Endocrine Abstracts (2016) 41 EP711 | DOI: 10.1530/endoabs.41.EP711

Altered testicular vascularization and impaired blood supply in the 41,XXY* mouse model for Klinefelter syndrome

Cristin Brand1, Oliver S Damm1, Ann-Sophie Warmeling1, Reinhild Sandhowe-Klaverkamp1, Steffi Werler1, Katharina Koerner1, Joerg Stypmann2, Michael Kuhlmann3, Richard Holtmeier3, Michael Zitzmann4, Frank Tuettelmann5, Joerg Gromoll1 & Joachim Wistuba1

1Institute of Reproductive and Regenerative Biology, Centre of Reproductive Medicine and Andrology, University of Muenster, Muenster, NRW, Germany; 2Department of Cardiovascular Medicine, University of Muenster, Muenster, NRW, Germany; 3European Institute for Molecular Imaging, University of Muenster, Muenster, NRW, Germany; 4Department of Clinical Andrology, Centre of Reproductive Medicine and Andrology, University of Muenster, Muenster, NRW, Germany; 5Institute of Human Genetics, University of Muenster, Muenster, NRW, Germany.

Intratesticular testosterone levels in Klinefelter syndrome (KS) are comparable to controls and Leydig cell function was proven to be normal at least in vitro, testicular vascularization changes came into focus as a potential factor contributing to hypogonadism. We performed enhanced ultrasound based analysis of the testicular blood support in our 41,XXY* mice. Adult male 41,XXY* (n=5) and control mice (n=6) underwent ultrasound analyses with the Non-Targeted Contrast Agent Vevo MicroMarker. The agent containing gas filled micro-bubbles was administered intravenously (lower body perfusion). After initial perfusion, micro-bubbles were destroyed by high ultrasound pressure and the reperfusion period was analysed. In parallel, electrocardiograms (ECGs) were taken. Afterwards mice were sacrificed and testes removed for histological analysis of vascularization. Whilst ECGs did not reveal differences in heart function, the reperfusion time for testes was significantly increased in 41,XXY* mice (XXY* 28.8±1.7 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. Testicular bIood vessel areas of adult males were assigned to four categories (I=<80 μm2, II=80–1000 μm2, III=1000–5062 μm2, IV=>5062 μm2). The blood vessel area of categories I and II was significantly decreased in 41,XXY* mice (P<0.0001). Taking the testis area into account, the area covered by vessels of category II and III is significantly elevated in KS mice. Blood vessels of category IV were missing in KS testes. These functional and morphological data strengthen the assumption that the observation made previously contributes to the endocrine phenotype seen in KS pointing to an affected vascular system in the disturbed testicular tissue of males with supernumerary X.