Recent biochemical approaches to post-testicular, epididymal contraception

Abstract

Results from recent animal models with implications for putative human male contraceptives acting on the epididymis are reviewed. Inducing sterility by enhancing sperm transport through the epididymis has not been achieved. The induction of infertility in males of several species is easier to achieve by direct actions of drugs on sperm function (e.g. inhibition of sperm-specific isoenzymes of the glycolytic pathway by chloro-compounds) than by indirectly reducing amounts of epididymal secretions normally present in high concentration (e.g. alpha-glucosidase, L-carnitine). The former show promise for the clinic since human spermatozoa are susceptible to inhibition. On the other hand, the infertile male mice of the c-ros knock-out model demonstrate the influence of even a small region of the epididymis on fertility, so that targeting the as yet unknown epididymal factors presumably secreted in limiting amounts by this epididymal segment, is a new lead for a contraceptive. Targeting a specific sperm protein acquired in the testis, but depleted in the epididymis by toxicants that induce rapid infertility, may also lead to the discovery of new contraceptives, but these will require developing new means of organ-specific delivery of contraceptive drugs.

Sperm characteristics and ultrastructure of testes of rats after long-term treatment with the methanol subfraction of Carica papaya seeds

“…The results of this investigation show that longterm treatment with MSF for a period up to one year is safe and effective in completely inhibiting sperm motil- It is likely that any contraceptive agent that affects sperm motility would influence spermatozoa indirectly through disruption of epididymal epithelial cell function or act directly on the spermatozoa by affecting their enzymes [31]. In this investigation, although the increase in abnormal sperm count and total inhibition of sperm motility suggest that MSF's target is within the internal milieu of the epididymis, the lack of significant alterations in the epididymal epithelium (unpublished observations) and the unaltered level of epididymal markers (sialic acid, L-carnitine and neutral α-glucosidase) in the cauda epididymis indicate that it is less likely that MSF affects the sperm motility by altering the epididymis itself.…”

Identification of novel immunodominant epididymal sperm proteins using combinatorial approach

“…However, targeting these testicular proteins will not only affect sperm production, but is also likely to lead to disruption of endocrine functions, loss of libido and autoimmune orchitis, which will not be reversible (Jones 1994, DePaolo et al 2000. On the other hand, targeting epididymal sperm maturation events will not impede spermatogenesis and related testicular endocrine function and will provide early onset of infertility with rapid reversal (Cooper & Yeung 1999, Khole 2003.…”

Systematic Mapping and Functional Analysis of a Family of Human Epididymal Secretory Sperm-Located Proteins

“…Dacheux et al (19) performed two-dimensional gel analyses to characterize the human epididymal secretome and epididymosomes have been shown to transfer human epididymal proteins to spermatozoa (20). Although the posttesticular approach offers rapid, effective, and reversible contraception, it requires interference with specific epididymal secretions (21,22), but few such targetable secretions are known. The application of global cloning technology has defined the epididymal transcriptome of a fertile young man (23), which included transcripts found by gene chip arrays from organ donors (24,25) and those in an epididymal cDNA library from elderly prostatic cancer patients (18).…”