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Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disease caused by a deficiency of arylsulfatase B (ASB) which has its function in the sequential degradation of glycosaminoglycans (GAG). Targeted disruption of the ASB gene resulted in a mouse model of MPS VI that has been closely investigated for skeletal and chondral dysplasia. As ocular and cardiac impairment are also clinically important manifestations of the MPS VI syndrome, the present study was initiated for detailed biochemical, histologic and functional analysis of cornea, optic nerve and heart in ASB-deficient mice. Biochemical evidence for GAG-storage could be obtained for liver, kidney, spleen and myocardium as well as for heart valves, cornea and optic nerve from ASB-deficient mice. In MPS VI mice, histology revealed structural impairment of corneal stroma and epithelium as well as a thickening of the heart valves. According to histologic investigations, the optic nerve appeared not to be altered. However, GAG-storage in the dura mater could be demonstrated in MPS VI mice. Heart function was assessed by echocardiography. While the dimensions of MPS VI hearts were not altered, these hearts clearly showed decreased myocardial contraction and a 50% reduction of cardiac output. In addition, insufficiencies in the mitral and aortic valves were detected. Thus, ASBdeficient mice resemble the phenotype of human MPS VI not only in the skeletal but also in the ocular and cardiac symptoms. ASB is essential for desulfation of C4-linked sulfate esters from the non-reducing end of N-acetylgalactosamine residues in the glycosaminoglycans dermatan sulfate and chondroitin-4-sulfate (1). Consequently, mutation of the two ASB gene alleles results in impairment of glycosaminoglycan (GAG) degradation, subsequent lysosomal storage and urinary excretion of dermatan sulfate and other GAG species (2).The clinical course of MPS VI patients shows great variability in terms of the severity of symptoms and the age of onset of the disease (1

Apoptosis seems to play a role in follicular loss during ovarian transplantation; however, local application of S1P does not prevent primordial/primary follicles from hypoxia-induced cell death in cortical grafts in our study.

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Background: Fertility preservation by ovarian cryopreservation and heterotopic ovarian transplant is hampered by ischemic damage of the transplanted graft and poor oocyte viability. Design: Two longitudinal experiments were done-phase A: to evaluate if the administration of gonadotrophins (hMG) or vascular endothelial growth factor (VEGF) increases follicular survival after heterotopic autologous ovarian transplantation, and phase B: to determine if the administration of hMG enhanced neovascularization by increase in microvessel density in the heterotopic xenologous ovarian transplant. Methods: A: In three sheep, ovaries were removed and immediately transplanted into the abdominal wall. In one sheep, VEGF was administered at the transplantation site during surgery, the second was treated with hMG after transplantation for 2 weeks, and the third sheep served as control. B: The ovaries from two other sheep were removed, prepared in tissue pieces, and immediately grafted into the subcutaneous space of several combined immunodeficient (SCID-)mice (n = 20). Following the transplantation, 10 of these mice (group 1) were treated with hMG until they were sacrificed, the other 10 untreated mice (group 2) served as controls. In each group, two mice were sacrificed at intervals of 2, 4, 6, 10, and 14 days after grafting to permit histologic examination of the grafted tissue. Results: A: Whereas VEGF had no effect on follic-Zusammenfassung Einführung: Die Strategie der Kryokonservierung und Transplantation von ovariellem Gewebe bei malignomerkrankten Frauen zur Erhaltung der Fertilität beinhaltet die Problematik eines ausgeprägten ischämiebedingten Follikelverlustes. Fragestellung: Lässt sich durch die systemische bzw. lokale Applikation angiogeneseinduzierender Substanzen die (Neo-)Vaskularisation nach Transplantation verbessern bzw. der Follikel-Verlust reduzieren? Material und Methoden: A: Drei weiblichen Schafen wurden beide Ovarien explantiert, in 1 mm dicke Scheiben geschnitten und anschließend autolog heterotop in die Bauchwand retransplantiert. Bei einem Schaf wurde das ovarielle Gewebe im Rahmen der Transplantation lokal in eine VEGF (5 μg-)Fibrinkleber-Suspension eingebettet. Einem weiteren Schaf wurden über 2 Wochen nach Transplantation alle 2 Tage 150 IE/hMG systemisch appliziert. Das dritte Schaf blieb ohne Behandlung. Neun Monate später wurde das transplantierte Gewebe zur histologischen Analyse entnommen und das Follikelüberleben miteinander verglichen. B: Zwei weiteren Schafe wurden beide Ovarien explantiert, in entsprechende Scheiben präpariert, und in 20 immun-inkompetente Mäuse xenolog heterotop im Bereich des Rückens transplantiert. Zehn dieser Mäuse erhielten jeden 2. Tag 10 IE hMG systemisch beginnend ab dem Tag der Transplantation bis zur finalen Explantation. Die übrigen