Project Details
KFO 181: Male Factor Infertility due to Impaired Spermatogenesis
Subject Area
Medicine
Term
from 2008 to 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 34016037
The Clinical Research Unit aims at improving our knowledge on molecular mechanisms crucial to the regulation of spermatogenesis and possible reasons for deregulation in impaired spermatogenesis. In addition, the Clinical Research Unit will improve the diagnosis of idiopathic male infertility, as well as the cooperation between clinicians and basic researchers and provide talented junior scientists an exciting scientific environment where they can develop. Six projects each examine a different yet complementary facet of the overall problem.
Project 1 investigates chromatin stability in haploid germ cells and its impact on male fertility analysing the possible functional role of acetylated histones H3/H4 in spermatozoa for fertilisation and early embryogenesis.
Project 2 focuses on the Sertoli cell specific androgen receptor (AR) investigating possible links between AR polymorphism due to somatic CAG repeat mosaicism and AR-dependent TGF-?s and impaired spermatogenesis.
Project 3 investigates specific functions of peroxisomes in distinct testicular cell types for male fertiliy. Sertoli cell specific conditional PEX13 knockout mice will be used to analyse testicular dysfunction resulting from peroxisome deficiency and leading to infertility.
Project 4 focuses on the role of contractile cells that are involved in the transport of spermatozoa from the testis to the epididymis analysing phosphodiesterases (PDEs) and cGMP pathway.
Project 5 focuses on the identification of key molecules involved in the interplay between testicular cells and uropathogenic E. coli (UPEC), the most important bacterium for urogenital tract infections and infection based asymptomatic male infertility.
Project 6 investigates the functional significance of connexin 43 involved in Sertoli-Sertoli and Sertoli-germ cell contacts applying a Sertoli cell-specific knockout mouse model.
The originality of the Clinical Research Unit relies in the fact that, in this research network, the translation from fundamental work from mainly rodent models to the situation in the human will be realised using a large testicular biopsy repository and cryobank.
Project 1 investigates chromatin stability in haploid germ cells and its impact on male fertility analysing the possible functional role of acetylated histones H3/H4 in spermatozoa for fertilisation and early embryogenesis.
Project 2 focuses on the Sertoli cell specific androgen receptor (AR) investigating possible links between AR polymorphism due to somatic CAG repeat mosaicism and AR-dependent TGF-?s and impaired spermatogenesis.
Project 3 investigates specific functions of peroxisomes in distinct testicular cell types for male fertiliy. Sertoli cell specific conditional PEX13 knockout mice will be used to analyse testicular dysfunction resulting from peroxisome deficiency and leading to infertility.
Project 4 focuses on the role of contractile cells that are involved in the transport of spermatozoa from the testis to the epididymis analysing phosphodiesterases (PDEs) and cGMP pathway.
Project 5 focuses on the identification of key molecules involved in the interplay between testicular cells and uropathogenic E. coli (UPEC), the most important bacterium for urogenital tract infections and infection based asymptomatic male infertility.
Project 6 investigates the functional significance of connexin 43 involved in Sertoli-Sertoli and Sertoli-germ cell contacts applying a Sertoli cell-specific knockout mouse model.
The originality of the Clinical Research Unit relies in the fact that, in this research network, the translation from fundamental work from mainly rodent models to the situation in the human will be realised using a large testicular biopsy repository and cryobank.
DFG Programme
Clinical Research Units
Projects
- Analysis of androgen- and TGF-beta-regulated proteins in Sertoli cells (Applicant Konrad, Lutz )
- Atherosclerosis-related disturbances of spermatogenesis: lessons from the ApoE'^VLDL receptor'^' knockout mouse model and prospective investigations in men (Applicants Linn, Thomas ; Middendorff, Ralf ; Weidner, Wolfgang )
- Effects of a Sertoli cell specific knockout of the connexin43-gene on the regulation of spermatogenesis in transgenis mice using the Cre/IoxP-recombination system (Applicant Brehm, Ralph )
- Impact of peroxisomal metabolism in germ and Leydig cells on overall testis functions and male fertility (Applicant Baumgart-Vogt, Eveline )
- Impact of peroxisomal metabolism in germ and Leydig cells on overall testis functions and male fertility (Applicant Lüers, Georg )
- Key genetic and epigenetic factors contributed from male germ cell to early embryo: a novel bovine model (Applicant Schagdarsurengin, Undraga )
- Malefactor infertility due to impaired spermatogenesis (Applicant Steger, Klaus )
- Mechanism of impairment of testicular function by immune evasive mechanism of uropathogenic Escherichia coli (UPEC) (Applicants Chakraborty, Trinad ; Meinhardt, Andreas )
- Sperm histone code and epigenetic-mediated subfertility (Applicant Steger, Klaus )
- TAF4l3-dependent transcription and its relevance for male fertility in humans (Applicant Pütz-Rathke, Christina )
- The peritubular lamina propria testis and male Infertility: Relevance of contractility and fibrosis (Applicant Middendorff, Ralf )
Spokesperson
Professor Dr. Wolfgang Weidner
Leader
Professor Dr. Klaus Steger