Oocyte-specific genes regulate follicle formation, fertility and early mouse development

Abstract

Gene products expressed in oocytes play important roles in folliculogenesis, fertilization and pre-implantation development. Factor in the Germline, alpha (FIGalpha) is a basic helix-loop-helix (bHLH) transcription factor first detected in oocytes at E13.5 that persists in adults. Female mice lacking FIGalpha are unable to form primordial follicles which results in massive depletion of oocytes and sterility. FIGalpha is also required for expression of the zona pellucida genes that encode ZP1, ZP2, and ZP3. Mice lacking ZP1 form structurally abnormal zonae and have decreased fecundity. Mice lacking ZP3 have no zona matrix despite the presence of the other two zona proteins. Although, folliculogenesis occurs in Zp3 null mice, few eggs are ovulated and females are sterile. Transgenic mice expressing human ZP3 have been crossed with Zp3 null mice and reconstitute a chimeric zona pellucida matrix (moZP1, moZP2, huZP3). Unexpectedly, human sperm do not bind to 'humanized' zonae pellucidae in vitro, but mouse sperm do. Although, late in oogenesis, oocytes becomes transcriptionally inactive and maternal RNA is degraded, the activation of early development requires pre-existing maternal products from the egg. Maternal antigen that embryos require (Mater) is a single-copy gene that is transcribed in growing oocytes and, although its transcripts are degraded during meiotic maturation, MATER protein persists into the blastocyst. Female mice lacking this 125 kDa cytoplasmic protein produce no off-spring because of an embryonic block at the early cleavage stage. Thus, Mater represents one of the few documented maternal effect genes in mammalian development.