Oocyte-stored Mif promotes preimplantation development as an embryonic extracellular signal
- 1State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
Abstract
Mammalian preimplantation embryos develop more efficiently in groups than in isolation, suggesting that embryos secrete embryotrophic factors that promote development. However, the endogenous embryotrophic signals responsible for this long-recognized phenomenon remain incompletely defined. Using an unbiased proteomic screen for stable maternal proteins that may function as embryonic extracellular signals, we identified the cytokine macrophage migration inhibitory factor (Mif) as an abundant oocyte-stored protein that persists for several days after fertilization in mice. Quantitative measurements of spent culture medium reveal that developing embryos release Mif, with a substantial fraction derived from the maternal deposit. Extracellular Mif levels peak 3-4 days post fertilization, the same period when Mif knockout preimplantation embryos produce its strongest phenotype. Embryos lacking maternal, but not zygotic, Mif display defective blastocyst growth even in group culture. Individually cultured embryos exhibit similar blastocyst growth defects that can be rescued by supplementing recombinant Mif at physiologically relevant concentrations. Mif activates the PI3K-Akt-mTORC1 pathway through the cell-surface receptor Cd74 to promote blastocyst growth and cell proliferation. Together, these findings identify Mif as a potential endogenous contributor to the density-dependent embryotrophic effects and reveal that maternally stored proteins may function long after fertilization as extracellular signaling molecules to support preimplantation development in mammals.
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BibTeX
@misc{li2026oocytestored,
title = {{Oocyte-stored Mif promotes preimplantation development as an embryonic extracellular signal}},
author = {J. X. H. Li and H. Wang and L. Li and T. Aziz and H. Huang and C. Li and G. Li and H. Li and J. Li and L. Tian and Z. Wei and T. Zhang and T. Zhu and Y. Chen and H. Deng and X. Wu and A. Meng},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.03.763862},
url = {https://www.biorxiv.org/content/10.64898/2026.11.03.763862v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Oocyte-stored Mif promotes preimplantation development as an embryonic extracellular signal
AU - J. X. H. Li
AU - H. Wang
AU - L. Li
AU - T. Aziz
AU - H. Huang
AU - C. Li
AU - G. Li
AU - H. Li
AU - J. Li
AU - L. Tian
AU - Z. Wei
AU - T. Zhang
AU - T. Zhu
AU - Y. Chen
AU - H. Deng
AU - X. Wu
AU - A. Meng
PY - 2026
DA - 2026/11/03
PB - bioRxiv
DO - 10.64898/2026.11.03.763862
UR - https://www.biorxiv.org/content/10.64898/2026.11.03.763862v1
AB - Mammalian preimplantation embryos develop more efficiently in groups than in isolation, suggesting that embryos secrete embryotrophic factors that promote development. However, the endogenous embryotrophic signals responsible for this long-recognized phenomenon remain incompletely defined. Using an unbiased proteomic screen for stable maternal proteins that may function as embryonic extracellular signals, we identified the cytokine macrophage migration inhibitory factor (Mif) as an abundant oocyte-stored protein that persists for several days after fertilization in mice. Quantitative measurements of spent culture medium reveal that developing embryos release Mif, with a substantial fraction derived from the maternal deposit. Extracellular Mif levels peak 3-4 days post fertilization, the same period when Mif knockout preimplantation embryos produce its strongest phenotype. Embryos lacking maternal, but not zygotic, Mif display defective blastocyst growth even in group culture. Individually cultured embryos exhibit similar blastocyst growth defects that can be rescued by supplementing recombinant Mif at physiologically relevant concentrations. Mif activates the PI3K-Akt-mTORC1 pathway through the cell-surface receptor Cd74 to promote blastocyst growth and cell proliferation. Together, these findings identify Mif as a potential endogenous contributor to the density-dependent embryotrophic effects and reveal that maternally stored proteins may function long after fertilization as extracellular signaling molecules to support preimplantation development in mammals.
ER -