Function of sperm chromatin structural elements in fertilization and development

Abstract

Understanding how DNA is packaged in the mammalian sperm cell has important implications for human infertility as well as for the cell biology. Recent advances in the study of mammalian sperm chromatin structure and function have altered our perception of this highly condensed, inert chromatin. Sperm DNA is packaged very tightly to protect the DNA during the transit that occurs before fertilization. However, this condensation cannot sacrifice chromosomal elements that are essential for the embryo to access the correct sequences of the paternal genome for proper initiation of the embryonic developmental program. The primary levels of the sperm chromatin structure can be divided into three main categories: the large majority of DNA is packaged by protamines, a smaller amount (2-15%) retains histone-bound chromatin and the DNA is attached to the nuclear matrix at roughly 50 kb intervals. Current data suggest that the latter two structural elements are transferred to the paternal pronucleus after fertilization where they have important functional roles. The nuclear matrix organization is essential for DNA replication, and the histone-bound chromatin identifies genes that are important for embryonic development. These data support the emerging view of the sperm genome as providing, in addition to the paternal DNA sequence, a structural framework that includes molecular regulatory factors that are required for proper embryonic development.

Figure 1

Three major structural elements of sperm chromatin.

Figure 2

Inheritance of sperm chromatin structural elements by the embryo. DNA in round spermatids is packaged by histones (top) but during spermiogenesis, most of these are replaced by protamines (middle, red). After fertilization, the protamines are removed, and histones supplied by the oocyte replace them (bottom, light green). However, some histones that were retained in the spermatozoon (middle, dark green) are probably retained in the newly formed paternal pronucleus after fertilization. Sperm nuclear matrix attachment regions (MARs) are probably retained in the paternal pronucleus as well.