Cyclin O Regulates Germinal Vesicle Breakdown in Mouse Oocytes1

Abstract

It is well accepted that oocyte meiotic resumption is mainly regulated by the maturation-promoting factor (MPF), which is composed of cyclin B1 (CCNB1) and cyclin-dependent kinase 1 (CDC2). Maturation-promoting factor activity is regulated by the expression level of CCNB1, phosphorylation of CDC2, and their germinal vesicle (GV) localization. In addition to CCNB1, cyclin O (CCNO) is highly expressed in oocytes, but its biological functions are still not clear. By employing short interfering RNA microinjection of GV-stage oocytes, we found that Ccno knockdown inhibited CDC2 (Tyr15) dephosphorylation and arrested oocytes at the GV stage. To rescue meiotic resumption, cell division cycle 25 B kinase (Cdc25b) and Ccnb1 were overexpressed in the Ccno knockdown oocytes. Unexpectedly, we found that Ccno knockdown did not affect CDC25B entry into the GV, and overexpression of CDC25B was not able to rescue resumption of oocyte meiosis. However, GV breakdown (GVBD) was significantly increased after overexpression of Ccnb1 in Ccno knockdown oocytes, indicating that GVBD block caused by cyclin O knockdown can be rescued by cyclin B1 overexpression. We thus conclude that cyclin O, as an upstream regulator of MPF, plays an important role in oocyte meiotic resumption in mouse oocytes.

Transcriptomic features of Pecten maximus oocyte quality and maturation

“…elegans , CKSs were demonstrated to have an essential role in meiosis M phase exit [ 92 ]; mice lacking CKS2, a mammalian homolog of yeast CKS1, were viable but sterile due to failure of female germ cells to progress past the first meiotic metaphase [ 93 ]. Likewise, CCNO is a cyclin acting as upstream regulator of MPF and demonstrated to play an important role in mouse oocytes since the CCNO knockdown blocked meiosis resumption [ 94 ]. Thus, higher expression of transcripts encoding CKS1 and CCNO in REL oocytes, might suggest that higher synthesis of cell-cycle regulators is necessary for scallop oocyte maturation.…”

Multiciliated Cells in Animals

“…Downstream from the MCIDAS/E2F complex also lies CCNO ( Fig. 1) (Stubbs et al 2012;Ma et al 2014;Wallmeier et al 2014), a cyclin-like protein first shown to be involved in oocyte meiosis resumption and apoptosis (Roig et al 2009;Ma et al 2013), and then shown to be expressed in MCC progenitors in the Xenopus skin and in the mouse brain, airways, and oviducts (Stubbs et al 2012;Funk et al 2015;Amirav et al 2016). Although its partners and molecular function remain to be determined, CCNO mutations or depletion lead to defects comparable to the C-MYB phenotype: defects in BB amplification, docking, and ciliogenesis Funk et al 2015).…”

Cyclins regulating oocyte meiotic cell cycle progression†

“…Cyclin B3 is a newly discovered cyclin that potentially forms active kinase complexes with CDK1; its knockdown and knockout arrested the oocytes at metaphase I [11–13]. Cyclin O (CCNO, also called UNG2 or UDG2) is a novel cyclin family protein expressed in oocytes whose knockdown inhibited CDK1 (Tyr15) dephosphorylation and arrested oocytes at the germinal vesicle (GV) stage [14]; however, Ccno -deficient male and female mice are partly fertile [15]. In this review, we will summarize and discuss the functions of various cyclins mentioned above in line with time course of meiotic maturation.…”

“…Cyclin O is highly expressed in oocytes and localizes in the nucleus of GV-stage oocytes. We found that cyclin O was essential for oocyte meiotic resumption because Ccno knockdown inhibited CDK1 (Tyr15) dephosphorylation, which was required for MPF activation [14]. Ccno knockout mice have been generated, and 57% mutant mice developed a prominent hydrocephalus, leading to abnormal head morphology and growth retardation; remaining male and female mice that were not severely affected by hydrocephalus were fertile at maturity age [15].…”