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, Javier; Blohberger, Jan; Tiszavari, Michelle; Mayerhofer, Artur & Lara, Hernan E.
  
• 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, A. L.; Crestani, C. C.; Fernández‐Guasti, A.; Larco, D. O.; Mayerhofer, A. & Roselli, C. E.
  
• Human Luteinized Granulosa Cells-­A Cellular Model for the Human Corpus Luteum. Front Endocrinol (Lausanne). 2019 Jul 9;10:452
  Bagnjuk, Konstantin & Mayerhofer, Artur
  
• 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, Konstantin; Kast, Verena Jasmin; Tiefenbacher, Astrid; Kaseder, Melanie; Yanase, Toshihiko; Burges, Alexander; Kunz, Lars; Mayr, Doris & Mayerhofer, Artur
  
• Necroptosis in primate luteolysis: a role for ceramide. Cell Death Discov. 2019 Feb 11;5:67
  Bagnjuk, Konstantin; Stöckl, Jan Bernd; Fröhlich, Thomas; Arnold, Georg Josef; Behr, Rüdiger; Berg, Ulrike; Berg, Dieter; Kunz, Lars; Bishop, Cecily; Xu, Jing & Mayerhofer, Artur