Biologic Markers in Reproductive Toxicology (1989) / Chapter Skim
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5. Biologic Markers of Epididymal Structure and Function
5. Biologic Markers of Epididymal Structure and Function
Pages 63-76
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From page 63... ...
Several reviews on various facets of epididymal structure and function have appeared in the past 15 years (Hamilton, 1972; Bedford, 1975; Hamilton, 1975; Neaves, 1975; Orgebin-Crist et al., 1975; Turner, 1979; Hinton, 1980; Courot, 1981; Orgebin-Crist, 1981; Brooks, 1982; Glover, 1982; Howards, 1983; Orgebin-Crist, 1984; Cooper, 1986; Amann, 1987; Robaire and Hermo,1987~. To monitor whether a toxicant has compromised male fertility, it is essential to determine not only whether the normal physiologic functions of the epididymis are still being performed, but also whether the toxicant has so altered the spermatozoa while they were in the epididymis that they cannot fertilize eggs or can fertilize eggs but produce only nonviable or abnormal offspring.
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From page 64... ...
It would be surprising if they could not; but such drugs affect an array of other systems, so their effects on the epididymis might be masked. Although the exact epididymal effects of modulating neuronal activity would be of interest, measurements of neuronally mediated epididymal contractility and of the factors that regulate it will probably not become selective markers.
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From page 65... ...
CHANGES IN MATURING SPERMATOZOA A number of morphologic and biochemical changes reported to occur in spermatozoa during transit through the epididymis and vas deferens have been reviewed extensively (Bedford, 1975; Bedford, 1979; Olson and Orgebin-Crist, 1982; Eddy et al., 1985; Cooper, 1986; Robaire and Hermo, 1987~. Structural Changes The most consistent morphologic change that takes place in spermatozoa during ductal transit is the migration of the cytoplasmic droplet from the neck region of the flagellum to the end of the midpiece of the sperm (mitochondrial sheath)
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From page 66... ...
If chemicals can affect spermatozoa by preventing the proper chromatin condensation that takes place while spermatozoa are in the epididymis, then measuring such rates might provide a simple and useful biologic marker. The anionic charge on spermatozoa increases as they reach the cauda epididymis (Bedford, 1975; Toowicharanont and Chulavatnatol, 1983~; the increase is probably acquired during passage through the corpus epididymis (Fain-Maurel et al., 1983~.
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From page 67... ...
The rate of luminal flow in different segments of the rat epididymis decreases from 210 mm/in in the initial segment to 32 mm/in in the distal caput and 12 mm/in in the cauda epididymis and vas deferens(Jaakkola, 1983~. The mechanisms responsible for driving the luminal contents through the efferent ducts and epididymis include hydrostatic pressure (Johnson and Howards, 1976; Pholpramool et al., 1984)
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From page 68... ...
Studies are needed to establish which drugs can modulate such transport and whether the effects will alter the ability of spermatozoa to fertilize eggs or to produce normal, viable offspring. Acquisition of Fertilizing Ability In mammals, spermatozoa leaving the testis do not have the ability to fertilize eggs, whereas those in the cauda epididymis have acquired this function.
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From page 69... ...
From the efferent ducts all the way through to the vas deferens, numerous changes take place in the makeup of this complex of substances. The only available means of monitoring changes in the composition of the luminal fluid, without removing or irreversibly damaging the tissue, is analysis of the epididymal contribution to semen.
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From page 70... ...
and Turner (1979) demonstrated not only that the disk gel electrophoretic patterns of proteins of different segments of the epididymis and vas deferens differed from those of serum or rete testis fluid, but also that they differed from each other-i.e., there were gradual changes in electrophoretic pattern from the caput to the corpus epididymis and vas deferent.
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From page 71... ...
. There were marked changes in the proportion of various cell types from the initial segment of the caput to the cauda epididymis and changes in the relative cell surface area of a particular cell type in selected segments of the epididymis at specified times after initiation of treatment.
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From page 72... ...
There is now morphologic evidence, especially for the vas deferens, that spermiophagy does occur in a number of species under normal conditions or after mechanical or chemical manipulation. Such a process might involve the epithelial cells that line the duct system or the presence of luminal macrophages.
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From page 73... ...
However, it has become apparent that many other regulatory molecules play specialized roles in maintaining normal epididymal function. The factors that regulate epididymal function-i.e., those for which there are specific binding proteins-do not reach the epididymis only through the circulation (endocrine)
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From page 74... ...
Although mouse epididymis revealed differences of limited value (it does not specifically in distribution of grains in different reflect epididymal activity) , it is a cell types, as well as in different seg useful gross indicator.
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From page 75... ...
It can be substituted for by retinoic acid in most tissues; known exceptions are the retina, the testis, and the epididymis. Selective binding proteins for both retinal and retinoic acid have been identified in most male reproductive tissues (Porter et al., 1985~.
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From page 76... ...
For some compounds, such as dibromochloropropane (DBCP) , it has clearly been shown that there is an effect on the epididymis, e.g., on epididymal weight or sperm reserves (Amann and Berndtson, 1986~; but it is still not clear whether the deleterious effects of this drug, and others like it, on reproductive outcome are directly linked to their action on the epididymis or epididymal spermatozoa.
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