OVOL1/2 regulate trophectoderm differentiation during the morula-to-blastocyst transition
Abstract
The blastocyst formation rate of human embryos cultured in vitro for assisted reproduction is approximately 50%, with most embryos arresting at the cleavage stage; however, the underlying mechanisms remain poorly understood. Here, we performed single-cell RNA sequencing of biopsied blastomeres from morphologically high-quality 8-cell embryos and tracked the developmental progression of the remaining embryos to the blastocyst stage. Embryos that failed to form blastocysts exhibited impaired zygotic genome activation (ZGA). We identified OVOL1/2 as critical ZGA genes that were markedly underactivated in these embryos. Functional analyses in both mouse and human embryos demonstrate that depletion of OVOL1/2 disrupts trophectoderm differentiation via ARPC1B-dependent mechanisms, thereby impairing the morula-to-blastocyst transition. Collectively, these findings provide mechanistic insights into preimplantation embryonic development and reveal potential causes of blastocyst formation failure.
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BibTeX
@article{zhu2026ovol12,
title = {{OVOL1/2 regulate trophectoderm differentiation during the morula-to-blastocyst transition}},
author = {Yi Zhu and Xueqin Chen and Xin Deng and Shuoping Zhang and Jue Zhang and Fei Meng and Qinwei Zhou and Yifan Gu and Fei Gong and Guangxiu Lu and Ge Lin and Lizhi Leng},
journal = {Communications Biology},
year = {2026},
month = oct,
doi = {10.1038/s42003-026-11168-x},
url = {https://www.nature.com/articles/s42003-026-11168-x},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - OVOL1/2 regulate trophectoderm differentiation during the morula-to-blastocyst transition
AU - Yi Zhu
AU - Xueqin Chen
AU - Xin Deng
AU - Shuoping Zhang
AU - Jue Zhang
AU - Fei Meng
AU - Qinwei Zhou
AU - Yifan Gu
AU - Fei Gong
AU - Guangxiu Lu
AU - Ge Lin
AU - Lizhi Leng
PY - 2026
DA - 2026/10/29
JO - Communications Biology
DO - 10.1038/s42003-026-11168-x
UR - https://www.nature.com/articles/s42003-026-11168-x
AB - The blastocyst formation rate of human embryos cultured in vitro for assisted reproduction is approximately 50%, with most embryos arresting at the cleavage stage; however, the underlying mechanisms remain poorly understood. Here, we performed single-cell RNA sequencing of biopsied blastomeres from morphologically high-quality 8-cell embryos and tracked the developmental progression of the remaining embryos to the blastocyst stage. Embryos that failed to form blastocysts exhibited impaired zygotic genome activation (ZGA). We identified OVOL1/2 as critical ZGA genes that were markedly underactivated in these embryos. Functional analyses in both mouse and human embryos demonstrate that depletion of OVOL1/2 disrupts trophectoderm differentiation via ARPC1B-dependent mechanisms, thereby impairing the morula-to-blastocyst transition. Collectively, these findings provide mechanistic insights into preimplantation embryonic development and reveal potential causes of blastocyst formation failure.
SN - 2399-3642
ER -