Poor oocyte quality is associated with early embryo developmental arrest and infertility.Maternal gene plays crucial roles in the regulation of oocyte maturation,and its mutation is a common cause of female infertilit...Poor oocyte quality is associated with early embryo developmental arrest and infertility.Maternal gene plays crucial roles in the regulation of oocyte maturation,and its mutation is a common cause of female infertility.However,how to improve oocyte quality and develop effective therapy for maternal gene mutation remains elusive.Here,we use Zar1 as an example to assess the feasibility of genome transfer to cure maternal gene mutationecaused female infertility.We first discover that cytoplasmic deficiency primarily leads to Zar1-null embryo developmental arrest by disturbing maternal transcript degradation and minor zygotic genome activation(ZGA)during the maternal-zygotic transition.We next perform genome transfer at the oocyte(spindle transfer or polar body transfer)and zygote(early pronuclear transfer or late pronuclear transfer)stages to validate the feasibility of preventing Zar1 mutationecaused infertility.We finally demonstrate that genome transfer either at the oocyte or at the early pronuclear stage can support normal preimplantation embryo development and produce live offspring.Moreover,those pups grow to adulthood and show normal fertility.Therefore,our findings provide an effective basis of therapies for the treatment of female infertility caused by maternal gene mutation.展开更多
Assisted reproductive technology(ART)is associated with increased implantation failure and subsequent metabolic abnormalities in offspring,but the underlying mechanisms remain largely elusive.Here,we reveal that persi...Assisted reproductive technology(ART)is associated with increased implantation failure and subsequent metabolic abnormalities in offspring,but the underlying mechanisms remain largely elusive.Here,we reveal that persistent Wnt signaling during the peri-implantation stage may be a key obstacle to the implantation of in vitro fertilization(IVF)embryos in a mouse model.Wnt activation affects the deposition of H3K27ac and H3K27me3 on pluripotency genes and bivalent genes,respectively,leading to the abnormal naïve-primed transition and suppressing expression of Otx2 in the epiblast.Furthermore,treatment with the Wnt inhibitor IWP2 promotes the redistribution of histone modifications and gene expression of epiblast.Importantly,Wnt inhibiting significantly improves implantation and intrauterine development of IVF embryos and subsequently ameliorates offspring metabolic abnormalities.Moreover,Wnt inhibiting markedly improves human peri-implantation embryo development and facilitates the transition from a naïve pluripotency state.Our study reveals a novel mechanism underlying the prevention of IVF embryo implantation failure and metabolic disorders in offspring.展开更多
Aluminum ions produced by aluminum mining,electrolytic industry and aluminum-based coagulants can enter wastewater treatment plants and interact with activated sludge.They can subsequently contribute to the removal of...Aluminum ions produced by aluminum mining,electrolytic industry and aluminum-based coagulants can enter wastewater treatment plants and interact with activated sludge.They can subsequently contribute to the removal of suspended solids and affect activated sludge flocculation,as well as nitrogen and phosphorus removal.In this study,the effects of Al^3+on pollutant removal,sludge flocculation and the composition and structure of extracellular polymeric substances(EPS)were investigated under anaerobic,anoxic and oxic conditions.Results demonstrated that the highest chemical oxygen demand(COD)and total nitrogen(TN)removal efficiencies were detected for an Al^3+concentration of 10 mg/L.In addition,the maximal dehydrogenase activity and sludge flocculation were also observed at this level of Al^3+.The highest removal efficiency of total phosphorus(TP)was achieved at an Ar+concentration of30 mg/L.The flocculability of sludge in the anoxic zone was consistently higher than that in the anaerobic and oxic zones.The addition of Al^3+promoted the secretion of EPS.Tryptophan-like fluorescence peaks were detected in each EPS layer in the absence of Al^3+.At the Al^3+concentration of 10 mg/L,fulvic acid and tryptophan fluorescence peaks began to appear while the majority of protein species and the highest microbial activity were also detected.Low Al^3+concentrations(<10 mg/L)could promote the removal efficiencies of COD and TN,yet excessive Al^3+levels(>10 mg/L)weakened microbial activity.Higher Al^3+concentrations(>30 mg/L)also inhibited the release of phosphorus in the anaerobic zone by reacting with PO4^3-.展开更多
