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RESEARCH |
Department of Endocrinology, Dr ALM Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600 113, India, 1 Department of Biochemistry, Central Leather Research Institute, Chennai 600 025, India and 2 Department of Animal Science, Bharathidasan University, Tiruchirappalli 620024, India
Correspondence should be addressed to M M Aruldhas; Email: aruldhasmm{at}yahoo.com
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Abstract |
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
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The epididymis, present only in the amniotes, is formed of a single long convoluted and contorted duct, and plays an important role in post-testicular sperm maturation (Cooper 1998). It is differentiated anatomically, histologically and functionally into a number of segments along its length (Robaire & Hermo 1988). The success of in vivo or in vitro fertilization or intracytoplasmic sperm injection in assisted reproductive technologies, using spermatozoa collected from different segments of the epididymis, depends on the extent of epididymal maturation of sperm (Cooper 1993). There are also reports suggesting the epididymis as a target for certain toxicants (Gray & Kelce 1996, Mann 1997, Hess 1998, Klinefelter 2002). If that is the case, epididymal sperm maturation can be affected, leading to perturbation in the fertility of subjects exposed to such toxicants. Therefore, it would be pertinent to investigate the responses of the epididymis to more of the toxic substances, including environmental chemicals (Hess 1998, Klinefelter 2002).
Male reproductive toxicity of heavy metal pollutants such as cadmium, lead and mercury is well known (Zylber-Haran et al. 1982, Rodamilans et al. 1988, Vachhrajani & Chowdhury 1990). Chromium (Cr) is another occupational heavy metal pollutant to which workers in nearly 50 industries, including chromeplating, stainless steel welding and vulcanizing industries, ordnance factories and tanneries, are exposed (Burrows 1983). Further, emissions and effluents from these workplaces and industries contaminate the environment, which may affect man and animals living in the surrounding areas (Outridge & Scheuhammer 1993). In the living system, Cr (VI) is rapidly converted to Cr (III), which is less toxic. However, recent studies have shown that even Cr (III) can damage DNA (DeFlora et al. 1990, Codd et al. 2001).
Dermatitis, cancer of the lung, nasal ulcers and kidney diseases are the well-known toxic effects of chromium in man (Barceloux 1999). Despite a few reports on rodent models, the male reproductive toxicity of chromium has not been viewed seriously so far. This is mainly due to the failure of a few studies to show any correlation between body chromium and fertility in men who are occupationally exposed to chromium in the welding industries (Bonde 1993). However, a recent study on metal welders suggested that the conclusions of Bonde may not be applicable to those exposed to a high level of welding fumes or other putative hazards (Hjollund et al. 1998). In a recent review, Bonde (2002) has also opined that evidence for the male reproductive toxicity of chromium is very limited.
Experiments in rat models have revealed that i.p. administration of Cr (VI) can result in testicular toxicity, manifested as premature release of germ cells from Sertoli cells, formation of multinucleate spermatids, decreased sperm counts and subnormal androgen secretion (Ernst 1990, Saxena et al. 1990, Ernst & Bonde 1992, Chowdhury & Mitra 1995). We have observed poor semen quality and disruption of spermatogenesis in monkeys (Macaca radiata) exposed to different doses of Cr (VI) through their drinking water for 6 months. This was attributed to the generation of reactive oxygen species in the testis and epididymis (Aruldhas et al. 2000).
In the light of the above background in the literature, it is proposed that occupational or environmental exposure to Cr (VI) might, in addition to affecting the testis, also affect the epididymis. The hypothesis was tested in a non-human primate model, Macaca radiata, subjected to chronic chromium exposure through their drinking water for 180 days. In the present paper, we report the development of two different kinds of microcanals in the epididymal epithelium and the probable mechanisms underlying their development.
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Materials and Methods |
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Experimental design
Adult male bonnet monkeys (Macaca radiata), trapped by the Department of Forest and Wild Life, Government of Tamil Nadu, India, for creating a public nuisance, were procured with permission from the Chief Wildlife Warden, Chennai, India. Animals were kept under quarantine and acclimatized to animal house conditions for 2 months before the experiment. They were kept individually in spacious cages built as per the specifications of CPCSEA (60 x 60 x 80 cm), under ambient temperature (28 ± 2 °C) and light and dark schedules (12 ± 1 h) in a well-ventilated animal quarter. All animals were fed ad libitum with pellet diet for monkeys (Brooke Bond Lipton India Ltd, Calcutta, India), rice cooked with dhal, vegetables such as potato and beetroot and seasonally available fresh fruits such as banana and guava.
