Molecular and Cellular Endocrinology 187 (2002) 161 – 171 Translational and post-translational modifications in meiosis of the mammalian oocyte Liat Ben-Yehoshua Josefsberg, Nava Dekel * Department of Biological Regulation, Weizmann Institute of Science, 76100 Rehoot, Israel Abstract The fully-grown oocyte is transcriptionally inactive. Therefore, translational and post-translational modifications furnish the control mechanism of key components governing meiosis. Regulation by protein synthesis provides an irreversible unidirectional mechanism for an extended period that can be restricted by a complementary degradation of the same protein. Both processes utilize tight measures to ensure precise expression at the right time in the right place. Rapid modifications such as phosphorylation and dephosphorylation supply reversible means to regulate protein action. Information regarding these extremely exciting issues is being accumulated recently in an exponential rate. However, the vast majority of these data is generated from studies conducted on Xenopus oocytes. We fully agree with Andrew Murray’s statement that ‘‘The modern trend of promoting research on a small number of ‘model’ organisms will eventually deprive us of the opportunity to study interesting biology’’ [Cell 92 (1992) 157]. Thus, despite all of the enormous technical difficulties resulting from the limited availability of biological material we extended our interest to mammalian model systems. Our review will attend to certain examples of such modifications in the regulatory pathway of meiosis in mammalian oocytes. © 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Oocyte; Meiosis; MPF; MAPK; Mos; Proteasome www.elsevier.com/locate/mce 1. Cyclic AMP is the meiotic arrestor Fertilization is the central event in reproduction. However, this interaction between the oocyte and the sperm will not take place in gametes that have not resumed meiosis. Meiosis in the mammalian oocyte is initiated during embryonic life, proceeds up to the diplotene stage of the first prophase and is arrested around birth. Meiotic arrest persists throughout infancy until the onset of puberty. In the sexually mature female at each cycle, one or more oocytes, according to the species, respond to the hormonal stimulus and reinitiate their meiotic division. This hormonal stimulus is pro- vided by the mid-cycle surge of the pituitary leutenizing hormone (LH) that induces both resumption of meiosis and ovulation. However, reinitiation of meiosis in mam- mals can also occur spontaneously, upon removal of the oocyte from the ovarian follicle (reviewed by Dekel, 1995). The observation, that meiotically arrested oocytes, removed from the ovary spontaneously resume meiosis, was initially reported in 1935 and raised the idea that the ovarian follicle provides the oocyte with an in- hibitory agent responsible for its meiotic arrest (Pincus and Enzmann, 1935). The first clue regarding the possi- ble identity of this inhibitory agent was provided by another study published almost 40 years later (Cho et al., 1974). This study demonstrated that the sponta- neous reinitiation of meiosis could be blocked by eleva- tion of intraoocyte concentrations of cAMP. Additionally, phosphodiesterase inhibitors, that do not elevate cAMP concentrations but rather maintain the nucleotide at amounts present in the oocyte just prior to its separation from the ovarian follicle, were equally effective in preventing maturation (Cho et al., 1974, Lindner et al., 1974). Taking these last observations into account we suggested that cAMP provided to the oocyte by the follicular cells could possibly serve as the ‘meiotic arrestor’. The inhibitory effect of cAMP has been thor- oughly characterized by us in rat oocytes (Dekel and Beers, 1978, 1980) and confirmed by other laboratories in other animal species. It has been later demonstrated * Corresponding author. Tel.: +972-8-934-3716; fax: +972-8-934- 4116. E-mail address: nava.dekel@weizmann.ac.il (N. Dekel). 0303-7207/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved. PII:S0303-7207(01)00688-8