Unravelling the mechanisms of azoospermia and potential future treatments in male cystinosis patients

Cystinosis is a rare inheritable disorder in which cystine, a small protein, accumulates in all cells throughout the body. Patients suffer from progressive renal failure due to extensive proximal tubular and glomerular dysfunction, but also various endocrine organs become affected later in life. Patients can be treated with cysteamine, a drug which breaks down the cystine in two smaller products which can be eliminated by each cell. Cysteamine has proven to postpone the renal function deterioration, and endocrine organ dysfunction. Until now, no pregnancy induced by male cystinosis patient has been reported in literature. A substantial proportion of male cystinosis patients shows primary testicular failure, but there are also patients in which testicular function and sex hormone homeostasis is preserved. However, in a recent report on fertility in male cystinosis patients, a complete absence of spermatozoa (azoospermia) has been documented in the ejaculated semen of all male cystinosis patients examined. On the other hand, we have documented that spermatogenesis on the testicular level remained intact in one investigated case. The epididymis plays an important role in sperm maturation, and shows similar processes of electrolyte and water reabsorption as those present in the renal proximal tubules which are defective in these patients. There is also evidence that cysteamine may have an effect on sex hormone levels, spermatogenesis and epididymal sperm maturation. In this study we would first like to rule out a potential obstructive cause for this azoospermia in cystinosis males. Further on, we would like to investigate the electrolyte composition of the epididymal luminal fluid in human subjects and a murine model, and assess the potential effect of cysteamine on spermatogenesis in a murine model. Additionally, we will perform a systematic histopathological analysis of human testicular tissue and preserve testicular and epididymal sperm for potential future assisted reproduction techniques (ART). Our ultimate aim is to generate knowledge and technology to create the possibility of pregnancy induction by male cystinosis patients.


Award Date
30 June 2016
Award Value
Principal Investigator
Professor Elena Levtchenko
Host Institution
Katholieke Universiteit Leuven
MRCG-HRB Joint Funding Scheme