Treatment and analysis
The monkeys were divided into four groups, each consisting of three animals. Groups I to III were provided with drinking water containing Cr (VI) (potassium dichromate) at a concentration of 100, 200 and 400 p.p.m. respectively for 180 days. Group IV consisted of control animals, which were provided with chromium-free drinking water. At the end of the experiments, the monkeys were dissected under sodium pentathol anaesthesia (40 mg/kg body weight), and the testicles and epididymides were removed. As the tissues from the same animals were used for spermatological, biochemical, histological and ultrastructural studies, perfusion fixation was not practised. Slices of the testicles and the different segments of the epididymis were immersion fixed in 2.5% glutaraldehyde prepared in cacodylate buffer and post-fixed in 1% osmium tetroxide (Hess & Thurston 1977). Tissues were dehydrated in grades of alcohol and propylene oxide and embedded in thin viscosity resin (Sigma Chemical Company, St Louis, MO, USA). Semithin sections (1 µm thickness) obtained in an ultramicrotome (Leica Microsystems Nussloch GmbH, Nussloch, Germany) were stained in toluidine blue O (TBO) and used for light microscopic observations and histometry of the microcanals. Ultrathin sections were stained in uranyl acetate and lead citrate and observed in a Phillips 201C transmission electron microscope. Image analysis and processing were done using Axiovision Image Analysis software (Carl Zeiss GmbH, Jena, Germany). For histometric measurements of the microcanals, data were used to calculate the respective means and standard deviations.
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Results |
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One kind of microcanal that was predominant consisted of irregular oval or oblong shaped lumina measuring 104 ± 28 µm along the longest axis and 52 ± 11 µm across. The lumen of this type of microcanal contained a few spermatozoa but cell debris was occasionally seen (Fig. 1
). The microcanal was lined by short to tall columnar principal cells (Fig. 2). In all other respects, these principal cells were comparable with the principal cells of an unaffected cauda epididymidis. Although the roof of this kind of microcanal was also lined by principal cells whose nuclei were similar to those in the floor, these cells did not have any contact with the basement membrane, and appeared as floating cells. The lumen of the microcanal had a stellate appearance in view of the dome-shaped luminal ends of the lining principal cells.
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) was rare, narrow and more circular in outline than the earlier one. In transection, they measured 37 ± 4 µm along the longest axis and 28 ± 3 µm along the shortest axis. Although low-power light micrographs suggested that they were lined by principal cells as in the earlier case (Fig. 3a), a careful examination revealed closely applied arcs of cytoplasm staining more intensely with TBO than the surrounding principal cells (Fig. 3b). Although principal cell nuclei were found on the sides and top of such microcanals, they were missing at the base. The nuclei of the cells immediately lining the microcanal were smaller in diameter (about 4–6 µm) than the nuclei of principal cells (8–10 µm). The profile of this microcanal resembled a rosette. Microvilli, longer and more profuse than in the earlier type of microcanal, were seen to extend deep into the lumen, and their abundance was more at the junctional points of the rosette than in the other parts. Invariably, the lumen contained sperm and/or cell debris (Figs 3c and 4).
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), and invariably the cytoplasm of these two cell types differed in electron density (Fig. 5b). The lining cells established tight junctions at the points of contact and produced tall, branching microvilli into the lumen (Figs 5a and 6a). A single cell, different in organization and electron density from the principal cells, contacted the basement membrane on one side and surrounded the basal portion of the microcanal above (Fig. 5). In such an organization, the cell had a stalk contacting the basement membrane and the apical portion extending around a portion of the microcanal-like arms. The cytoplasm of such cells possessed extensive saccular rough endoplasmic reticulum and abundant mitochondria with plicate cristae (Fig. 6b). The Golgi apparatus, which was prominent, closely approximated the nucleus and faced the luminal side of the cell (Fig. 6b). The cytoplasm also contained dense spherical granules that, from the morphology and electron density, could be inferred to be lysosomes (Fig. 6).
