Posttranscriptional Regulation of Cyclin A1 and Cyclin A2 During Mouse Oocyte Meiotic Maturation and Preimplantation Development1

Abstract

A shift from a meiotic cell cycle to a mitotic cell cycle occurs following fertilization. The molecular basis for this transition, however, is poorly understood. Although cyclin A1 is proposed to regulate M phase in the meiotic cell cycle, and cyclin A2 is proposed to regulate S and M phases in the mitotic cell cycle, little is known about changes in the expression levels of cyclin A1 and A2 during meiotic and mitotic cell cycles in mammalian oocytes. We report that the mRNA levels of both cyclins A1 and A2 decrease during oocyte maturation. The amount of cyclin A1 mRNA then increases between the one-cell and blastocyst stages, whereas that of cyclin A2 remains relatively constant. The amount of cyclin A1 protein declines during maturation and is not readily detected from the two-cell to the blastocyst stage. In contrast, cyclin A2 is not readily detected in the oocyte and metaphase II-arrested egg but is detected following fertilization and throughout the subsequent stages of preimplantation development. The appearance of cyclin A2 protein following fertilization positively correlates with an increase in the size of the mRNA. This increase, as well as the increase in the amount of cyclin A2 protein, is prevented by 3'-deoxyadenosine (3'-dA), an inhibitor of polyadenylation. Consistent with a role for cyclin A2 in regulating the G1/S transition, 3'-dA also inhibits DNA replication in treated one-cell embryos. These results suggest that regulation of expression of cyclins A1 and A2 is under posttranscriptional regulation and that the observed changes in their expression may be involved in the transformation of a meiotic cell cycle to a mitotic cell cycle following fertilization.

The γ isoform of CaM kinase II controls mouse egg activation by regulating cell cycle resumption

“…Microarray analysis of polysomal mRNAs in metaphase II eggs and late zygotes demonstrates that thousands of transcripts are differentially translated in the zygote as compared to the unfertilized egg (39). Nevertheless, only a few maternal transcripts that are mobilized during egg activation have been identified, including spindlin (22), and cyclin A2 (40). Whereas the presence of a cytoplasmic polyadenylation element (CPE) in the 3′UTR of mRNAs is widely recognized as a determinant for translation during meiotic maturation (41), the sequence responsible for marking transcripts for recruitment after fertilization is poorly defined.…”

Zygotic control of maternal cyclin A1 translation and mRNA stability

“…Replacement of the maternal cyclin A by the somatic cyclin A has been observed in the early development of both frogs and mice (Howe et al, 1995;Fuchimoto et al, 2001). The functional significance of this replacement is unclear.…”

“…The functional significance of this replacement is unclear. It has been hypothesized to be involved in either the meiotic to mitotic transition (Fuchimoto et al, 2001), or in a switch from maternal to zygotic control of cell cycle progression (Howe et al, 1995). In Xenopus, before the MBT, the embryonic cell cycle is composed of a succession of S and M phases, enabling the cells to divide synchronously every 25-30 min.…”

Not all germ cells are created equal: Aspects of sexual dimorphism in mammalian meiosis

“…Cyclin A1 (encoded by Ccna1) is a germ cell specific cyclin thought to activate meiotic metaphase transition during meiosis I, in conjunction with MPF (Sweeney et al 1996, Fuchimoto et al 2001, Salazar et al 2003, Wolgemuth et al 2004. Ccna1 -/-male mice are infertile due to Figure 3 Cell cycle events in mouse gametogenesis.…”