Jonathan Van Blerkom - Research Professor

The very early development of the
mammalian embryo is regulated in part by molecular
changes and cellular reorganizations established prior
to fertilization. Rapid changes in the patterns of
macromolecular syntheses and modification and in
the organization and structure of the cytoplasm and
plasma membrane occur during the terminal stages of
oogenesis, the period of resumed meiosis that
immediately precedes ovulation. Collectively, these
changes represent the expression of a developmental
program that prepares the oocyte for fertilization and
subsequent development. Research in this laboratory
has focused on the characterization of this
developmental program with respect to temporal
expression and coordination of molecular and
cellular differentiation of the preovulatory oocyte.
Recent findings indicate that a series of nuclear
signals may alter the cytoarchitecture of the ooplasm
and simultaneously initiate a cascade of protein
modifications. Alterations in the underlying structure
of the cytoplasm appear to (1) promote stage-specific
redistributions of organelles and (2) initiate
molecular changes required for fertilization. Current
research is directed toward understanding how a
molecular and cellular program of mammalian oocyte
development is regulated and coordinated during the
preovulatory stages of oogenesis.

Other research is examining the molecular
and cellula changes associated with oocyte
cryopreservation and the causes of the
developmental arrest at the 4-to-8 cell stage that
occurs at high frequency (>90%) in embryos
produced by older females (i.e., women over age
41). Oocyte cryopreservation is accompanied by
profound disruptions in cytoplasmic organization and
molecular expression. Because these alterations are
reversible after thawing and culture, however, this
system allows us to examine the process by which the
oocyte progressively reestablishes a normal nuclear
and cytoplasmic architecture, including specific
spatial distributions of organelles and
developmentally critical proteins. Our studies of
developmental failure in human reproduction indicate
both genetic and nongenetic etiologies. Insufficient
ATP production appears to be a significant factor
contributing to developmental failure during the early
post-fertilization period, while developmental failure
of older embryos appears to be primarily associated
with genetic abnormalities. Some of our current
efforts include (1) the identification of genomic
signals associated with mitochondria activation and
(2) whether oocytes from older females can be
rescued from premature developmental arrest by
repopulation with mitochondria isolated from the
oocytes of young mice.