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). In the second instance, in the monkeys belonging to the 200 p.p.m. chromium-treated group, although the epithelium appeared pseudostratified, it did not form the obstructing villositis. However, the lumen was fully packed with immature germ cells and macrophages that had phagocytosed spermatozoa and cell debris. The luminal content was thus clearly obstructing the lumen (Fig. 8). Light micrographs of the testis of control and treated monkeys revealed that, in the latter, the seminiferous epithelium was thoroughly disrupted and multinucleate giant cells were generated. Immature germ cells and multinucleate giant cells were released into the lumen (Fig. 9) to arrive at the epididymis (Fig. 8). In the third instance, in the monkeys belonging to 100 p.p.m. chromium-treated group, the epithelium of the cauda epididymidis was pseudostratified, and the lumen contained an occluding density that was formed of neither sperm nor immature germ cells, but nuclei matching those of principal cells (Fig. 10a and b). Degeneration of the principal cells of caput and corpus epididymides of Cr (VI)-treated monkeys was noticed and the nuclei of such cells arrived at the lumen (Fig. 10c) to reach the cauda epididymidis (Fig. 10a and b).
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). The rupture could perhaps have begun at disintegrating principal cells (Fig. 11a–c) and such spermatozoa would have proceeded towards the basement membrane (Fig. 11d), where basal cells were invariably present (Figs 11d and e and 12). However, in spite of such extensive damage of the epithelium, spermatozoa were confined to the epithelium.
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Discussion |
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Ductal obstruction
As discussed above, three different mechanisms of ductal obstruction were observed in the distal cauda epididymidis of chromium-treated monkeys. The first one pertains to hypertrophy of the epithelium and its formation into villosities. To the best of our knowledge such a development has not been reported in any situation, although villous folding of the epithelium has been reported in the corpus epididymidis of orchidectomized goats supplemented with testosterone, and in the cauda epididymidis of reteligated goats (Goyal et al. 1994). The situation in the present case may be due to a hormonal imbalance consequent to chromium treatment, as the epididymis is an androgen-dependent organ (Robaire & Hermo 1988). The arrival of a smaller number of spermatozoa at the cauda epididymidis as a result of disruption in spermatogenesis (Ernst 1990, Saxena et al. 1990, Murthy et al. 1991, Ernst & Bonde 1992, Chowdhury & Mitra 1995) may be another reason. We have found decreased testosterone titre and sperm count in the chromium-treated monkeys of the present study (Aruldhas et al. 2000).
Obstruction due to the arrival of immature germ cells, multinucleate giant germ cells and macrophages, as observed in the present study, is known in a few experimental situations such as carbendazim treatment of rats (Nakai et al. 1993), aflatoxin treatment of mice (Agnes & Akbarsha 2001), phosphamidon treatment of rats (Akbarsha & Sivasamy 1998) and in several cases of vasectomy or ligation of vas deferens (Flickinger et al. 1999). In the above situations, the obstructing mass was invariably granuloma. The arrival of immature germ cells at the epididymal duct in the present case is the consequence of a premature loss of germ cells caused by chromium treatment, which is consistent with two earlier reports on chromium-treated rodents (Ernst 1990, Ernst & Bonde 1992). Detention of sperm in the epididymal duct for more than the usual period of time results in deterioration and attraction of macrophages, which phagocytose dead and/or defective sperm and cleanse them (Turner et al. 2000, Flickinger & Howards 2002).
The third situation of filling the lumen of the duct with cells and debris which are not of testicular origin has been reported in the aflatoxin-treated mouse (Agnes & Akbarsha 2001), in which the debris was degenerating principal cells of the more proximal segments of the epididymis. A similar situation was also observed in the present study.
