Fatty Acid Metabolism and Meiotic Resumption in Mammalian Oocytes

Jon Klinger
Marquette University
Mentor: Dr. Stephen Downs

At birth, mouse oocytes are arrested in prophase I of meiosis.  Gonadotropins, originating from the anterior pituitary, stimulate the release of oocytes from ovaries and induce meiotic maturation.  The lab has previously done studies on a stress-sensing enzyme called AMP-Activated Protein Kinase (AMPK).  Stimulation of AMPK by and adenosine analog, AICA riboside (AICAR), has been shown to induce resumption of maturation in mouse oocytes.  When activated, AMPK will stimulate energy-producing pathways and inhibit energy-consuming pathways.  One of the pathways stimulated by AMPK is fatty acid oxidation.  This led us to investigate the involvement of fatty acid metabolism in meiotic arrest.

A synthetic compound called C75 has been shown to have an effect on fatty acid metabolism in rodents. C75 acts on fatty acid metabolism in two ways.  First, it activates a key regulator of fatty acid oxidation called Carnitine Palmitoyltransferase-1 (CPT-1), and stimulates the breakdown of fatty acids.  Secondly, C75 inhibits a key enzyme in fatty acid synthesis called Fatty Acid Synthase (FAS), and inhibits fatty acid synthesis.  C75 can stimulate meiotic resumption in various inhibiting conditions.  Several experiments were performed to investigate this further.  A second inhibitor of FAS, Cerulenin, stimulated meiotic maturation but much less effectively than C75.  An inhibitor of CPT-1 and fatty acid oxidation, Etomoxir, significantly inhibited C75-induced meiotic maturation.  Data suggests that fatty acid oxidation is the principle means by which C75 is acting on oocytes to stimulate meiotic resumption. These results strongly implicate fatty acid metabolism in the regulation of mouse oocyte maturation.
 
 
 

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