Low-level pyruvate inhibits early embryonic development and maternal mRNA clearance in mice

Abstract

Energy homeostasis and accomplishment of maternal-to-zygotic transition (MZT), which involves the timed processes of maternal mRNA clearance and zygotic genome activation (ZGA), are essential for mammalian embryogenesis. However, how energy substrates regulate maternal mRNA clearance and the underlying mechanisms have not yet been fully elucidated. Here, we found that mouse embryos were arrested at the 2-cell stage when the pyruvate level was reduced to one-fifth of the control level. Moreover, we observed that the mitochondrial contents and ROS levels were reduced. Interestingly, some maternal mRNA, including transcripts involved in the maternal factor-mediated mRNA decay (M-decay) pathway, was vastly degraded from 1-cell to 2-/4-cell embryos when cultured with control pyruvate levels, but the clearance of these transcripts was hindered when the pyruvate level was reduced. In contrast, some transcripts involved in the zygotic factor-mediated mRNA decay (Z-decay) pathway were vastly downregulated by the reduction in pyruvate. This effect was possibly due to a reduction in global transcription, as the embryos cultured with low-level pyruvate had lower transcription activity than embryos cultured with control pyruvate level. In summary, our findings demonstrate that low-level pyruvate inhibits maternal mRNA clearance, possibly by disrupting the M- and Z-decay pathways, extending our current understanding of the energy requirements of embryogenesis.

Keywords: Developmental arrest; Embryogenesis; Energy; Maternal mRNA clearance; Maternal-to-zygotic transition; Pyruvate.