Self-organized blastoids from extended pluripotent stem(EPs)cells possess enormous potential for investigating postimplantation embryo development and related diseases.However,the limited ability of postimplantation d...Self-organized blastoids from extended pluripotent stem(EPs)cells possess enormous potential for investigating postimplantation embryo development and related diseases.However,the limited ability of postimplantation development of Eps-blastoids hinders its further application.In this study,single-cell transcriptomic analysis indicated that the“trophectoderm(TE)-like structure”of EPSblastoids was primarily composed of primitive endoderm(PrE)-related cells instead of TE-related cells.We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure.Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation.Furthermore,we demonstrated that blastocyst-like structures reconstituted by combining the EPs-derived bilineage embryo-like structure(BLEs)with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses.In summary,our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.展开更多
基金primarily supported by the Ministry of Science and Technology of the People’s Republic of China(2017YFA0102602,2016YFA0100400)supported by the National Natural Science Foundation of China(81630035,31871448,31721003)+3 种基金the Shanghai Subject Chief Scientist Program(15XD1503500)Supporting Project of Medical Guidance(Western Medicine)of Science and Technology Commission of Shanghai Municipality(15411964600)Merck Serono China Research Fund for Fertility Experts,the Shanghai municipal medical and health discipline construction projects(2017ZZ02015)the Fundamental Research Funds for the Central Universities(1515219049)。
文摘Poor oocyte quality is associated with early embryo developmental arrest and infertility.Maternal gene plays crucial roles in the regulation of oocyte maturation,and its mutation is a common cause of female infertility.However,how to improve oocyte quality and develop effective therapy for maternal gene mutation remains elusive.Here,we use Zar1 as an example to assess the feasibility of genome transfer to cure maternal gene mutationecaused female infertility.We first discover that cytoplasmic deficiency primarily leads to Zar1-null embryo developmental arrest by disturbing maternal transcript degradation and minor zygotic genome activation(ZGA)during the maternal-zygotic transition.We next perform genome transfer at the oocyte(spindle transfer or polar body transfer)and zygote(early pronuclear transfer or late pronuclear transfer)stages to validate the feasibility of preventing Zar1 mutationecaused infertility.We finally demonstrate that genome transfer either at the oocyte or at the early pronuclear stage can support normal preimplantation embryo development and produce live offspring.Moreover,those pups grow to adulthood and show normal fertility.Therefore,our findings provide an effective basis of therapies for the treatment of female infertility caused by maternal gene mutation.
基金supported by the National Key R&DProject of China(2022YFC2702200 and 2021YFA1102900)the National Natural Science Foundation of China(32488101,32330030,82301921,32270909,82201881,92168205,31871448,31820103009,82022027,and 32300684)+9 种基金supported by the key project of the Science and Technology of Shanghai Municipality(19JC1415300 and 21JC1405500)the Natural Science Foundation of Shanghai(21ZR1450700)the ChinaPostdoctoral Science Foundation(2023M732660)the PostdoctoralFellowship Program of CPSF(GZB20230523)the Shanghai PilotProgram for Basic Research,the Shanghai Post-doctoral ExcellenceProgram(2022521,2022551,and 2023616)the China postdoctoral science foundation(2023M732660)the Postdoctoral Fellowship Program of CPSF(GZB20230523)the Fundamental Research Funds for the Central Universities(22120240435)the ShenzhenMedical Research Fund(B2402013)Peak Disciplines(TypeIV)of Institutions of Higher Learning in Shanghai.
