Molecular Human Reproduction, Vol 4, 745-756, Copyright © 1998 by Oxford University Press
O Heikinheimo and WE Gibbons
The purpose of the present review is to outline the current understanding
on the molecular mechanisms governing various stages of oocyte maturation,
transition from maternal to embryonic control and the initial steps of
pre-embryo development. The cytoplasmic and nuclear maturation of the
oocyte during pre-ovulatory development can be viewed as separate entities.
Cytoplasmic maturation and the acquisition of stores of RNA and protein
dominates oocyte development between the premordial and pre-ovulatory
stages of development. Initiation of nuclear maturation is marked by the
breakdown of the nuclear envelope, or germinal vesicle and is triggered by
the midcycle luteinizing hormone peak. In vitro, this is associated with a
decrease in the intracellular concentrations of cAMP. This and several
subsequent steps of meiosis are controlled by the M-phase promoting factor
(MPF). While the constituents of MPF, p34cdc2 kinase and B-type cyclin, are
also present in mitotically dividing cells, in meiotically dividing oocytes
the regulation of MPF activity differs. An oocyte- specific protein kinase,
c-mos, plays an important role in up- regulating the activity of MPF at
various stages of final oocyte maturation. Several lines of evidence
suggest that the proper function of the c-mos-MPF system is associated with
important features of the last stages of oocyte maturation such as the
resumption of meiotic maturation, inhibition of DNA replication between
meiosis I and II, and the maintenance of the oocyte at metaphase II arrest
until it is fertilized. Eventually the destruction of c-mos and active MPF
following fertilization allows the initiation of mitotic cell division in
the pre-embryo. The very first cell divisions of the human pre- embryo are
still under the control of maternally inherited mRNA and protein. Several
lines of evidence suggest that in humans, zygotic gene expression is
initiated between the 4- and 8-cell stages, after which the pre-embryo
begins to utilize its own genes. Some of the first genes to be expressed in
the human pre-embryo encode proteins that are associated with cell
division, extracellular growth modulatory signals as well as factors
associated with implantation. We acknowledge that most of the data
presented comes from species other than human, therefore at present the
full biological role of the proposed regulatory pathways and control
mechanisms for human biology remains speculative.
REVIEW, TUTORIAL
The molecular mechanisms of oocyte maturation and early embryonic development are unveiling new insights into reproductive medicine
Department of Biomedicine, University of Helsinki, Finland. Oskari.Heikinheimo@Helsinki.Fi
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