MECHANISMS OF MALE INFERTILITY
|Medical Faculty of the Justus Liebig University Giessen
Department of Urology, Pediatric Urology and Andrology
Speaker: Prof. Dr. med. Wolfgang Weidner
Project Head: Prof. Dr. rer. nat. Klaus Steger
|Faculty of Biology of the Philipps University Marburg
INFERTILITY affects approximately one in six couples worldwide. While the nature and exact proportion of the predominant cause of the problem remains controversial, the World Health Organization (WHO) reports that in nearly 40% of cases the cause can be attributed to the female, in 20% to the male and in 25% to both, however, in 15% the cause still remains unknown (idiopathic infertility). Approximately half of infertile men are unable to father children without some form of assisted reproductive technology (ART) technique. At present, pregnancy rates associated with the most successful ART, intracytoplasmic sperm injection (ICSI), are fairly constant at approximately 25% live births per cycle, an outcome that is put into perspective when we consider the cost of a 75% failure rate in psychological and financial terms to the couples undergoing the treatment. The major shortcoming of available ART, however, is the need to treat the female partner for what is essentially a male problem.
IMPAIRED SPERMATOGENESIS can result from a variety of causes: genetic (e.g. Klinefelter), specific structural sperm defects (e.g. globozoospermia), varicocele, (epididymo)orchitis and cryptorchism exhibiting a 5-fold increased risk for the development of testicular cancer representing the most common cancer among men aged 25-40 years. The main manifestation of impaired spermatogenesis however is an arrest at different developmental stages.
SPERMATOGENESIS occurs within the epithelium of the seminiferous tubules which contain somatic Sertoli cells and germ cells of differing developmental stages. Mitotic active spermatogonia both reproduce themselves for stem cell renewal and produce daughter cells that develop into spermatocytes. Spermatocytes undergo meiosis and give rise to spermatids which then transform into spermatozoa. This complex transformation, called spermiogenesis, includes nuclear condensation, acrosome formation and the development of a flagellum. Although the main developmental processes take place in the testis, the contribution of the epididymis to the maturation of spermatozoa is crucial. Beyond its role of storage and transport, it is during the sperm´s passage through the epididymis that progressive motility and fertilizing ability are attained.
As the testes from infertiliy men contain small areas with qualitatively normal spermatogenesis that allow testicular sperm extraction (TESE) to be carried out, therapeutic testicular biopsies play an important role in the treatment of their infertility. It is this diagnosis that the Clinical Research Unit KFO 181 seeks to improve by applying molecular and cell biology techniques. An outstanding feature of this Clinical Research Unit is the ability to follow up initial findings from animal and in-vitro model systems on cryopreserved and fixed human testicular material.
Testicular biopsies of these men reveal mixed atrophy with seminiferous tubules with qualitatively normal spermatogenesis directly adjacent to tubules with spermatogenic arrest and/or Sertoli-cell-only (SCO) (Figure).