Defective Histone H3K27 Trimethylation Modification in Embryos Derived from Heated Mouse Sperm

Abstract

The mouse sperm genome is resistant to in vitro heat treatment, and embryos derived from heated sperm can support full-term embryonic development, but the blastocyst rate and implantation rate are lower compared to embryos derived from fresh sperm. In the present study, the patterns of DNA methylation, histone H4K12 (ACH4K12) acetylation, H3K9 trimethylation (H3K9-TriM), and H3K27 trimethylation (H3K27-TriM) in preimplantation embryos derived from 65 °C-heated sperm were investigated. Although no evident changes in global DNA methylation, histone H4K12 (ACH4K12) acetylation, and H3K9 trimethylation (H3K9-TriM) were found, significantly lower levels of H3K27-TriM, which was thought to be one of the reasons for low efficiency of mouse cloning, were found in the inner cell mass of heated-sperm derived blastocysts. Thus, defective modification of H3K27-TriM might contribute to compromised development of embryos derived from heated sperm.

Mechanisms of histone H3 lysine 27 trimethylation remodeling during early mammalian development

“…A greater understanding of the epigenetic mechanisms controlling preimplantation development and early lineage differentiation is critical to comprehending the basis of early embryonic development and to devise methods and approaches to treat infertility. Defective reprogramming of H3K27me3 has been recently observed in mouse cloned embryos, 64 heated-sperm derived mouse embryos, 69 and bovine cloned embryos (Ross et al, unpublished). Further analysis of the potential consequence of alterations to the early H3K27me3 reprogramming is therefore warranted.…”

“…However, it was recently demonstrated that JMJD3 knockout (JMJD3-KO) mice can develop to term but are stillborn or die shortly after birth from respiratory failure. 69,70 Given that the JMJD3-KO mice would be expected to have the maternal JMJD3 gene contribution, since they are generated from a heterozygous female, we cannot make any conclusions regarding the necessity of maternal JMJD3 during murine preimplantation development. However, these results argue that embryonic JMJD3 is not necessary for early mouse development, given the ability of JMJD3-KO embryos to reach advanced developmental stages well beyond pre-implantation development.…”

Histone post‐translational modifications in preimplantation mouse embryos and their role in nuclear architecture

“…The same research group investigated epigenetic reprogramming in preimplantation embryos derived from 65°C‐heated sperm. Although they observed no evident changes for H4K12ac and H3K9me3, significantly lower levels of H3K27me3 were found in the ICM of heated‐sperm‐derived blastocysts (Chao et al, ).…”

Epigenetic dynamics during preimplantation development

“…For example in the mouse, H3K4me3 is significantly lower in the in vitro fertilized embryos compared with in vivo fertilized embryos (Wu et al 2012). Similarly lower levels of H3K27me3 are found in the inner cell mass of heated-sperm derived blastocysts when compared to untreated sperm derived blastocysts (Chao et al 2012), and cryopreservation can alter H4K12ac patterns in both oocytes and zygotes (Suo et al 2010). Despite these observations, it remains unclear if altered PTM levels persist in offspring or if surviving individuals contain appropriate epigenomic information – possibly correcting the epigenome during cell lineage differentiation at post-implantation stages.…”