Maternal DDB1 regulates apoptosis and lineage differentiation in porcine preimplantation embryos.

Autor: Ding, Biao, Gao, Di, Wang, Xuegu, Liu, Lei, Sun, Junpei, Liang, Meng, Wu, Fengrui, Liu, Yong, Zhang, Yunhai, Li, Xiang, Li, Wenyong
Předmět:
Zdroj: Reproduction, Fertility & Development; 2022, Vol. 34 Issue 12, p844-854, 11p
Abstrakt: 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. DDB1 is a gene that participates in meiotic resumption, ovulation, and embryonic stem cell maintenance. It is produced from maternal origin transcripts in early porcine embryos. DDB1 -deficiency enhanced cellular apoptosis in the blastocyst. Lack of DDB1 impaired trophectoderm formation and the pluripotency maintenance of blastocyst. DDB1 is a MEG, which plays a the crucial role of in porcine preimplantation embryonic development. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index