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

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.

Highlights

• Serendipitious discovery of disruptive evolution of haploid asexual reproductive mode and preimplantation embryogenetic fitness in FVB strain of mice.

• Novel self-correcting totipotency clock regulates blastulation potential in mammals including humans and limits haploid asexual embryogenesis

• Evolution 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.

Graphical Summary