Development of type 1 microcanal
The first type of microcanal, lined all around by principal cells, appears to provide passage for spermatozoa to bypass the obstructed main duct, thus patenting the microcanal. The development of patenting microcanals has been reported in the occluded efferent ductules of carbendazim-treated rats (Nakai et al. 1993) and in the vas deferens of vasectomized men and experimental animals (Hayashi et al. 1983, Cruickshank et al. 1987, Freund et al. 1989). According to Nakai et al.(1993), microcanals are formed in the ductuli efferentes from the epithelium that has escaped inflammation. During this process, the edges of the proliferated epithelium migrate into the lumen and the sprouting epithelium from different directions meet on top of a canal. In this case, the original duct is partitioned into two or more canals, one or more of which transform into patenting microcanals and the other(s) retaining the occluded mass. The microcanal thus formed is lined by both migrated and native epithelium. Lateral and basal surfaces of the migratory epithelial cells are irregular in outline and without a basal lamina. Nakai et al.(1993) have observed microcanalization in the efferent ductules, whereas in the present study it had occurred in the cauda epididymidis. Patenting microcanals of the epididymis have not been reported elsewhere, to the best of our knowledge, although a kind of re-epithelialization process has been reported in human epididymis (Ball & Mitchinson 1984).
Rupture of epithelium and entry of spermatozoa into the epithelium
Obstruction due to immature germ cells arriving at the distal part of the epididymis and profuse periodic acid Schiff-positive granules released due to degeneration of principal cells at the intermediate zone of the epididymis of mice treated with aflatoxin has been recently reported (Agnes & Akbarsha 2001). Such an obstruction has been shown to result in degenerative changes in the principal cells in all the segments of the epididymis, establishing continuity between the ductal lumen and the principal cells; spermatozoa were seen in such damaged cells even up to or closer to the basement membrane. Although a comparable situation was obtained in the present study, epithelial degeneration in the cauda epididymidis was found in a large scale, providing scope for a more copious entry of spermatozoa into the epithelium. There are a few earlier reports on epididymal rupture, one in men following long periods of vas obstruction (Silber 1979), and the other in the mouse treated with testosterone where there was no ductal obstruction (Itoh et al. 1999). Thus, the present finding has shown the rupture of cauda epididymidal epithelium in monkeys, which were exposed to chromium for a chronic period, due to obstruction in the cauda itself forcing spermatozoa to enter into weaker patches in the epithelium.
The entry of spermatozoa into the epithelium can be viewed from another perspective. Aruldhas et al.(2000) have observed an increased concentration of electrophiles and decreased activities of antioxidant enzymes in the caput and cauda epididymides of the chromium-treated monkeys used in the present study. This could also be a consequence of the ductal obstruction. Thus, the sperm in the cauda epididymidis of chromium-treated monkeys would have been under severe stress, and they tended to escape through weak patches in the epithelium.
Type 2 microcanals as a protective device to prevent extravasations of spermatozoa entering through the weak patches in the epithelium
Spermatozoa can evoke an autoimmune response if they are extravasated (Nashan et al. 1990, Flickinger et al. 1995, 1998, 1999) as seen after vasectomy (McDonald 2000, McGinn et al. 2000), and can result in provocation of an autoimmune response of extravasated sperm granuloma formation. Autoimmune response to sperm antigens is an established fact, and is the basis for infertility in men undergoing vasectomy (Alexander 1975, Alexander & Anderson 1979, Rose & Lucas 1979, Tung & Menge 1985, Flickinger et al. 1986).
Agnes & Akbarsha (2001) proposed that, on entry of spermatozoa into the epithelium through degenerating principal cells, extravasation of spermatozoa is prevented by the underlying basal cell, which develops into a pale vacuolated epithelial cell (PVEC) and encloses such spermatozoa in a lumen within the cell. The type 2 microcanal observed in the present study fulfils this role, as the spermatozoa reached up to the basement membrane through the weaker patches in the epithelium where basal cells are present. The structural organization of the cells lining this kind of microcanal in the monkey epididymis is comparable with that of PVEC in the mouse epididymis, although it forms a single cell in the mouse epididymis. The cauda epididymidal epithelium in the monkey being about three times taller than that of the mouse (Alsum & Hunter 1978), a single basal cell may not be sufficiently adequate to form a structure to enclose the sperm which would extravasate. Therefore, four or five basal cells might have grown around the damaged epithelium and encircle spermatozoa in the lumen. The suggestion that the participating cells are basal cells is based on the observation that they are different in ultrastructural organization from the principal cells and clear cells. Clear cells have been recently reported to be present in the cauda epididymidal epithelium of the monkey (Bomgardner et al. 1999). Further, the principal and clear cells have not so far been reported to transform into any other cell type. The role of basal cells in producing structures which seclude the spermatozoa arriving at the site of epithelial ruptures to prevent their extravasation, and thereby avoiding the generation of antibodies, may be justified in the light of the fact that basal cells consistently express F4/80 and mac-1 antigens. Basal cells are possibly tissue-fixed macrophages, and provide immune defence against sperm antigens (Seiler et al. 1998, 2000, Hoischbach & Cooper 2002). However, since our inference is based purely on histological evidence, the possibility that the cells lining the type 2 microcanals are modified principal cells or even yet another cell type hitherto unknown cannot be ruled out at present. Immunocytochemical tests for specific markers for the various cell types in the epididymal epithelium need to be carried out to identity the cell type lining this microcanal. Until confirmation, the lining cells may be designated as microcanal boundary cells.
