Our lab studies questions in human reproductive biology and reproductive medicine. Our current research is focused on peritubular cells of the testis and ovarian granulosa cells as models for the human gonads.
We collaborate with scientists and clinicians in Germany. Our international partners are located in Finland, Chile, Argentina, Israel and the United States. Our interdisciplinary approaches include cellular/molecular biological and morphological methods. We are supported by the German Research Foundation (DFG), DAAD (Deutscher Akademischer Austauschdienst) and GIF (German-Israeli Foundation).
Research Areas (October 2017):
1. Testicular peritubular cells, testicular ageing and inflammation:
Peritubular cells form the wall of the seminiferous tubules in the testis. Although they are regarded as contractile myofibroblasts, their precise functions are largely unknown. Investigations of our group provide evidence for a role in the control of spermatogonial stem cells. For example, they produce an important growth factor (GDNF), which regulates these stem cells, and PEDF, which among others may be the key to the question why seminiferous tubules are avascular. By analyzing the secretory characteristics of the peritubular cells we aim to elucidate how they contribute to the microenvironment of the human testis. In addition, we found that the wall of the seminiferous tubule may host progenitor cells or even stem cells for Leydig cells. Ongoing work studies the questions, whether and how peritubular cells may age and whether this may contribute to testicular ageing. Funding: DFG MA 1080/27-1; The role of testicular peritubular cells in human testicular ageing; head of project: Prof. Artur Mayerhofer; partners: Dr. Georg Arnold, Gene Center, LMU Munich and Prof. Rüdiger Behr, DPZ, Göttingen
Male infertility is often associated with changes of the extracellular matrix of the tubular wall and with signs of inflammation. The extracellular matrix components decorin and biglycan, as well as testicular mast cells and their products, are in the focus of our interest. Decorin can affect the actions of growth factors and is produced by peritubular cells, and as we found by ovarian cells, as well. Biglycan, the sister molecule of decorin, may play a role in testicular inflammatory events, often witnessed in male infertility. We found, for example, that it can act as a danger molecule, acting via Toll like receptors to foster inflammation in peritubular cells. Our research attempts to better understand whether and how decorin and biglycan act. Funding: DFG MA1080/23-1; The role of the extracellular matrix molecule biglycan in non-infectious inflammation of the testis and male infertility; head of project: Prof. Artur Mayerhofer
In collaboration with Prof. Matti Poutanen and his group (University of Turku, Finland) we explore new research topics, related to male infertility. Funding: DAAD: PPP-program (Finland) Project 57347353
Mayer C, Adam M, Glashauser L, Dietrich K, Schwarzer JU, Köhn FM, Strauss L, Welter H, Poutanen M, Mayerhofer A. Sterile inflammation as a factor in human male infertility: Involvement of Toll like receptor 2, biglycan and peritubular cells. Sci Rep. 2016 Nov 16;6:37128.
Windschüttl S, Kampfer C, Mayer C, Flenkenthaler F, Fröhlich T, Schwarzer JU, Köhn FM, Urbanski H, Arnold GJ, Mayerhofer A. Human testicular peritubular cells secrete pigment epithelium-derived factor (PEDF), which may be responsible for the avascularity of the seminiferous tubules. Sci Rep. 2015 Sep 3;5:12820.
Landreh L, Spinnler K, Schubert K, Häkkinen MR, Auriola S, Poutanen M, Söder O, Svechnikov K, Mayerhofer A. Human testicular peritubular cells host putative stem Leydig cells with steroidogenic capacity. J Clin Endocrinol Metab. 2014 Jul;99(7):E1227-35.
Flenkenthaler F, Windschüttl S, Fröhlich T, Schwarzer JU, Mayerhofer A, Arnold GJ. Secretome analysis of testicular peritubular cells: a window into the human testicular microenvironment and the spermatogonial stem cell niche in man. J Proteome Res. 2014 Mar 7;13(3):1259-69.
Welter H, Huber A, Lauf S, Einwang D, Mayer C, Schwarzer JU, Köhn FM, Mayerhofer A. Angiotensin II regulates testicular peritubular cell function via AT1 receptor: a specific situation in male infertility. Mol Cell Endocrinol. 2014 Aug 5;393(1-2):171-8.
