STEPHEN M. DOWNS 
Professor 

B.A. 1975, Augustana College (South Dakota)
M.A.T. 1976, Augustana College (South Dakota)
Ph.D. 1982, University of Iowa
Postdoctoral Training, Jackson Laboratory

WLS 308
(414) 288-1698
email: stephen.downs@marquette.edu

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The Control of Mammalian Oocyte Maturation

Work in this laboratory focuses on chemical mediators and mechanisms involved in the control of meiotic maturation in the mammalian oocyte. We have identified purines within the ovarian follicle that play an important role in the meiotic-arresting and –inducing mechanisms that regulate oocyte maturation. We have also examined how energy substrates affect meiosis, including their metabolic routes and interaction with purine metabolic pathways. Because of the importance of glucose in meiotic control, we have tested the effects of experimentally induced diabetes on oocyte maturation and find serious defects in metabolism and meiotic regulation. Cyclic adenosine monophosphate, or cAMP, is an important regulatory molecule that exerts both positive and negative actions on meiotic maturation. We are currently investigating how fluctuations in the levels of this important second messenger within the oocyte relate to meiotic regulation. A recent subject of interest is the possible involvement of the stress-response kinase, AMP-activated protein kinase (AMPK), in meiotic control. We have reported that AMPK is present in mouse oocytes and that its activation is associated with the meiosis-inducing action of the adenosine analog, AICA riboside. Recent results indicate the AMPK plays a physiological role in regulating oocyte maturation in mice. Since AMPK activation leads to stimulation of fatty acid oxidation, we are currently investigating to what extent this metabolic pathway is involved in meiotic induction in mice. Additional studies center on a possible role for AMPK in meiotic induction induced by physical, chemical and metabolic stress as well as the importance of AMPK throughout oocyte maturation and preimplantation embryo development.

Selected references:

Chen, J. and Downs, S.M.  2008.  AMP-activated protein kinase is involved in hormone-induced mouse oocyte meiotic maturation in vitro. Dev Biol 313: 47-57.

Downs, S.M. and Chen, J.  2008.  EGF-like peptides mediate FSH-induced maturation of cumulus cell-enclosed mouse ocoytes. Mole Reprod Dev 75: 105-114.

LaRosa, C. and Downs, S.M.  2007.  Meiotic induction by heat stress in mouse oocytes: involvement of AMP-activated protein kinaseand MAPK family members. Biol Reprod 76: 476-486.

Chen, J., Hudson, E., Chi, M.M., Chang, A.S., Moley, K.H., Hardie, D.G., and Downs, S.M.  2006.  AMPK regulation of mouse oocyte meiotic resumption in vitro. Dev. Biol: 291: 227-238.

LaRosa, C. and Downs, S.M.  2005.  MEK inhibitors block AICAR-induced meiotic resumption in mouse oocytes by a MAPK-independent mechanism. Mol Reprod Dev 70: 235-245.

Colton, S.A. and Downs, S.M.  2004.  Potential role for the sorbitol pathway in the meiotic dysfunction exhibited by oocytes from diabetic mice. J Exp Zool 301A: 439-448.

Colton, S.A., Humpherson,  P.G., Leese, H.J., and Downs, S.M.  2003.  Physiological changes in oocyte-cumulus cell complexes from diabetic mice that potentially influence meiotic regulation. Biol Reprod 69: 761-770.

Downs, S.M. and Verhoeven, A.  2003.  Glutamine and the maintenance of meiotic arrest in mouse oocytes: influence of culture medium, glucose, and cumulus cells. Mol Reprod Dev 66: 90-97.

Downs, S.M., Hudson, E.R., and Hardie, D.G.  2002.  A potential role for AMP-activated protein kinase in meiotic induction in mouse oocytes. Dev Biol 245: 200-212.

Colton, S.A., Pieper, G.M., and Downs, S.M.  2002.  Altered meiotic regulation in oocytes from diabetic mice. Biol Reprod 67: 220-231.

Downs, S.M., Humpherson, P.G. and Leese, H.J.  1998.  Meiotic induction in cumulus cell-enclosed mouse oocytes: involvement of the pentose phosphate pathway. Biol Reprod 58: 1084-1094.