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bioRxiv · 10.1101/2024.08.19.608531

Haploid Asexual Blastocyst Fitness Varies Across Mouse Strains Related to Efficiency of Exit From Totipotency

Crasta, D. N.·Lee, S. W.·Fredrickson, J.·Thejo, T.·Adiga, S. K.·Zhao, Y.·Kalthur, G.·Kannan, N.
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Abstract

In vitro activation, both sexually and asexually, facilitates assessing the reproductive mode and fitness of mammalian oocytes. Herein, we present evidence of the enhancement of asexual haploid blastocyst fitness in one selectively-inbred Mus musculus population. We tracked sexually and asexually activated-oocytes as they exited totipotency and self-organized into blastocyst-stage embryos. We examined haploid and diploid parthenogenetic potential of activated-oocytes. Unexpectedly, [~]90% of selectively-inbred mouse oocytes that were asexually activated successfully generated haploid blastocysts, contrasting with [~]90% failure in randomly-outbred mice. Furthermore, by closely tracking the timeline of exit from totipotency, we propose a novel self-correcting totipotency clock, crucial for timely exit from totipotency and successful embryogenesis across mammals. Insufficiency in this self-correcting prerequisite, will alter the fitness landscape in different reproductive modes. Collectively, this work provides a quantitative framework to investigate the unknown disruptive evolutionary trajectories of reproductive modes and fitness of females in anisogamous species. HighlightsO_LISerendipitious discovery of disruptive evolution of haploid asexual reproductive mode and preimplantation embryogenetic fitness in FVB strain of mice. C_LIO_LINovel self-correcting totipotency clock regulates blastulation potential in mammals including humans and limits haploid asexual embryogenesis C_LIO_LIEvolution of haploid asexual reproductive mode and preimplantation embryogenetic fitness in FVB mouse is linked to a superior self-correcting totipotency clock lacking in other animals. C_LI Graphical Summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/608531v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@12b9f77org.highwire.dtl.DTLVardef@f2759forg.highwire.dtl.DTLVardef@84029org.highwire.dtl.DTLVardef@1ac7f42_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Crasta, D. N., Lee, S. W., Fredrickson, J., Thejo, T., Adiga, S. K., Zhao, Y., Kalthur, G., Kannan, N.. 2024-08-19. Haploid Asexual Blastocyst Fitness Varies Across Mouse Strains Related to Efficiency of Exit From Totipotency. https://doi.org/10.1101/2024.08.19.608531

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