Relationship between dose and response
The histopathological changes in the testis and epididymis, and also the incidence of microcanalization in the cauda epididymidal epithelium were dependent on the concentration of chromium in the drinking water. Although the amount of chromium in the experimental animals was not quantified, the impact was most acute in the animals exposed to water containing 400 p.p.m. chromium, followed by the groups exposed to 200 p.p.m. and 100 p.p.m.
Thus, the present study has revealed that the epididymis could be a target organ for chromium toxicity, and also be a versatile organ capable of overcoming adverse situations by diverse devices.
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Footnotes |
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Received 20 March 2003
First decision 25 June 2003
Accepted 31 March 2004
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References |
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Agnes VF & Akbarsha MA 2001 Pale vacuolated epithelial cell in epididymis of aflatoxin-treated mice. Reproduction 122 629–641.[Abstract]
Akbarsha MA & Sivasamy P 1998 Male reproductive toxicity of phosphamidon: histopathological changes in epididymis. Indian Journal of Experimental Biology 36 34–38.[Medline]
Alexander NJ 1975 Immunologic and morphologic effects of vasectomy in the rhesus monkey. Federation Proceedings 34 1692–1697.[ISI][Medline]
Alexander NJ & Anderson DJ 1979 Vasectomy – consequences of autoimmunity to sperm antigens. Fertility and Sterility 32 253–273.[ISI][Medline]
Alsum DJ & Hunter AG 1978 Regional histology and histochemistry of the ductus epididymis in the rhesus monkey (Macaca mullata). Biology of Reproduction 19 1063–1069.[Abstract]
Aruldhas MM, Govindarajulu P & Chandra Hasan G 2000 Effect of chronic chromium exposure on sperm maturation and male fertility. In Final Technical Report of major research project sponsored by Council of Scientific and Industrial Research, Government of India, New Delhi (no. 60(0022)/EMR II/97).
Ball RY & Mitchinson MJ 1984 Obstructive lesions of the genital tract in men. Journal of Reproduction and Fertility 70 667–673.[Abstract]
Barceloux D 1999 Chromium. Journal of Toxicology and Clinical Toxicology 37 173–194.[CrossRef][ISI][Medline]
Bomgardner D, Wehrenberg U & Rune GM 1999 TGF-beta could be involved in paracrine actions in the epididymis of marmoset monkeys (Callithrix jacchus). Journal of Andrology 20 375–383.
Bonde JP 1993 The risk of male sub fertility attributable to welding of metals. International Journal of Andrology 1 1–29.
Bonde JP 2002 Occupational risk to male reproduction. Giornale Italiano di Medicina del Lavoro ed Ergonomia 24 112–117.[Medline]
Burrows D 1983 Chromium Metabolism and Toxicology. Florida: CRC Press.
Cheek AO & McLachlan JA 1998 Environmental hormones and the male reproductive system. Journal of Andrology 19 5–10.
Chowdhury AR & Mitra C 1995 Spermatogenic and steroidogenic impairment after chromium treatment in rats. Indian Journal of Experimental Biology 33 480–484.[Medline]
Codd R, Dillon CT, Levina A & Lay PA 2001 Studies on the genotoxicity of chromium from the test tube to the cell. Coordination Chemistry Reviews 216–217 537–582.[CrossRef]
Cooper TG 1993 The human epididymis – is it necessary? International Journal of Andrology 16 245–250.[ISI][Medline]
Cooper TG 1998 Epididymis. In Encyclopedia of Reproduction, vol 2, pp 1–17. Eds E Knobil & JD Neill. New York: Academic Press.
