Journal
REPRODUCTION FERTILITY AND DEVELOPMENT
Volume 34, Issue 12, Pages 844-854Publisher
CSIRO PUBLISHING
DOI: 10.1071/RD22028
Keywords
blastocyst; cellular apoptosis; DDB1; embryo; lineage differentiation; maternal-effect gene; porcine; preimplantation development
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Funding
- University Natural Science Research Project of Anhui Province [KJ2019A0517]
- First Affiliated Hospital of Bengbu Medical College Science Fund for Outstanding Young Scholars [2019byyfyyq10]
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DDB1 is found to be a maternal-effect gene in porcine preimplantation embryos, and its deficiency leads to significant changes in gene expression and development, indicating its crucial role in lineage differentiation and pluripotency maintenance.
Context: Maternal-effect genes (MEGs) play a critical role in modulating both cellular and molecular biology events in preimplantation embryonic development. Damage-specific DNA binding protein 1 (DDB1) is a gene that participates in meiotic resumption, ovulation, and embryonic stem cell maintenance. Its function in preimplantation development is not well-studied. Aims: We aimed to explore the expression pattern, genomic heritage, and potential molecular mechanisms of DDB1 in preimplantation embryos in porcine. Methods: In this study, RNA interference, microinjection, RT-qPCR, immunofluorescence staining and single-cell RNA sequencing were used to explore the molecular function of DDB1 in porcine preimplantation embryos. Key results: DDB1 was found to be expressed in germinal vesicle (GV) and Meiosis II (MII) oocytes and in preimplantation embryos. We confirmed it is a MEG. DDB1-deficient blastocysts had a significantly reduced number of trophectoderm cells, an increased apoptotic cell number and increased apoptosis index. According to a next-generation sequencing (NGS) analysis, 236 genes (131 upregulated and 105 downregulated) significantly changed in the DDB1-deficient morula. The myeloid leukaemia factor 1 (MLF1) and yes-associated protein 1 (YAP1) expressions were significantly upregulated and downregulated respectively, in the DDB1-deficient morula. In combination with the decreased expression of TEAD4, CDX2, GATA3, OCT4, and NANOG and the increased expression of SOX2 in the blastocyst, DDB1 may play a role in determining lineage differentiation and pluripotency maintenance. Conclusions: DDB1 is a MEG and it plays a crucial role in porcine preimplantation embryonic development. Implications: This study provides a theoretical basis for further understanding the molecular mechanisms of preimplantation embryo development.
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