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ACTIONS OF TOXICANTS ON THE STRUCTURE AND FUNCTION OF THE EPIDIDYMIS
Citation:
Klinefelter, G R. ACTIONS OF TOXICANTS ON THE STRUCTURE AND FUNCTION OF THE EPIDIDYMIS. Chapter 20, B Robaire & B Hinton (ed.), The Epididymis: From Molecules to Clinical Practice. Plenum Press, New York, NY, , 353-369, (2002).
Description:
Given the public's concern regarding a putative decline male reproductive health, toxicology of the epididymis will become an area of greater research. Environmental chemicals and pharmaceutical agents can alter the structure and/or function of the epididymis via either direct or indirect mechanisms. Many exposures result in epididymis-specific alterations in epididymal sperm transit, and it seems reasonable to suspect that the fertility of epididymal sperm might decline from either an abbreviated opportunity for maturation within the epididymal duct associated with agents that accelerate transit, or from decreased numbers of ejaculated sperm associated with agents that impede contractility of the distal regions of the epdidymis and vas deferens. While the role of the human epididymis in the acquisition of fertility has been challenged, it is clear that sperm recovered from more distal segments of the epididymis have greater fertilizing potential than those in more proximal segments. Thus, a reduced opportunity to undergo epididymal influences pivotal to maximum fertility could have significant implications.
Despite the diversity of the chemicals which perturb the epididymis, there are numerous common manifestations. First, epididymal toxicants frequently produce epididymis-specific alterations in epididymal sperm numbers. Second, we and others have observed a disappearance of clear cells in the proximal cauda epididymis. Third, specific secretory and sperm-associated proteins appear to be sensitive to chemical insult. Secretory proteins such as clusterin a and b and proteins B/C (RABP 1 and 2) are compromised as is the sperm protein SP22. Fourth, when expression of SP22 is diminished, so is the fertility of cauda epididymal sperm.
Given that many environmental chemical are being shown to disrupt the endocrine axis, that differentiation of the Wolffian ducts depends on both mullerian inhibiting substance and testosterone, and that the postnatal development and maintenance of the epididymis is regulated by androgens, it seems inevitable that increasing attention must be paid to the differentiation and development of the epididymis following pre- and/or perinatal exposures to endocrine disruptive chemicals. Indeed the increasing incidence of partial or complete agenesis of the epididymis, ventral prostate, and seminal vesicles in adult male offsring exposed to antiandrogenic chemicals during critical periods of reproductive development may ultimately be linked to a decline in human sperm quality. At a minimum, proteomic-genomic based assessments of epididymal development following developmental insults will most certainly lead to new concepts in epididymal biology.