The Mos/mitogen-activated protein kinase (MAPK) pathway regulates the size and degradation of the first polar body in maturing mouse oocytes.

Abstract

Mos is an upstream activator of mitogenactivated protein kinase (MAPK) and, in mouse oocytes, is responsible for metaphase II arrest. This activity has been likened to its function in Xenopus oocytes as a component of cytostatic factor. Thus, Mos-deficient female mice are less fertile and oocytes derived from these animals fail to arrest at metaphase II Here we show that maturing MOS-'-oocytes fail to activate MAPK throughout meiosis, while p34edc2 kinase activity is normal until late in metaphase II when it decreases prematurely. Phenotypically, the first meiotic division of MOS-/-oocytes frequently resembles mitotic cleavage or produces an abnormally large polar body. In these oocytes, the spindle shape is altered and the spindle fails to translocate to the cortex, leading to the establishment of an altered cleavage plane. Moreover, the first polar body persists instead of degrading and sometimes undergoes an additional cleavage, thereby providing conditions for parthenogenesis. These studies identify meiotic spindle formation and programmed degradation of the first polar body as new and important roles for the Mos/MAPK pathway.The mos protooncogene encodes a protein serine/threonine kinase (1) and Mos is expressed at high levels in oocytes undergoing meiotic maturation (2,3). InXenopus oocytes, Mos has been shown to function as a meiotic initiator (4, 5) and an active component of cytostatic factor (CSF) (6), an activity that is responsible for the arrest of an unfertilized egg at metaphase II of meiosis (7). More recently, mitogen-activated protein kinase (MAPK), which is highly activated throughout oocyte maturation (8-12), has been identified as one of the major downstream targets of Mos (13)(14)(15)(16)(17). Mos has been implicated in the activation and stabilization of p34cdc2 kinase as maturation promoting factor (MPF) (4,(18)(19)(20), and evidence for the mutual dependency between MPF and the Mos/MAPK pathway in Xenopus oocytes has been reported (8,21,22).More recently, it has been shown that oocytes from mice homozygously deficient in mos (MOS-/-) fail to arrest at metaphase II and undergo parthenogenetic activation (23,24). These observations clearly demonstrated that Mos is an active component of CSF, but left unclear whether Mos functions prior to metaphase II arrest as it does in Xenopus.We generated MOS-'-mice and confirmed previous reports (23,24) that oocytes from these animals fail to arrest at metaphase II and instead undergo parthenogenetic activation.Also we show that maturing oocytes from MOS-1-mice fail to activate MAPK, while p34cdc2 kinase activation is normal until metaphase, when it decreases prematurely. Moreover, in MOS-'-oocytes, we observe that the first polar bodies can be abnormally large and sometimes undergo an additional cleavage instead of undergoing rapid degeneration. Thus, in addition to CSF activity, Mos/MAPK are required for regulating the size and degradation of the first polar body. MATERIALS AND METHODSGeneration of MOS-1-Knockout Mice. A replacement-type ...

A morpholino phenocopy of the mouse MOS mutation

“…2g). These results are similar to previous reports (Choi et al, 1996;Svoboda et al, 2000). Germinal vesicle stage oocytes were included in this experiment as a negative control (Fig.…”

“…In mos-deficient mice or in mouse oocytes injected with mos double-stranded RNA, approximately 60 -75% of oocytes fail to arrest at metaphase II and undergo parthenogenetic activation (Choi et al, 1996;Colledge et al, 1994;Hashimoto et al, 1994;Wianny and Zernicka-Goetz, 2000). In this study, microinjection of 340 pg of mos MO, 17 pg of mos MO, or 340 pg of control MO into the cytoplasm of germinal vesicle stage mouse oocytes resulted in respective parthenogenetic activation rates of 56, 23, and 0% when scored 20 h after 3-isobutyl-1-methyl-xanthine (IBMX) removal (Fig.…”

Does first polar body morphology predict oocyte performance during ICSI treatment?

“…The first related to the natural apoptotic process of the first polar body and the second associated with the chromosomal integrity of the oocyte. It is well recognized today that after the extrusion of the 1 PB, a programmed cell death of this structure follows by apoptosis [16], leading eventually to its disintegration. This process is usually completed by approximately 20 h following 1 PB extrusion [17].…”

Effects of MEK inhibitor U0126 on meiotic progression in mouse oocytes: microtuble organization, asymmetric division and metaphase II arrest

“…But the first meiotic division is symmetric in some mos -/-oocytes [8]. In wild-type oocytes the spindle formed in the center of oocytes and migrated to the cortex before meiotic division.…”

“…Mouse oocytes injected with antibody against MOS failed to assemble a meiotic spindle [6]. In maturing mos -/-oocyte MAP kinase could not be activated throughout meiosis, which resulted in the shape alteration of spindle [7,8]. In mouse oocytes, MAP kinase is specifically associated with the microtubule-organizing centers (MTOCs) present at the spindle poles and in the cytoplasm [9], which suggests that MAP kinase might involve in controlling spindle assembly and microtubular configurations.…”