Exp Clin Endocrinol Diabetes 2015; 123 - P11_09
DOI: 10.1055/s-0035-1547734

Contrast enhanced ultrasound confirms testicular circulation to be hampered by disturbed vascularization in 41, XXY* mice, a model for Klinefelter syndrome

OS Damm 1, AS Warmeling 2, R Sandhowe-Klaverkamp 1, S Werler 3, K Körner 4, J Stypmann 5, M Kuhlmann 6, R Holtmeier 7, M Zitzmann 8, F Tüttelmann 9, J Gromoll 1, J Wistuba 1
  • 1Centrum für Reproduktionsmedizin und Andrologie, Universität Münster; Cera
  • 2Centrum für Reproduktionsmedizin und Andrologie, Universität Münster; Cera
  • 3Centrum für Reproduktionsmedizin und Andrologie, Universität Münster; Institute of Reproductive and Regenerative Biology
  • 4Centrum für Reproduktionsmedizin und Andrologie, Universität Münster; Cera
  • 5Department of Cardiovascular Medicine; University of Münster
  • 6European Institute for Molecular Imaging (Eimi); University of Muenster
  • 7European Institute for Molecular Imaging (Eimi); University of Münster
  • 8Universitätsklinikum Münster; Cera
  • 9Institute of Human Genetics; University of Münster

Testosterone deficiency in Klinefelter syndrome (KS) was thought to result from disturbed Leydig cell (LC) function. However, in a KS mouse model (41,XXY*), LCs were found to be hyperplastic and hyper-reactive. Furthermore, intratesticular testosterone (ITT) concentrations were comparable to controls with a normal karyotype. We confirmed this in a cohort of patients, excluding insufficient ITT levels as the cause of hypogonadism. It was reported that arteries in KS patients are altered and circulation impaired. Changes in testicular vascularization were also found previously in the 41,XXY* mouse model. We hypothesize disturbed testicular blood supply might be involved in the endocrine phenotype. We therefore performed a study in which an enhanced ultrasound based analysis of the testicular blood flow rate in 41,XXY* mice was conducted. Adult male 41,XXY* (n = 5) and littermate mice (n = 6) underwent ultrasound analyses with the Non-Targeted Contrast Agent Vevo MicroMarker. The agent containing gas filled micro-bubbles was administered intravenously for lower body perfusion. After initial perfusion, micro-bubbles were destroyed by high ultrasound pressure and the reperfusion period was documented and analysed. In parallel, electrocardiograms (ECGs) were taken. Afterwards mice were sacrificed and testes removed for histological analysis of the vascularization. Whilst ECGs did not reveal differences in heart function between the groups, the reperfusion time for testes was significantly increased in 41,XXY* mice (XXY* 28.8 ± 1.69 s; XY* 19.9 ± 2.8 s) Testes of 41,XXY* mice (XXY* 4.6 ± 0.10 mm2; XY* 11.1 ± 0.34 mm2) and the area covered by blood vessels (XXY* 0.025 ± 0.003 mm2; XY* 0.040 ± 0.002 mm2) were significantly smaller as revealed by histology. Conclusively, our data indicate an impaired blood flow in testes of males with a supernumerary X chromosome, which might contribute to the endocrine phenotype of KS.