Spermatozoa leaving the testis and entering the long convoluted tubule known as the epididymis are non-functional gametes. It is only during transit through the epididymis that spermatozoa undergo maturation and acquire progressive motility and the ability to fertilize ova. Because spermatozoa are, for the most part, synthetically inactive, maturation involves the interaction of spermatozoa with proteins that are synthesized and secreted in a region-dependent manner from the epididymal epithelium. Despite considerable effort, the molecular and biochemical events that are integral for epididymal sperm maturation are unknown.
The importance of understanding epididymal function and sperm maturation is emphasized by the fact that up to 40% of infertile men exhibit idiopathic infertility that may reflect sperm maturational disorders. Unfortunately, owing to the lack of alternative therapies, these patients and their partners require assisted reproductive techniques (ART) such as intracytoplasmic sperm injection (ICSI), which utilizes spermatozoa independent of maturational status, to achieve a pregnancy. Although effective, because natural selection processes that prevent suboptimal spermatozoa from fertilizing ova are bypassed, there can be increased risks of genetic abnormalities being transmitted to the offspring (Cox et al., 2002
; Merlob et al., 2005
; Georgiou et al., 2006
; Fedder et al., 2007
; Sanchez-Albisua et al., 2007
). If the mechanisms of sperm maturation were established, it is possible that sperm could be matured in vitro
providing an alternative therapy to current reproductive technologies.
The significance of the lack of understanding regarding the functional role of the epididymis in sperm maturation is also underscored by the lack of contraceptives for men. Although much work has been put into developing hormonal methods that interfere with sperm production in the testis, these approaches have been hampered by cumbersome regimes, extended times before efficacy is achieved, and possible side effects of the administered hormones. Interest has shifted to include identifying epididymal molecules that could serve as targets for non- steroidal-based male contraceptives with the idea that sperm production would occur normally but the spermatozoa would be non-functional. Clearly, if we are to improve human health by developing new and better ways to improve as well as prevent fertility, further research into the epididymis is needed.
The purpose of this review is to provide a general background of the epididymis followed by a brief overview of recent progress in the field including advances in our understanding of the epididymal epithelium and its regulation, composition and function of the luminal fluid, as well as changes occurring in spermatozoa during epididymal transit. Because of the limited availability of epididymal tissue from healthy men of reproductive age, the lack of appropriate in vitro models, and the constraint to manipulate the human epididymis experimentally, the majority of these studies have been carried out in rodent models. However, as discussed below, genomic and proteomic analyses of the human epididymis have revealed valuable new information which lends support to the view that, although there may be species differences with regard to where in the epididymis spermatozoa acquire their functions, the human epididymis does serve a role in the functional maturation of spermatozoa.