00 +/�?0.991 0.93 +/�?0.144 DHL 6 0.47 +/�?0.18 4.5 +/�?0.71 0.51 +/�?0.13 0.74 0.56 +/�?0.055 L1236 0.60 +/�?0.08 N.D. N.D. 0.36 +/�?0.003 0.69 +/�?0.078 U937 1.50 +/�?0.14 0.44 +/�?0.16 1.27 +/�?0.42 0.65 +/�?0.144 0.85 Cancer Res. Author manuscript, available in PMC 2012 June 1. Aurora Kinase B Modulates Chromosome Alignment in Mouse Oocytes mk-2866 Androgen Receptor inhibitor KRISTY SHUDA1,2, KAREN SCHINDLER3, JUN MA3, RICHARD M. SCHULTZ3,*, and PETER J. DONOVAN4,** 1Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 2Biology Department, Community College of Philadelphia, Philadelphia, Pennsylvania 3Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 4Sue and Bill Gross Stem Cell Research Program, Departments of Developmental and Cell Biology and Biological Chemistry, University of California, Irvine, Irvine, California SUMMARY The elevated incidence of aneuploidy in human oocytes warrants study of the molecular mechanisms regulating proper chromosome segregation.
The Aurora kinases OSI-930 728033-96-3 are a well conserved family of serine/threonine kinases that are involved in proper chromosome segregation during mitosis and meiosis. Here we report the expression and localization of all three Aurora kinase homologs, AURKA, AURKB, and AURKC, during meiotic maturation of mouse oocytes. AURKA, the most abundantly expressed homolog, localizes to the spindle poles during meiosis I and meiosis II , whereas AURKB is concentrated at kinetochores, specifically at metaphase of MI . The germ cell specific homolog, AURKC, is found along the entire length of chromosomes during both meiotic divisions.
Maturing oocytes in the presence of the small molecule pan Aurora kinase inhibitor, ZM447439 results in defects in meiotic progression and chromosome alignment at both Met I and Met II. Over expression of AURKB, but not AURKA or AURKC, rescues the chromosome alignment defect suggesting that AURKB is the primary Aurora kinase responsible for regulating chromosome dynamics during meiosis in mouse oocytes. INTRODUCTION In humans, 1 4% of sperm from healthy human males are aneuploid , whereas approximately 20% of human oocytes are aneuploid . If an aneuploid gamete fertilizes or is fertilized by a gamete of the opposite sex, the resulting aneuploid preimplantation embryo may fail to develop or implant .
If implantation occurs, the embryo may undergo spontaneous abortion , and if development goes to term, congenital disorders may be observed . This difference in aneuploidy incidence most likely involves the difference in timing of meiosis between the two sexes. Males undergo spermatogenesis continuously beginning at puberty with a stem cell population generating the supply of male germ cells that continuously give rise to © 2009 WILEY LISS, INC. *Corresponding author: Department of Biology University of Pennsylvania 433 S. University Ave Philadelphia, PA 19104. rschultzsas.upenn . **Corresponding author: Departments of Developmental and Cell Biology and Biological Chemistry University of California 2501 Hewitt Hall, Irvine, CA 92697. pdonovanuci . Kristy Shuda and Karen Schindler contributed equally to this work. NIH Public Access Author Manuscript Mol Reprod Dev.
Author manuscript, available in PMC 2011 October 5. Published in final edited form as: Mol Reprod Dev. 2009 November , 76: 1094 1105. doi:10.1002/mrd.21075. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript daughter cells that undergo meiosis. In contrast, oocytes in females enter the first meiotic prophase during fetal life and the female is born with the full complement of oocytes that are contained in primordial follicles and become arrested in the dictyate stage of meiosis I . In humans, the onset of puberty initiates both growth of primordial oocytes and resumption of meiosis in response to a gonadotropin surge. The ovulated oocytes arrest at metaphase II , and only complete the second meiotic division upon fertilization. Accurate chromosom