Potential sperm contributions to the murine zygote predicted by in silico analysis

Abstract

Paternal contributions to the zygote are thought to extend beyond delivery of the genome and paternal RNAs have been linked to epigenetic transgenerational inheritance in different species. In addition, sperm-egg fusion activates several downstream processes that contribute to zygote formation, including PLC zeta-mediated egg activation and maternal RNA clearance. Since a third of the preimplantation developmental period in the mouse occurs prior to the first cleavage stage, there is ample time for paternal RNAs or their encoded proteins potentially to interact and participate in early zygotic activities. To investigate this possibility, a bespoke next-generation RNA sequencing pipeline was employed for the first time to characterise and compare transcripts obtained from isolated murine sperm, MII eggs and pre-cleavage stage zygotes. Gene network analysis was then employed to identify potential interactions between paternally and maternally derived factors during the murine egg-to-zygote transition involving RNA clearance, protein clearance and post-transcriptional regulation of gene expression. Our approach looked for factors in sperm, eggs and zygotes that could potentially interact co-operatively and synergistically during zygote formation. At least five sperm RNAs (, ,, and) met these requirements for a paternal contribution, which with complementary maternal co-factors suggest a wider potential for extra-genomic paternal involvement in the developing zygote.

RNA element discovery from germ cell to blastocyst

“…Relatively few paternal full-length RNAs are likely to be exclusively contributed to the embryo (22). Of note, the genes associated with the paternally transmitted REs did not overlap those long RNAs suggested to be paternally derived in mouse (101). This is likely due to the differences in genome activation, which occurs in the late 1- cell zygote in mouse (102), compared to the later 4–8 cell stage of human embryos, or other sperm derived RNAs providing a substitutive function (20,103).…”

Can trophectoderm RNA analysis predict human blastocyst competency?

“…Lack of synchronization between embryonic development on the one hand and receptivity of the female uterus on the other, as well as morphological and other anomalies of the uterus can also lead to implantation failure (Achache and Revel 2006;Margalioth et al 2006). Sperm quality is also linked to early embryo developmental defects (Loutradi et al 2006) with molecular paternal factors such as sperm DNA and RNA integrity thought to affect embryo implantation and pregnancy outcome (Robinson et al 2012;Sendler et al 2013;Ntostis et al 2017).…”

Sperm morphology and the evolution of intracellular sperm–egg interactions

“…As these techniques continue to be developed, greater understanding of the molecular contribution of sperm in early embryogenesis may expand, contributing to understanding the evolution of ISEIs. This is critical because eggs not only receive a structural sperm payload that needs to be dealt with, but also sperm RNAs that are essential for fertilization and zygotic development; such structural and/or signaling factors from the sperm may complement maternal factors that contribute to early programming of embryonic development (Miller, ; Ntostis et al., ). Here, we show a consistent and substantial change in ISEIs at a specific developmental stage across several species.…”