Exploring the impacts of senescence on implantation and early embryonic development using totipotent cell-derived blastoids
Introduction: Advanced maternal age is associated with reduced implantation and pregnancy rates, yet the underlying mechanisms remain poorly understood, and research models are limited. Objectives: Here, we aim to elucidate the impacts of senescence on implantation ability by employing blastoids to...
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2025-02-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123224000730 |
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| author | Yuxin Luo Chenrui An Ke Zhong Ping Zhou Dan Li Hui Liu Qing Guo Wei Wei Hen Pan Zheying Min Rong Li Yang Yu Yong Fan |
| author_facet | Yuxin Luo Chenrui An Ke Zhong Ping Zhou Dan Li Hui Liu Qing Guo Wei Wei Hen Pan Zheying Min Rong Li Yang Yu Yong Fan |
| author_sort | Yuxin Luo |
| collection | DOAJ |
| description | Introduction: Advanced maternal age is associated with reduced implantation and pregnancy rates, yet the underlying mechanisms remain poorly understood, and research models are limited. Objectives: Here, we aim to elucidate the impacts of senescence on implantation ability by employing blastoids to construct a novel research model. Methods: We used a novel three-dimensional system with totipotent blastomere-like cells (TBLCs) to construct TBL-blastoids and established senescence-related embryo models derived from oxidative stress-induced TBLCs. Results: Morphological and transcriptomic analyses revealed that TBL-blastoids exhibited characteristic blastocyst morphology, cell lineages, and a higher consistency in developmental rate. TBL-blastoids demonstrated the ability to develop into postimplantation structures in vitro and successfully implanted into mouse uteri, inducing decidualization and forming embryonic tissues. Importantly, senescence impaired the implantation potential of TBL-blastoids, effectively mimicking the impaired implantation ability and reduced pregnancy rates associated with advanced age. Furthermore, analysis of differentially expressed genes (DEGs) in human homologous deciduae revealed enrichment in multiple fertility-related diseases and other complications of pregnancy. The genes implicated in these diseases and the common DEGs identified in the lineage-like cells of the two types of TBL-blastoids and deciduae may represent potential targets for addressing impaired implantation potential. Conclusion: These results unveiled that TBL blastoids are an improved model for investigating implantation and early postimplantation, offering valuable insights into pregnancy-related disorders in women with advanced age and potential targets for therapeutic interventions. |
| format | Article |
| id | doaj-art-0ba394d34d924132a858fb6dfcc16f13 |
| institution | Kabale University |
| issn | 2090-1232 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj-art-0ba394d34d924132a858fb6dfcc16f132025-01-18T05:04:18ZengElsevierJournal of Advanced Research2090-12322025-02-0168115129Exploring the impacts of senescence on implantation and early embryonic development using totipotent cell-derived blastoidsYuxin Luo0Chenrui An1Ke Zhong2Ping Zhou3Dan Li4Hui Liu5Qing Guo6Wei Wei7Hen Pan8Zheying Min9Rong Li10Yang Yu11Yong Fan12State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing 100191, ChinaKey Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, ChinaKey Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, ChinaState Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing 100191, ChinaClinical Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, ChinaClinical Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, ChinaClinical Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, ChinaClinical Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, ChinaState Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing 100191, ChinaKey Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; Corresponding authors at: State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing 100191, China; Corresponding authors at: State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University Third Hospital, Beijing 100191, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing 100191, China; Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, China; Corresponding authors at: State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; Corresponding authors at: State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.Introduction: Advanced maternal age is associated with reduced implantation and pregnancy rates, yet the underlying mechanisms remain poorly understood, and research models are limited. Objectives: Here, we aim to elucidate the impacts of senescence on implantation ability by employing blastoids to construct a novel research model. Methods: We used a novel three-dimensional system with totipotent blastomere-like cells (TBLCs) to construct TBL-blastoids and established senescence-related embryo models derived from oxidative stress-induced TBLCs. Results: Morphological and transcriptomic analyses revealed that TBL-blastoids exhibited characteristic blastocyst morphology, cell lineages, and a higher consistency in developmental rate. TBL-blastoids demonstrated the ability to develop into postimplantation structures in vitro and successfully implanted into mouse uteri, inducing decidualization and forming embryonic tissues. Importantly, senescence impaired the implantation potential of TBL-blastoids, effectively mimicking the impaired implantation ability and reduced pregnancy rates associated with advanced age. Furthermore, analysis of differentially expressed genes (DEGs) in human homologous deciduae revealed enrichment in multiple fertility-related diseases and other complications of pregnancy. The genes implicated in these diseases and the common DEGs identified in the lineage-like cells of the two types of TBL-blastoids and deciduae may represent potential targets for addressing impaired implantation potential. Conclusion: These results unveiled that TBL blastoids are an improved model for investigating implantation and early postimplantation, offering valuable insights into pregnancy-related disorders in women with advanced age and potential targets for therapeutic interventions.http://www.sciencedirect.com/science/article/pii/S2090123224000730BlastocystsBlastoidsTotipotentImplantationSenescence |
| spellingShingle | Yuxin Luo Chenrui An Ke Zhong Ping Zhou Dan Li Hui Liu Qing Guo Wei Wei Hen Pan Zheying Min Rong Li Yang Yu Yong Fan Exploring the impacts of senescence on implantation and early embryonic development using totipotent cell-derived blastoids Journal of Advanced Research Blastocysts Blastoids Totipotent Implantation Senescence |
| title | Exploring the impacts of senescence on implantation and early embryonic development using totipotent cell-derived blastoids |
| title_full | Exploring the impacts of senescence on implantation and early embryonic development using totipotent cell-derived blastoids |
| title_fullStr | Exploring the impacts of senescence on implantation and early embryonic development using totipotent cell-derived blastoids |
| title_full_unstemmed | Exploring the impacts of senescence on implantation and early embryonic development using totipotent cell-derived blastoids |
| title_short | Exploring the impacts of senescence on implantation and early embryonic development using totipotent cell-derived blastoids |
| title_sort | exploring the impacts of senescence on implantation and early embryonic development using totipotent cell derived blastoids |
| topic | Blastocysts Blastoids Totipotent Implantation Senescence |
| url | http://www.sciencedirect.com/science/article/pii/S2090123224000730 |
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