Human Spermatogenesis: Insights From the Clinical Care of Men With Infertility

Human spermatogenesis is a qualitatively and quantitatively different process than that observed for most other mammals. In contrast with most other mammals, human spermatogenesis is characterized by reduced quantitative production and more abnormal sperm morphology. Until recently, direct evaluation and observations of human sperm production has been limited and the majority of scientific knowledge regarding spermatogenesis was derived from rodent models of study. Unique opportunities to observe human spermatogenesis have occurred as a consequence of the treatment of severe male infertility. These patients have sperm production so limited that no sperm reach the ejaculate so their fertility treatment involves surgical sperm retrieval from the testis, coupled with use of those sperm with advanced assisted reproductive techniques. Treatment of men with severe male infertility has enhanced identification of new genetic abnormalities that may cause this condition, since they now seek medical care. Three key novel concepts have resulted: (a) spermatogenesis is spatially heterogeneous in the human male, especially when sperm production is compromised, (b) genetic abnormalities are common in men with severe male infertility, particularly in men with diffuse maturation arrest and (c) rodent studies may not be an ideal model for understanding human male infertility. Scientific understanding of human spermatogenesis has been enhanced by these clinical observations.