of NOD mice and increased saliva secretion.The injected SHED-exos were taken up by glandular epithelial cells,and further increased paracellular permeability mediated by zonula occluden-1(ZO-1).A total of 180 exosomal miRNAs were identified from SHED-exos,and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)pathway might play an important role.SHED-exos treatment down-regulated phospho-Akt(p-Akt)/Akt,phospho-glycogen synthase kinase 3b(p-GSK-3b)/GSK-3b,and Slug expressions and up-regulated ZO-1 expression in SMGs and SMG-C6 cells.Both the increased ZO-1 expression and paracellular permeability induced by SHED-exos were abolished by insulin-like growth factor 1,a PI3K agonist.Slug bound to the ZO-1 promoter and suppressed its expression.For safer and more effective clinical application,SHED-exos were intraductally infused into the SMGs of NOD mice,and saliva secretion was increased and accompanied by decreased levels of p-Akt/Akt,p-GSK-3b/GSK-3b,and Slug and increased ZO-1 expression.Conclusion:Local application of SHED-exos in SMGs can ameliorate Sjögren syndrome-induced hyposalivation by increasing the paracellular permeability of glandular epithelial cells through Akt/GSK-3b/Slug pathway-mediated ZO-1 expression.

Human dNK cell function is differentially regulated by extrinsic cellular engagement and intrinsic activating receptors in first and second trimester pregnancy

Decidual natural killer （dNK） cells express an array of activation receptors to regulate placental immunity and development during early pregnancy. We investigated the functional character of human dNK cells during the first and second trimester of gestation and the interaction between dNK and trophoblast cells. Although the frequency of CD56＋CD16-dNK among the total CD45＋ leukocytes did not change over this period, the expression of the activating receptors, NKp80 and NKG2D, was greatly upregulated. We observed a significantly higher number of extravillous trophoblast cells in proximity to the dNK cells in the first trimester in comparison with the second trimester decidua. NKG2D expression by first trimester dNK cells was decreased when co-cultured with the HTR-8 trophoblast cell line. In the second trimester, functional markers of dNK activation, i.e., angiogenic factor production （e.g., vascular endothelial growth factor, interleukin-8, interferon-gamma）, remained stable despite an increase in NKp80 or NKG2D surface expression. Furthermore, the degranulation capacity of dNK cells, as assessed by CD107a, was decreased in the second trimester. We suggest that in the first trimester, trophoblast-dNK interactions generate a population of dNK cells with a suppressed activating phenotype. In the second trimester, the loss of trophoblast-dNK interactions led to the inhibition of dNK cell function, although their activating receptor expression was increased. We speculate that during pregnancy, two mechanisms operate to modulate the dNK cell activation：suppression of activating receptor levels in the first trimester by trophoblasts and disengagement of receptor-ligand coupling in the second trimester.

Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration

Exosomes derived from mesenchymal stem cells(MSCs)have demonstrated regenerative potential for cell-free bone tissue engineering,nevertheless,certain challenges,including the confined therapeutic potency of exosomes and ineffective delivery method,are still persisted.Here,we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth(SHEDs)via comprehensive proteomics analysis,and the corresponding hypoxic exosomes(H-Exo)exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion,VEGF signaling pathway,and thyroid hormone synthesis.Then,we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection.This platform is based on a simple adsorbing technique,where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide)(PLGA)microspheres with bioinspired polydopamine(PDA)coating(PMS-PDA microspheres).The PMS-PDA microspheres could effectively adsorb exosomes,show sustained release of H-Exo for 21 days with high bioactivity,and induce vascularized bone regeneration in 5-mm rat calvarial defect.These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration,hence facilitating the clinical translation of exosome-based therapy.

Immune Regulation at Maternal-fetal Interface in Early Pregnancy

Decidual immune cells(DICs),including T-cells,regulatory T-cells,macrophages/dendritic cells,natural killer cells,and neutrophils,are resident at the maternal-fetal interface,and play vital roles in regulating trophoblast migration,decidual angiogenesis,immune tolerance,placentation,and decidualization during the early pregnancy.Extensive researches have revealed that these maternal DICs cooperated with each other,or with maternal decidual stromal cells,or with fetal-derived trophoblasts,and further formed a special maternal-fetal cross talk at the maternal-fetal interface,which was essential for the construction and maintenance of physiological pregnancy.Once aberrant cross talk and immune regulation arise,many pregnancy complications will inevitably occur,such as spontaneous abortion,intrauterine growth restriction(IUGR),preeclampsia(PE),and preterm birth.Here,we reviewed how critical immune cells are either enriched or excluded from the decidua,how their function is regulated within the decidua,and how they variously contribute to pregnancy success or failure.