Jonathan Van Blerkom
Phone: 303) 492-6664
Ph.D., University of Colorado at Boulder, 1974
Regulation of oogenesis and early mammalian embryogenesis by genomic and extragenomic factors.
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.
DNA strand breaks and phosphatidylserine redistribution in newly ovulated and cultured mouse and human oocytes: occurrence and relationship to apoptosis.
Van Blerkom, J and Davis, PW Hum Reprod, 13(5):1317-24. 1998
Oocyte influences on early development: the regulatory proteins leptin and STAT3 are polarized in mouse and human oocytes and differentially distributed within the cells of the preimplantation stage embryo.
Antczak, M and Van Blerkom, J Mol Hum Reprod, 3(12):1067-86. 1997
The expression of leptin and its receptors in pre-ovulatory human follicles.
Cioffi, JA, Van Blerkom, J, Antczak, M, Shafer, A, Wittmer, S, and Snodgrass, HR Mol Hum Reprod, 3(6):467-72. 1997
The developmental potential of the human oocyte is related to the dissolved oxygen content of follicular fluid: association with vascular endothelial growth factor levels and perifollicular blood flow characteristics.
Van Blerkom, J, Antczak, M, and Schrader, R Hum Reprod, 12(5):1047-55. 1997
The fine structural development of preimplantation mouse parthenotes.
Van Blerkom, J and Runner, MN J Exp Zool, 196(1):113-24. 1976