The role of MAPK in male and female meiosis

The meiotic cell cyle differs from the mitotic cell cycle in several aspects. From the "cell cycle" point of view, the most striking difference, perhaps, is the lack of DNA duplication between the two meiotic divisions. In addition, the prophase of the first division is quite peculiar because it involves the annealing of homologous chromosomes and the exchange of genetic material between them. Possibly caused by the accuracy of these processes, in both the male and female gametes, the substeps of the first prophase are slow and the entire process requires several days to be completed [1, 2]. In addition, meiosis presents a marked sexual dimorphism [3]. In spermatocytes the cycle is continuous and, if DNA damage and/or spindle abnormalities do not occur, cells enter metaphase and divide into secondary spermatocytes without interruptions. In the mouse, male meiosis begins approximately 8-9 days after birth whereas the first divisions occur 16-18 days after birth; after its onset at puberty, male meiosis proceedes uninterrupted throughout the adult life of the organism [3]. On the other hand, in the female all oocytes enter meiosis in the embryonal gonad, at 13.5 days post-coitum (dpc), and they reach the diplotene stage of the first prophase before birth (17.5-18.5 dpc). Hence, they arrest in a stage named dictyate, when they partially decondense the chromatin, and accumulate maternal mRNAs and proteins that are required either for oocyte growth and maturation or for early embryogenesis after fertilization. Femal meiosis remains stalled until puberty, when under the influence of gonadotropins clusters of oocytes resume meiosis, complete the first division, enter the second division but they arrest again at the metaphase of the second cycle, awaiting for the spermatozoon to complete their meiotic cycle [3, 4]. Thus, several “checkpoints” that either delay or stop cell cycle progression must exist during the first prophase of the meiotic division in both spermatocytes and oocytes. On the other end, the delay and the arrest occur in the absence of obvious abnormalities in the cell, rendering the word “checkpoint” inadequate. For instance, in both dictyate oocytes and late pachytene spermatocytes, crossing over between homologous chromosomes is ultimated and the chiasmata have been formed [3, 5]; hence the arrest or the delay should not rely on unrepaired DNA. More likely, both the oocytes and the spermatocytes rely on the activation of a multistep program through either the synthesis of new components (both the dictyate oocyte and the pachytene spermatocyte are indeed actively transcribing cells) or the post-transcriptional or post-translational modification of mRNAs and proteins already stored in the cell. Interestingly, meiotic cells are particularly rich in RNA-binding proteins that have been reported to affect translational regulation of target mRNAs [6]. Moreover, once they have reached a competent stage, they can be rescued to proceed through the cycle if specific signal transduction pathways are turned on or off [3, 4]. In particular, it has been shown that oocytes from antral follicles can resume meiosis spontaneously, but the follicle environment maintains high levels of cAMP and cAMP-dependent kinase activity in the oocyte, which keeps the cell cycle halted [4]. Similarly, late pachytene spermatocytes arrest at this stage if isolated from the testicular environment, but they can be induced to complete the prophase and enter into metaphase by a brief treatment with a serine/threonine phosphatase inhibitor, which induces activation of several serine/threonine protein kinases involved in entry into M-phase both in mitosis and meiosis [7-9]. In both gametes, meiotic progression correlates with an almost simultaneus activation of MPF and of the MAPK pathway, but the specific roles of the two kinase pathways are not completely understood and their function in meiosis still require further investigation.