Mayerhofer A. Human testicular peritubular cells: more than meets the eye. Reproduction. 2013 Apr 29;145(5):R107-16.
Spinnler K, Köhn FM, Schwarzer U, Mayerhofer A. Glial cell line-derived neurotrophic factor is constitutively produced by human testicular peritubular cells and may contribute to the spermatogonial stem cell niche in man. Hum Reprod. 2010 Sep;25(9):2181-7.
2. Ovarian factors and granulosa cells
A second focus of our research is on local messengers in the ovary. Acetylcholine but also catecholamines, as well as reactive oxygen species (ROS) are in the center of the ongoing projects. High levels of the later are found in the ovary and are associated with pathologies, including polycystic ovary syndrome (PCOS) and possibly granulosa cell tumors. During these studies we discovered among others regulated necrosis (“necroptosis”) in the ovary. We also pinpoint trophic functions of acetylcholine in ovarian functions.
Funding: DFG MA 1080/26-1: Role of ROS in the signaling pathway of FSH and other ovarian factors; head of project: Prof. Artur Mayerhofer; Co-PI: PD. Dr. Lars Kunz, Biology, LMU Munich; DFG MA 1080/19-2: Acetylcholine/acetylcholinesterase and necroptosis in the ovary; head of project: Prof. Artur Mayerhofer; Co-PI: Prof. Doris Mayr, Pathology, LMU Munich;
In collaboration with Prof. Rina Meidan (Jerusalem, Israel) we will explore the role of sirtuin-1 in ovarian physiology and pathology. Funding: GIF Grant No. I-1417-201.2/2017: Role of sirtuins in human ovarian dysfunction (Polycystic ovary syndrome and cancer); head of project in Germany: Prof. Artur Mayerhofer; Co-PI: Prof. Doris Mayr, Pathology, LMU Munich;
Urra J, Blohberger J, Tiszavari M, Mayerhofer A, Lara HE. In vivo blockade of acetylcholinesterase increases intraovarian acetylcholine and enhances follicular development and fertility in the rat. Sci Rep. 2016 Jul 21;6:30129.
Blohberger J, Kunz L, Einwang D, Berg U, Berg D, Ojeda SR, Dissen GA, Fröhlich T, Arnold GJ, Soreq H, Lara H, Mayerhofer A. Readthrough acetylcholinesterase (AChE-R) and regulated necrosis: pharmacological targets for the regulation of ovarian functions? Cell Death Dis. 2015 Mar 12;6:e1685.
Barra R, Cruz G, Mayerhofer A, Paredes A, Lara HE. Maternal sympathetic stress impairs follicular development and puberty of the offspring. Reproduction. 2014Aug;148(2):137-45.
Saller S, Kunz L, Berg D, Berg U, Lara H, Urra J, Hecht S, Pavlik R, Thaler CJ, Mayerhofer A. Dopamine in human follicular fluid is associated with cellular uptake and metabolism-dependent generation of reactive oxygen species in granulosa cells: implications for physiology and pathology. Hum Reprod. 2014 Mar;29(3):555-67.
Saller S, Merz-Lange J, Raffael S, Hecht S, Pavlik R, Thaler C, Berg D, Berg U, Kunz L, Mayerhofer A. Norepinephrine, active norepinephrine transporter, and norepinephrine-metabolism are involved in the generation of reactive oxygen species in human ovarian granulosa cells. Endocrinology. 2012 Mar;153(3):1472-83.
Spinnler K, Fröhlich T, Arnold GJ, Kunz L, Mayerhofer A. Human tryptase cleaves pro-nerve growth factor (pro-NGF): hints of local, mast cell-dependent regulation of NGF/pro-NGF action. J Biol Chem. 2011 Sep 9;286(36):31707-13.
News and information:
Professor Artur Mayerhofer was (re)elected “DFG-Fachkollegiat für Reproduktionsbiologie/- Medizin” (Study Section ‘Medicine” of the German Research Council; first term 2012-2015; second term 2016-2020)
A new, 4th edition of Thieme, “Anatomie”, Duale Reihe, appeared in September 2017. Together with Prof. Katharina Spanel-Borowski, Prof. Artur Mayerhofer is author of Chapter 2: “Zytologie und Histologie - Grundlagen”