Cruickshank B, Eidus L & Barkin M 1987 Regeneration of vas deferens after vasectomy. Urology 30 137–142.[CrossRef][ISI][Medline]
DeFlora S, Bagnasco M, Serra D & Zanacchi P 1990 Genotoxicity of chromium compounds: a review. Mutation Research 238 99–172.[ISI][Medline]
Ernst E 1990 Testicular toxicity following short-term exposure to tri-and hexavalent chromium: an experimental study in the rat. Toxicology Letters 51 269–275.[CrossRef][ISI][Medline]
Ernst E & Bonde JP 1992 Sex and epididymal sperm parameters in rat following subchronic treatment with hexavalent chromium. Human and Environmental Toxicology 11 255–258.
Flickinger CJ & Howards SS 2002 Consequences of obstruction on the epididymis. In The Epididymis: From Molecules to Clinical Practice, pp 503–521. Eds B Robaire & BJ Hinton. New York: Kluwer Academic/Plenum Publishers.
Flickinger CJ, Yarbro ES, Howards SS, Herr JC, Caloras D, Gallien TN & Spell DR 1986 The incidence of spermatic granulomas and their relation to testis weight after vasectomy and vasovasostomy in Lewis rats. Journal of Andrology 7 285–291.
Flickinger CJ, Howards SS & Herr JC 1995 Effects of vasectomy on the epididymis. Microscopy Research and Technique 30 82–100.[CrossRef][ISI][Medline]
Flickinger CJ, Baran ML, Howards SS & Herr JC 1998 Epididymal obstruction during development results in antisperm auto antibodies at puberty in rats. Journal of Andrology 19 136–144.
Flickinger CJ, Bush LA, Williams MV, Naaby-Hansen S, Howards SS & Herr JC 1999 Post-obstruction rat sperm autoantigens identified by two-dimensional gel electrophoresis and western blotting. Journal of Reproductive Immunology 43 35–53.[CrossRef][ISI][Medline]
Freund MJ, Weidmann JE, Goldstein M, Marmar J, Santulli R & Oliveira N 1989 Microrecanalization after vasectomy in man. Journal of Andrology 10 120–132.
Goyal HO, Hutto V & Maloney MA 1994 Effects of androgen deprivation in the goat epididymis. Acta Anatomica 150 127–135.[ISI][Medline]
Gray LE Jr & Kelce WR 1996 Latent effects of pesticides and toxic substances on sexual differentiation of rodents. Toxicology and Industrial Health 12 515–531.[ISI][Medline]
Hayashi H, Cedenho AP & Sadi A 1983 A The mechanism of spontaneous recanalization of human vasectomized ductus deferens. Fertility and Sterility 40 269–270.[ISI][Medline]
Hess RA 1998 Effects of environmental toxicants on the efferent ducts, epididymis and fertility. Journal of Reproduction and Fertility Supplement 53 247–259.
Hess RA & Thurston RJ 1977 Ultrastructure of epithelial cells in the epididymal region of the turkey (Meleagris gallopavo). Journal of Anatomy 124 765–778.[ISI][Medline]
Hjollund NH, Bonde JP, Jensen TK, Ernst E, Henriksen TB, Kolstad HA, Giwercman A, Skakkebaek NE & Olsen J 1998 Semen quality and sex hormones with reference to metal welding. Reproductive Toxicology 12 91–95.[CrossRef][ISI][Medline]
Hoischbach C & Cooper TG 2002 A possible extratubular origin of epididymal basal cells in mice. Reproduction 123 517–525.[Abstract]
Itoh M, Miyamoto K, Satriotomo I & Takeuchi Y 1999 Spermatic granulomata are experimentally induced in epididymides of mice receiving high-dose testosterone implants: a light-microscopical study. Journal of Andrology 20 551–558.
