Campus

 

Stephen M. Downs

Wehr Distinguished Professor
Wehr Life Sciences, 513
(414) 288-1698
E-mail

B.A. 1975, Augustana College, Sioux Falls, SD
M.A.T. 1976, Augustana College, Sioux Falls, SD
Ph.D. 1982, University of Iowa, Iowa City, IA
Postdoctoral Fellow, Jackson Laboratory, Bar Harbor, ME

 

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.  We have also begun a careful comparison of meiotic regulation in mouse and rat oocytes, since initial work indicates profound differences between the two species.

 

Selected Publications

Ya, R. and Downs, S.M. 2013. Suppression of chemically induced and spontaneous mouse oocyte activation by AMP-activated protein kinase. Biol Reprod 88 (3): 70, 1-11.

Ya, R. and Downs, S.M. 2012. Perturbing microtubule integrity blocks AMP-activated protein kinase-induced meiotic resumption in cultured mouse oocytes. Zygote, available on CJO2012. doi:10.1017/S0967199412000457.

Downs, S.M.  2011.  Mouse versus rat: profound differences in meiotic regulation at the level of the isolated oocyte. Mol Reprod Dev 78: 778-794. .

Downs, S.M., Ya, R. and Davis, C.C.  2010.  Role of AMPK throughout meiotic maturation in the mouse oocyte: evidence for promotion of polar body formation and suppression of premature activation. Mol Reprod Dev 77: 888-899.

Downs, S.M.  2010. Regulation of the G2/M transition in rodent oocytes. Mol Reprod Dev 77: 566-585.

Downs, S.M., Mosey, J.L. And Klinger, J.  2009.  Fatty acid oxidation and meiotic resumption in mouse oocytes. Mol Reprod Dev 76: 844-853.

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 oocytes. 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 kinase and 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.

 

Awards

Wehr Distinguished Professorship (2008-  )

Lawrence G. Haggerty Faculty Award for Research Excellence (2009)

 

Current Students

Dr. Downs is NOT currently accepting new Ph.D. students into his lab

 



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Biological Sciences Department

Marquette University, Wehr Life Sciences
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