Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.Howeve...Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.However,a systematic characterization of its reproductive toxicity is still missing.This study aims to explore the male reproductive toxicity caused by GenX exposure and the potential cellular and molecular regulatory mechanisms behind it.Results Normally developing mice were exposed to GenX,and testicular tissue was subsequently analyzed and validated using single-cell RNA sequencing.Our results revealed that GenX induced severe testicular damage,disrupted the balance between undifferentiated and differentiated spermatogonial stem cells,and led to strong variation in the cellular dynamics of spermatogenesis.Furthermore,GenX exposure caused global upregulation of testicular somatic cellular inflammatory responses,increased abnormal macrophage differentiation,and attenuated fibroblast adhesion,disorganizing the somatic-germline interactions.Conclusions In conclusion,this study revealed complex cellular dynamics and transcriptome changes in mouse testis after GenX exposure,providing a valuable resource for understanding its reproductive toxicity.展开更多
Dynamic crosstalk between the embryo and mother is crucial during implantation.Here,we comprehensively profile the single-cell transcriptome of pig peri-implantation embryos and corresponding maternal endometrium,iden...Dynamic crosstalk between the embryo and mother is crucial during implantation.Here,we comprehensively profile the single-cell transcriptome of pig peri-implantation embryos and corresponding maternal endometrium,identifying 4 different lineages in embryos and 13 cell types in the endometrium.Cell-specific gene expression characterizes 4 distinct trophectoderm subpopulations,showing development from undifferentiated trophectoderm to polar and mural trophectoderm.Dynamic expression of genes in different types of endometrial cells illustrates their molecular response to embryos during implantation.Then,we developed a novel tool,ExtraCellTalk,generating an overall dynamic map of maternal-foetal crosstalk using uterine luminal proteins as bridges.Through cross-species comparisons,we identified a conserved RBP4/STRA6 pathway in which embryonic-derived RBP4 could target the STRA6 receptor on stromal cells to regulate the interaction with other endometrial cells.These results provide insight into the maternal-foetal crosstalk during embryo implantation and represent a valuable resource for further studies to improve embryo implantation.展开更多
基金supported by the Guangdong Provincial Key Area Research and Development Program[grant number 2022B0202090002]China Postdoctoral Science Foundation[grant number 2024M760977].
文摘Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.However,a systematic characterization of its reproductive toxicity is still missing.This study aims to explore the male reproductive toxicity caused by GenX exposure and the potential cellular and molecular regulatory mechanisms behind it.Results Normally developing mice were exposed to GenX,and testicular tissue was subsequently analyzed and validated using single-cell RNA sequencing.Our results revealed that GenX induced severe testicular damage,disrupted the balance between undifferentiated and differentiated spermatogonial stem cells,and led to strong variation in the cellular dynamics of spermatogenesis.Furthermore,GenX exposure caused global upregulation of testicular somatic cellular inflammatory responses,increased abnormal macrophage differentiation,and attenuated fibroblast adhesion,disorganizing the somatic-germline interactions.Conclusions In conclusion,this study revealed complex cellular dynamics and transcriptome changes in mouse testis after GenX exposure,providing a valuable resource for understanding its reproductive toxicity.
基金supported by the National Key Research and Development Program of China(2021YFD1301103)the National Natural Science Foundation of China(31802033)+2 种基金the Guangdong Provincial Key Area Research and Development Program(2022B0202090002)the Guangdong Basic and Applied Basic Research Foundation(2022A1515011131,2023A1515030193)the Guangdong Provincial Promotion Project on Preservation and Utilization of Local Breed of Livestock and Poultry(2018143).
文摘Dynamic crosstalk between the embryo and mother is crucial during implantation.Here,we comprehensively profile the single-cell transcriptome of pig peri-implantation embryos and corresponding maternal endometrium,identifying 4 different lineages in embryos and 13 cell types in the endometrium.Cell-specific gene expression characterizes 4 distinct trophectoderm subpopulations,showing development from undifferentiated trophectoderm to polar and mural trophectoderm.Dynamic expression of genes in different types of endometrial cells illustrates their molecular response to embryos during implantation.Then,we developed a novel tool,ExtraCellTalk,generating an overall dynamic map of maternal-foetal crosstalk using uterine luminal proteins as bridges.Through cross-species comparisons,we identified a conserved RBP4/STRA6 pathway in which embryonic-derived RBP4 could target the STRA6 receptor on stromal cells to regulate the interaction with other endometrial cells.These results provide insight into the maternal-foetal crosstalk during embryo implantation and represent a valuable resource for further studies to improve embryo implantation.