Klinefelter GR 2002 Actions of toxicants on the structure and function of the epididymis. In The Epididymis: From Molecules to Clinical Practice, pp 353–360. Eds B Robaire & BJ Hinton. New York: Kluwer Academic/Plenum Publishers.
Mann PC 1997 Selected lesions of dioxin in laboratory rodents. Toxicologic Pathology 25 72–79.[ISI][Medline]
McDonald SW 2000 Cellular responses to vasectomy. International Review of Cytology 199 295–339.[CrossRef][ISI][Medline]
McGinn JS, Sim I, Bennett NK & McDonald SW 2000 Observations on multiple sperm granulomas in the rat epididymis following vasectomy. Clinical Anatomy 13 185–194.[CrossRef][ISI][Medline]
Murthy RC, Saxena DK, Gupta SK & Chandra SV 1991 Ultrastructural observations in testicular tissue of chromium-treated rat. Reproductive Toxicology 5 443–447.[CrossRef][ISI][Medline]
Nakai M, Moore BJ & Hess RA 1993 Epithelial reorganization and irregular growth following carbendazim-induced injury of the efferent ductules of the rat testis. Anatomical Records 235 51–60.[CrossRef]
Nashan D, Cooper TG, Knuth UA, Schubeus P, Sorg C & Nieschlag E 1990 Presence and distribution of leucocyte subsets in the murine epididymis after vasectomy. International Journal of Andrology 13 39–49.[ISI][Medline]
Outridge PM & Scheuhammer AM 1993 Bioaccumulation and toxicology of chromium: implications for wildlife. Reviews of Environmental Contamination and Toxicology 130 31–77.[ISI][Medline]
Robaire B & Hermo L 1988 Efferent ducts, epididymis, and vas deferens: structure, function, and their regulation. In The Physiology of Reproduction, pp 999–1080. Eds E Knobil & J Neill. New York: Raven Press.
Rodamilans M, Osaba MJ, To-Figueras J, Rivera-Fillat F, Marques JM, Pérez P & Corbella J 1988 Lead toxicity on endocrine testicular function in an occupationally exposed pollution. Human and Experimental Toxicology 7 125–128.
Rose NR & Lucas PL 1979 Immunologic consequences of vasectomy: II. Two-year summary of a prospective study. In Vasectomy: Immunologic and Pathophysiologic Effects in Animals and Man, pp 533–573. Eds IH Lepow & R Crozier. New York: Academic Press.
Saxena DK, Murthy RC, Lal B, Srivastava RS & Chandra SV 1990 Effect of hexavalent chromium on testicular maturation in the rat. Reproductive Toxicology 4 223–228.[CrossRef][ISI][Medline]
Seiler P, Wenzel I, Wagenfeld A, Yeung CH, Nieschlag E & Cooper TG 1998 The appearance of basal cells in the developing murine epididymis and their temporal expression of macrophage antigens. International Journal of Andrology 21 217–226.[CrossRef][ISI][Medline]
Seiler P, Cooper TG & Nieschlag E 2000 Sperm number and condition affect the number of basal cells and their expression of macrophage antigen in the murine epididymis. International Journal of Andrology 23 65–76.[CrossRef][ISI][Medline]
Silber S 1979 Epididymal extravasation following vasectomy as a cause for failure of vasectomy reversal. Fertility and Sterility 31 309–315.[ISI][Medline]
Tung KSK & Menge AC 1985 Sperm and testicular autoimmunity. In The Automimmune Disease, pp 537–590. Eds. NR Rose & IR Mackay. New York: Academic Press.
Turner TT, Riley TA, Vagnetti M, Flickinger CJ, Caldwell JA & Hunt DF 2000 Post-vasectomy alterations in protein synthesis and secretion in the rat caput epididymidis are not repaired after vasovasostomy. Journal of Andrology 21 276–290.[Abstract]
Vachhrajani KD & Chowdhury AR 1990 Distribution of mercury and evaluation of testicular steroidogenesis in mercuric chloride and methylmercury administered rats. Indian Journal of Experimental Biology 28 746–751.[ISI][Medline]
Zylber-Haran EA, Gershman H, Rosenmann E & Spitz IM 1982 Gonadotrophin, testosterone and prolactin interrelationships in cadmium-treated rats. Journal of Endocrinology 92 123–130.[Abstract]
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