文摘Assisted reproductive technology(ART)is associated with increased implantation failure and subsequent metabolic abnormalities in offspring,but the underlying mechanisms remain largely elusive.Here,we reveal that persistent Wnt signaling during the peri-implantation stage may be a key obstacle to the implantation of in vitro fertilization(IVF)embryos in a mouse model.Wnt activation affects the deposition of H3K27ac and H3K27me3 on pluripotency genes and bivalent genes,respectively,leading to the abnormal naïve-primed transition and suppressing expression of Otx2 in the epiblast.Furthermore,treatment with the Wnt inhibitor IWP2 promotes the redistribution of histone modifications and gene expression of epiblast.Importantly,Wnt inhibiting significantly improves implantation and intrauterine development of IVF embryos and subsequently ameliorates offspring metabolic abnormalities.Moreover,Wnt inhibiting markedly improves human peri-implantation embryo development and facilitates the transition from a naïve pluripotency state.Our study reveals a novel mechanism underlying the prevention of IVF embryo implantation failure and metabolic disorders in offspring.
基金This research was financially supported by the National Natural Science Foundation of China(Grant Nos.51678119 and 51808254)the Science and Technology Development Program of Jilin Province(Nos.20180201016SF and 20180101079JC)the Scientific Research Foundation from Education Department of Jilin Province(Nos.JJKH20180453KJ and JJKH20180454KJ).
文摘Aluminum ions produced by aluminum mining,electrolytic industry and aluminum-based coagulants can enter wastewater treatment plants and interact with activated sludge.They can subsequently contribute to the removal of suspended solids and affect activated sludge flocculation,as well as nitrogen and phosphorus removal.In this study,the effects of Al^3+on pollutant removal,sludge flocculation and the composition and structure of extracellular polymeric substances(EPS)were investigated under anaerobic,anoxic and oxic conditions.Results demonstrated that the highest chemical oxygen demand(COD)and total nitrogen(TN)removal efficiencies were detected for an Al^3+concentration of 10 mg/L.In addition,the maximal dehydrogenase activity and sludge flocculation were also observed at this level of Al^3+.The highest removal efficiency of total phosphorus(TP)was achieved at an Ar+concentration of30 mg/L.The flocculability of sludge in the anoxic zone was consistently higher than that in the anaerobic and oxic zones.The addition of Al^3+promoted the secretion of EPS.Tryptophan-like fluorescence peaks were detected in each EPS layer in the absence of Al^3+.At the Al^3+concentration of 10 mg/L,fulvic acid and tryptophan fluorescence peaks began to appear while the majority of protein species and the highest microbial activity were also detected.Low Al^3+concentrations(<10 mg/L)could promote the removal efficiencies of COD and TN,yet excessive Al^3+levels(>10 mg/L)weakened microbial activity.Higher Al^3+concentrations(>30 mg/L)also inhibited the release of phosphorus in the anaerobic zone by reacting with PO4^3-.
基金supported by the National Key R&D Program of China(Nos.2020YFA0112500 and 2021YFA1102900)the National Natural Science Foundation of China(Nos.31721003,81630035,82022027,31871448,32000418 and 31820103009)+2 种基金supported by the key project of the Science and Technology of Shanghai Municipality(Nos.19JC1415300 and 21JC1405500)the Shanghai municipal medical and health discipline construction projects(No.2017ZZ02015)the China Postdoctoral Science Foundation 2021M692437 and the Fundamental Research Funds for the Central Universities.
文摘Self-organized blastoids from extended pluripotent stem(EPs)cells possess enormous potential for investigating postimplantation embryo development and related diseases.However,the limited ability of postimplantation development of Eps-blastoids hinders its further application.In this study,single-cell transcriptomic analysis indicated that the“trophectoderm(TE)-like structure”of EPSblastoids was primarily composed of primitive endoderm(PrE)-related cells instead of TE-related cells.We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure.Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation.Furthermore,we demonstrated that blastocyst-like structures reconstituted by combining the EPs-derived bilineage embryo-like structure(BLEs)with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses.In summary,our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
