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Derivation of Mouse Trophoblast Stem Cells from Blastocysts
Published on: June 8, 2010
CircKDM5B sponges miR-128 to regulate porcine blastocyst development by modulating trophectoderm barrier function
Di Gao1,2, Xin Wang3, Ye-Lian Yan3
1Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong Shenzhen Hospital, Shenzhen, China.
Abstract:
Circular RNAs (circRNAs), which exert critical functions in the regulation of transcriptional and post-transcriptional gene expression, are found in mammalian cells but their functions in mammalian preimplantation embryo development remain poorly understood. Here, we showed that circKDM5B mediated miRNA-128 (miR-128) to regulate porcine early embryo development. We screened circRNAs potentially expressed in porcine embryos through an integrated analysis of sequencing data from mouse and human embryos, as well as porcine oocytes. An authentic circRNA originating from histone demethylase KDM5B (referred to as circKDM5B) was abundantly expressed in porcine embryos. Functional studies revealed that circKDM5B knockdown not only significantly reduced blastocyst formation but also decreased the number of total cells and trophectoderm (TE) cells. Moreover, the knockdown of circKDM5B resulted in the disturbance of tight junction assembly and impaired paracellular sealing within the TE epithelium. Mechanistically, miR-128 inhibitor injection could rescue the early development of circKDM5B knockdown embryos. Taken together, the findings revealed that circKDM5B functions as a miR-128 sponge, thereby facilitating early embryonic development in pigs through the modulation of gene expression linked to tight junction assembly.
Insights
Circular RNAs (circRNAs) regulate gene expression. In pigs, circKDM5B is crucial for early embryo development by sponging miR-128, impacting cell numbers and tight junction assembly.
Area of Science:
- * Developmental Biology
- * Molecular Biology
- * Genetics
Background:
- * Circular RNAs (circRNAs) are key regulators of gene expression in mammals.
- * Their specific roles in mammalian preimplantation embryo development are not well understood.
- * Understanding these roles is crucial for reproductive biology and developmental research.
Purpose of the Study:
- * To investigate the function of circRNAs in porcine early embryo development.
- * To identify specific circRNAs involved in regulating key developmental processes.
- * To elucidate the molecular mechanisms underlying circRNA-mediated regulation in embryos.
Main Methods:
- * Screening of circRNAs in porcine embryos using integrated sequencing data analysis.
- * Functional studies involving circRNA knockdown and microRNA inhibitor injection.
- * Assessment of blastocyst formation, cell counts, and tight junction integrity.
Main Results:
- * Identified circKDM5B, derived from histone demethylase KDM5B, as highly expressed in porcine embryos.
- * circKDM5B knockdown significantly impaired blastocyst formation, reduced cell numbers, and disrupted tight junction assembly.
- * circKDM5B acts as a sponge for miR-128, rescuing developmental defects upon inhibitor injection.
Conclusions:
- * circKDM5B plays a vital role in porcine early embryonic development.
- * It functions as a molecular sponge for miR-128, modulating gene expression.
- * This regulation is critical for cell proliferation and the establishment of epithelial integrity via tight junctions.
