Normal embryo development needs MEIG1-mediated sperm formation

Abstract

Normal embryo development is a complex process that requires normal sperm to fertilize normal oocytes. Abnormal embryogenesis can be caused by either abnormal oocytes or abnormal sperm. However, the impact of sperm-associated factors is often underappreciated. Association between defects in sperm chromatin and poor embryo development has been consistently reported. In sperm cells, most histones are replaced by protamines to remodel sperm cell chromatin. However, the mechanism of nuclear protein replacement is largely unknown. Meiosis expressed gene 1 (MEIG1) plays a unique role in male fertility. The protein is recruited to the manchette at a late stage of spermatogenesis. The manchette is a unique structure only present in male germ cells, and one of the proposed functions is replacing histones with protamines. In this study, ICSI was conducted using sperm heads from the Meig1 KO mice. Significantly reduced fertilization was observed, and few embryos developed to blastocysts, which were associated with severe sperm DNA damage. Thus, we discovered an unexpected role for MEIG1 extending beyond spermatogenesis to include a role in embryogenesis, likely through remodeling sperm chromatin.