Objective:Structural abnormalities and dysfunction of the placenta contribute to pregnancy-related complications,such as preeclampsia.Syncytin-A(synA)has been reported to be expressed in the placenta.The contribution ...Objective:Structural abnormalities and dysfunction of the placenta contribute to pregnancy-related complications,such as preeclampsia.Syncytin-A(synA)has been reported to be expressed in the placenta.The contribution of synA to developmental abnormalities and dysfunction of the placenta remains elusive.In this study,we aimed to explore the role of synA in placental development and functions.Methods:SynA-knockout mice were generated using the CRISPR-Cas9 method,and the phenotypes of the placenta and fetus ofsynA-knockout mice were observed.Real-time quantitative polymerase chain reaction(PCR)and routine PCR were employed to detect the genotypes of the offspring.CD31 immunohistochemistry was used to evaluate the vessel density of the placenta,and the protein levels of key molecules were measured by western blotting.Results:SynA knockout caused fetal death.Furthermore,synA-knockout mice showed placental developmental abnormalities,indicated by a thinner labyrinth layer,thicker spongiotrophoblast layer,lower blood vessel density,and significantly higher numbers of apoptotic trophoblasts,when compared with wild-type littermates.Mechanistically,synA ablation induced apoptosis-inducing factor(AIF)cleavage and nuclear localization and promoted placental trophoblast apoptosis.In addition,synA knockout increased the calpain1 protein levels.The calpain1 inhibitor calpeptin blockedsynA knockout-induced AIF cleavage,partially restoring the placental structural abnormalities ofsynA-knockout mice.Conclusions:SynA knockout leads to placental developmental abnormalities by inducing trophoblastic apoptosis via the calpain1-AIF pathway.展开更多
This study aimed to estimate the risk of venous thromboembolism(VTE),arterial thromboembolism(ATE),and other side effects following the use of drospirenone(DRSP)-containing combined oral contraceptives(COCs).When comp...This study aimed to estimate the risk of venous thromboembolism(VTE),arterial thromboembolism(ATE),and other side effects following the use of drospirenone(DRSP)-containing combined oral contraceptives(COCs).When compared with non-DRSP-containing COCs,DRSP-containing COCs decreased the risk of VTE by 15%in the overall study population,although this was not statistically significant(adjusted hazard ratio/risk ratio[95%confidence interval]0.85[0.69,1.04]).DRSP-containing COCs also showed significant benefits in terms of ATE risk.The body mass index of the subjects significantly decreased by 0.64 kg/m^(2) after taking the DRSP-containing COCs for 6 months.We concluded that DRSP-containing COCs were safe for use and could be broadly recommended.展开更多
文摘Objective:Structural abnormalities and dysfunction of the placenta contribute to pregnancy-related complications,such as preeclampsia.Syncytin-A(synA)has been reported to be expressed in the placenta.The contribution of synA to developmental abnormalities and dysfunction of the placenta remains elusive.In this study,we aimed to explore the role of synA in placental development and functions.Methods:SynA-knockout mice were generated using the CRISPR-Cas9 method,and the phenotypes of the placenta and fetus ofsynA-knockout mice were observed.Real-time quantitative polymerase chain reaction(PCR)and routine PCR were employed to detect the genotypes of the offspring.CD31 immunohistochemistry was used to evaluate the vessel density of the placenta,and the protein levels of key molecules were measured by western blotting.Results:SynA knockout caused fetal death.Furthermore,synA-knockout mice showed placental developmental abnormalities,indicated by a thinner labyrinth layer,thicker spongiotrophoblast layer,lower blood vessel density,and significantly higher numbers of apoptotic trophoblasts,when compared with wild-type littermates.Mechanistically,synA ablation induced apoptosis-inducing factor(AIF)cleavage and nuclear localization and promoted placental trophoblast apoptosis.In addition,synA knockout increased the calpain1 protein levels.The calpain1 inhibitor calpeptin blockedsynA knockout-induced AIF cleavage,partially restoring the placental structural abnormalities ofsynA-knockout mice.Conclusions:SynA knockout leads to placental developmental abnormalities by inducing trophoblastic apoptosis via the calpain1-AIF pathway.
文摘This study aimed to estimate the risk of venous thromboembolism(VTE),arterial thromboembolism(ATE),and other side effects following the use of drospirenone(DRSP)-containing combined oral contraceptives(COCs).When compared with non-DRSP-containing COCs,DRSP-containing COCs decreased the risk of VTE by 15%in the overall study population,although this was not statistically significant(adjusted hazard ratio/risk ratio[95%confidence interval]0.85[0.69,1.04]).DRSP-containing COCs also showed significant benefits in terms of ATE risk.The body mass index of the subjects significantly decreased by 0.64 kg/m^(2) after taking the DRSP-containing COCs for 6 months.We concluded that DRSP-containing COCs were safe for use and could be broadly recommended.