Non-genetic contributions of the sperm nucleus to embryonic development

Abstract

Recent data from several laboratories have provided evidence that the newly fertilized oocyte inherits epigenetic signals from the sperm chromatin that are required for proper embryonic development. For the purposes of this review, the term epigenetic is used to describe all types of molecular information that are transmitted from the sperm cell to the embryo. There are at least six different forms of epigenetic information that have already been established as being required for proper embryogenesis in mammals or for which there is evidence that it may do so. These are (i) DNA methylation; (ii) sperm-specific histones, (iii) other chromatin-associated proteins; (iv) the perinuclear theca proteins; (v) sperm-born RNAs and, the focus of this review; and (vi) the DNA loop domain organization by the sperm nuclear matrix. These epigenetic signals should be considered when designing protocols for the manipulation and cryopreservation of spermatozoa for assisted reproductive technology as necessary components for effective fertilization and subsequent embryo development.

Figure 1

Sperm-born epigenetic information. This diagram illustrates some of the molecular information that the sperm nucleus transmits to the oocytes, much of which may have direct influences on development. DNA methylation is the best-known example of non-DNA sequence information that is required for embryogenesis, but other potentially important elements have been described. Sperm DNA is tightly condensed by protamines into toroids (lower left inset), but some histones remain bound to the chromatin. The DNA is organized into loop domains that are required for DNA replication in the oocyte. Proteins of the nuclear matrix and perinuclear theca are also delivered to the oocyte. DTT, dithiothreitol; MARs, matrix attachment regions.