Acetylcholine/acetylcholine esterase and necroptosis in the ovary

• Applicants: Professor Dr. Artur Mayerhofer; Professorin Dr. Doris Mayr
• Subject Area: Reproductive Medicine, Urology ; Gynaecology and Obstetrics
• Term: from 2011 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 195528179

• Final Report Year: 2020

Final Report Abstract

• We identified unknown actions of ACh in the ovary and GCs and linked them to trophic, fertility-promoting actions exerted mainly at the level of GCs. • We also delineated a natural pathway in GCs and in primate CL. It involves ceramides, which lead to necroptosis of human GCs and in primate CL. • Insights into induction of cell death in GC tumors were gained, involving a SMAC mimetic. • The project resulted in several publications and taken together, the new insights may help to improve the outcome of follicular cultures/therapies for GC tumors and ultimately may be used to design new therapeutic approaches. • The successful project together with only recently available data, have also ignited the interest in another important related facet of ACh-action, which is related to anti-inflammatory and protective actions in the ovary, topics not explored at all. A follow-up study recently received funding.

Publications

• In vivo blockade of acetylcholinesterase increases intraovarian acetylcholine and enhances follicular development and fertility in the rat. Sci Rep. 2016 Jul 21;6:30129
  Urra J, Blohberger J, Tiszavari M, Mayerhofer A, Lara HE
  
• Acetylcholine and necroptosis are players in follicular development in primates. Sci Rep. 2018 Apr 18;8(1):6166
  Du Y, Bagnjuk K, Lawson MS, Xu J, Mayerhofer A
  
• Neuropeptide and steroid hormone mediators of neuroendocrine regulation. J Neuroendocrinol. 2018 Oct;30(10):e12599
  Heck AL, Crestani CC, Fernández-­Guasti A, Larco DO, Mayerhofer A, Roselli CE
  
• Human Luteinized Granulosa Cells-­A Cellular Model for the Human Corpus Luteum. Front Endocrinol (Lausanne). 2019 Jul 9;10:452
  Bagnjuk K, Mayerhofer A
  
• Inhibitor of apoptosis proteins are potential targets for treatment of granulosa cell tumors -­ implications from studies in KGN. J Ovarian Res. 2019 Aug 14;12(1):76
  Bagnjuk K, Kast VJ, Tiefenbacher A, Kaseder M, Yanase T, Burges A, Kunz L, Mayr D, Mayerhofer A
  
• Necroptosis in primate luteolysis: a role for ceramide. Cell Death Discov. 2019 Feb 11;5:67
  Bagnjuk K, Stöckl JB, Fröhlich T, Arnold GJ, Behr R, Berg U, Berg D, Kunz L, Bishop C, Xu J, Mayerhofer A