t Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus.Disorders in this process are tightly associated with adverse pregnancy o...t Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus.Disorders in this process are tightly associated with adverse pregnancy outcomes including recurrent miscarriage(RM).However,an indepth understanding of the systematic and decidual immune environment in RM remains largely lacking.In this study,we utilized single-cell RNA-sequencing(scRNA-seq)to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and unexplained RM pregnancies at the early stage of gestation.Integrative analysis identifies 22 distinct cell clusters in total,and a dramatic difference in leukocyte subsets and molecular properties in RM cases is revealed.Specifically,the cytotoxic properties of CD8^(+)effector T cells,nature killer(NK),and mucosal-associated invariant T(MAIT)cells in peripheral blood indicates apparently enhanced pro-inflammatory status,and the population proportions and ligand–receptor interactions of the decidual leukocyte subsets demonstrate preferential immune activation in RM patients.The molecular features,spatial distribution,and the developmental trajectories of five decidual NK(dNK)subsets have been elaborately illustrated.In RM patients,a dNK subset that supports embryonic growth is diminished in proportion,while the ratio of another dNK subset with cyto toxic and immune-active signature is significantly increased.Notably,a unique pro-inflammatory CD56^(+)CD16^(+)dNK subset substantially accumulates in RM decidua.These findings reveal a comprehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy and provide an in-depth insight into the immune pathogenesis for early pregnancy loss.展开更多
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, respectivel...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.展开更多
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 ...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.展开更多
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...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.展开更多
基金the National Key R&D Program of China(Grant Nos.2018YFC1004100,2017YFC1001404,2016YFC1000401,and 2016YFC1000200)the National Natural Science Foundation of China(Grant Nos.81730040and 81490740)。
文摘t Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus.Disorders in this process are tightly associated with adverse pregnancy outcomes including recurrent miscarriage(RM).However,an indepth understanding of the systematic and decidual immune environment in RM remains largely lacking.In this study,we utilized single-cell RNA-sequencing(scRNA-seq)to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and unexplained RM pregnancies at the early stage of gestation.Integrative analysis identifies 22 distinct cell clusters in total,and a dramatic difference in leukocyte subsets and molecular properties in RM cases is revealed.Specifically,the cytotoxic properties of CD8^(+)effector T cells,nature killer(NK),and mucosal-associated invariant T(MAIT)cells in peripheral blood indicates apparently enhanced pro-inflammatory status,and the population proportions and ligand–receptor interactions of the decidual leukocyte subsets demonstrate preferential immune activation in RM patients.The molecular features,spatial distribution,and the developmental trajectories of five decidual NK(dNK)subsets have been elaborately illustrated.In RM patients,a dNK subset that supports embryonic growth is diminished in proportion,while the ratio of another dNK subset with cyto toxic and immune-active signature is significantly increased.Notably,a unique pro-inflammatory CD56^(+)CD16^(+)dNK subset substantially accumulates in RM decidua.These findings reveal a comprehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy and provide an in-depth insight into the immune pathogenesis for early pregnancy loss.
文摘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.
文摘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.
文摘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.
