Maternal DDB1 regulates apoptosis and lineage differentiation in porcine preimplantation embryos
Biao Ding
A # , Di Gao B # , Xuegu Wang A , Lei Liu A , Junpei Sun A , Meng Liang C , Fengrui Wu D , Yong Liu D , Yunhai Zhang B , Xiang Li A * and Wenyong Li D *
+ Author Affiliations
- Author Affiliations
A Reproductive Medicine Center, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
B College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.
C School of Life Science, Bengbu Medical College, Bengbu 233030, China.
D Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation, Fuyang Normal University, Fuyang 236041, China.
* Correspondence to: xiangli@bbmc.edu.cn, liwenyong@fynu.edu.cn
# These authors contributed equally to this paper
Handling Editor: Ryan Cabot
Reproduction, Fertility and Development 34(12) 844-854 https://doi.org/10.1071/RD22028
Published online: 21 June 2022
© 2022 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)
Abstract
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.
Keywords: blastocyst, cellular apoptosis, DDB1, embryo, lineage differentiation, maternal-effect gene, porcine, preimplantation development.
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