Cited from CRU homepage:

2017 - 2020

Male Germ Cells: from Genes to Function - DFG Clinical Research Unit (CRU) 326

Male infertility is a genetically and clinically highly heterogeneous disease. Thus, unravelling the underlying causes and the pathophysiology is challenging and requires an integrated approach. To this end, we set up a Clinical Research Unit (CRU) that investigates in translational projects human male germ cell function from complete germ cell loss to sperm dysfunction at the genetic, epigenetic, and molecular level. In Münster, the setting to study male infertility is unique. On the campus, interdisciplinary expertise on the biology of male germ cells co-locates with major andrological, genetic, and stem cell institutions. Successful bilateral collaborations have already proven the potential for concerted basic, translational, and clinical research. However, to tap the full potential of this environment and to trigger synergies, it is required to intimately interconnect the institutions. Similarly, common animal models such as the zebrafish are still insufficiently used to gain insight into human male germ cell development und function.

To form this CRU, we joined clinical and basic research institutions that primarily study male germ cell function with institutions that primarily focus on stem cells, paediatrics, and powerful animal models. Thus, this CRU consists of the three layers basic science, a network of research projects, and clinical research. These are interconnected by the ‘DNA’, i.e. the concerted research on the epi-/genetics of male germ cells and the professorship of ‘Reproductive Genetics’. This novel position for the designated research coordinator Frank Tüttelmann is a unique feature of a Clinical Research Unit and one cornerstone of this endeavour. It is required to successfully initiate, coordinate, and develop this CRU and, most importantly, to sustain and drive research on male fertility and reproduction as a focus of the Medical Faculty beyond this CRU.

The seven research and one core projects are tightly interlinked and address a unifying hypothesis: A wide spectrum of leading pathologies with the common denominator of male infertility share common epi-/genetic causes. Improving phenotyping by interdisciplinary evaluation of patients, interconnecting basic and clinical research, and linking clinical to genome-wide data will elucidate novel distinct pathologies and their genetic basis.

To achieve the research goals, this CRU breaks current barriers between disciplines as well as basic science and clinical research. It will overcome the classical concept of male infertility as an isolated disease and create an integrated view allowing both forward (gene to patient) and reverse (patient to gene) approaches to identify novel epi-/genetic factors and associated phenotypes that impact germ cell function. This will significantly improve the diagnostic yield in infertile male patients and, ultimately, improve patient care.

2020+

Concept of the CRU326 Male Germ Cells: from Genes to Function

To date, infertile men are put into distinct and partially arbitrary categories such as 'oligozoospermia'. In contrast, our vision is to phenotype each patient in depth and identify specific causes of his infertility. This personalised approach will, subsequently, allow for individualised treatment. To achieve this comprehensive view, a number of tools and topics need to be taken into account and are central to this clinical research unit [..].

• We employ OMICs building on shared availability of data and samples, namely epi-/genetics, (single cell) transcriptomics, and pharmacogenetics.
• Multidisciplinarity is the keystone to tap the respective expertise and, thus, make it available across institutions and disciplines. A concrete measure is the perpetuation of the multidisciplinary case conferences.
• Special consultations for 'Unexplained Male Infertility' (CeRA), 'PCD and Infertility' (DGP), and 'Reproductive Genetics' (IHG) within the highly interconnected setting of this clinical research unit have been established and will be sustained.
• Novel andrological parameters including several non-standard tests (extended hormone profiles, DNA fragmentation index), semi-automated spermmorphology analysis, a CatSper-Activity-Test as well as data and DNA collection of family members will allow deep phenotyping of infertile men.

These measures taken together will significantly increase the rate of causal diagnoses. Thus, main added value of the CRU326 will be the multi-faceted, integrated approach to male infertility creating a sustained impact on research and clinic alike.