Recognising normal spermatogenesis in the testis

In the male animal, recognising the different cellular associations that make up the spermatogenic cycle within seminiferous tubules is essential to be able to identify when cell populations are missing or, in the case of spermatid retention, when they are inappropriately present. An additional challenge in the male animal is the problem of recognising immaturity and distinguishing it from degenerative conditions. This is a particular problem in the dog and non-human primate. Spermatogenesis staging is aided by the use of the correct fixative to preserve the testes (Latendresse et al 2002; Lanning et al 2002).

Spermatogenesis is essentially the same in all mammalian species. It consists of continuous division and maturation of precursor stem cells (spermatogonia), which then enter meiosis (spermatocytes) where they undergo DNA replication and reduction division to form the haploid germ cells (spermatids). These cells undergo a complex morphogenesis, changing from normal appearing cells (round spermatids) to thin whip-like cells (elongating spermatids) that possess a head, body and tail. The mature spermatid is released from the seminiferous epithelium (spermiation) and transported in seminiferous tubule fluid to the collecting reservoir of the rete testis and on into the epididymis via the efferent ducts. The overall process is the same between species, but the detailed characteristics of the different cell types, the kinetics of the process, and the regulatory pathways vary slightly.

The different types of germ cell (spermatogonia, spermatocytes and spermatids) are arranged in a very regular, layered pattern within the seminiferous tubules (Figs 9.1, 9.2). They are supported both structurally and metabolically by the somatic Sertoli cell, which entirely surrounds each germ cell with cytoplasmic processes not readily visible by light microscopy. The true extent of the Sertoli cell becomes more apparent when germ cells are lost from the tubule, leaving only Sertoli cells lining the tubules (Fig. 9.4).

FIGURE 9.1 Rat seminiferous tubule stage V. Tubules in the first half of the cycle (stages I–VIII) contain four layers of germ cells. There are two generations of spermatids (round and elongating spermatids) and only one generation of spermatocytes (pachytene spermatocytes). There is a basal layer of spermatogonia interspersed by Sertoli cell nuclei. ×200.

FIGURE 9.2 Rat seminiferous tubule stage XII. Tubules in the second half of the cycle (stages IX–XIV) also contain four layers of germ cells. There is only one generation of spermatids (elongating spermatids) but there are two generations of spermatocytes (pachytene and prepachytene). There is also a layer of spermatogonia interspersed by Sertoli cell nuclei. ×200.

The germ cells proceed through spermatogenesis in a highly controlled manner, and in any given tubule there are always four generations of germ cells developing in complete synchrony with one another. This gives rise to the concept of stages of the spermatogenic cycle, where each stage can be identified by the precise morphological characteristics of the individual germ cells from the four synchronously developing generations. The detailed description of the cell associations is beyond the scope of this chapter but is comprehensively covered in a number of reviews (Creasy 1997; Creasy & Foster 2002; Russell et al 1990). It is important that the toxicological pathologist be familiar with the concept of the spermatogenic cycle and the different appearances of tubules, at least at the beginning, middle and end of the cycle (Figs 9.1, 9.2) (Foley 2001).

Immaturity, peripuberty, maturity

Rats start releasing sperm from the testis at about six to seven weeks of age, but sperm output does not reach its full potential until about 10–11 weeks of age (for review see Marty et al 2003). The first cycle of spermatogenesis is relatively inefficient, with reduced numbers of maturation-phase spermatids and numerous degenerating germ cells (multinucleate and apoptotic cells) in the seminiferous tubules. The cauda epididymis is only partially expanded and contains variable numbers of sperm as well as cell debris and degenerating sloughed germ cells from the testes (Fig. 9.3a & b). Not all rats will mature at the same rate, and so the appearance can easily be mistaken for testicular toxicity, especially if the test-article-treated animals are slightly less sexually mature due to decreased food intake or decreased body weight.

FIGURE 9.3a Epididymis from a peripubertal eight-week-old rat. The initial segment and caput epididymis are expanded and filled with sperm. ×100.

FIGURE 9.3b Epididymis from a peripubertal eight-week-old rat. The ducts of the distal corpus and cauda epididymis are still contracted and contain few sperm and cell debris. ×40.

Puberty occurs earlier in the mouse, with sperm being present in the epididymis at approximately five weeks of age. As with the rat, degenerating germ cells and low epididymal sperm numbers accompanied by cell debris will be present until spermatogenesis reaches full efficiency at around eight to nine weeks of age.

Congenital or developmental lesions

Absence or incomplete development of the testis (aplasia or hypoplasia) is occasionally seen but is relatively uncommon. Hypoplasia is characterized by a small testis containing reduced numbers of seminiferous tubules. Cryptorchidism, caused by delayed descent of the testis into the scrotal sac, is occasionally seen and results in tubular degeneration and atrophy. This is often difficult to identify at necropsy because rodents can readily retract the testes into the abdominal cavity. Histologically, the cryptorchid testis displays seminiferous tubular atrophy and the tubules are lined solely by Sertoli cells with few spermatogonia.

Lesions seen in young animals: testes

In general, the incidence of background degenerative findings in rodent testes is low, making them a very sensitive species for detecting spermatogenic abnormalities.

Tubular degeneration/atrophy

Occasional tubules (five tubular profiles/testis) with partial or complete depletion of germ cells is a common finding in young adult rats (Fig. 9.4). Tubuli recti, which are the transitional tubules that connect the seminiferous tubules with the rete testis, should not be mistaken for atrophic tubules. Tubuli recti are generally seen immediately adjacent to the main rete testis lumen that is situated at the cranial pole of the testis (Fig. 9.5). The tubuli may also be present in a more lateral subcapsular position, because fingerlike extensions of the rete radiate out from the main sac-like structure.

FIGURE 9.4 Occasional (1–5) atrophic tubules, lined only by Sertoli cells, are commonly seen as a background finding in rat testes. The finding probably represents a loss of germ cells from a short segment of one convoluted seminiferous tubule. ×100.

FIGURE 9.5 Rete testis (rat) lined by cuboidal epithelium with a transitional tubule (tubulus rectus) emptying into it. It is common to see tubules lined only by Sertoli cells (*) close to the rete testis. These are normal profiles of the tubuli recti and should not be mistaken for atrophic tubules. They can often be seen in a subcapsular position somewhat distant from the visible rete because the finger-like projections of the rete testis radiate some distance from the main sac. ×100.

More extensive tubular atrophy, often involving complete loss of all germ cells from all tubules in one or both testes, can sometimes be seen as a background finding in young adult rats (Fig. 9.6a). If the atrophy has been present for more than a few weeks the corresponding epididymis will probably be depleted of sperm and/or germ cells. This can be a useful indication of whether the atrophy was pre-existing, prior to study start, and therefore a background change. Moderate to severe tubular atrophy is often accompanied by increased interstitial fluid (sometimes termed edema) (Fig. 9.6b). Care should be taken when using this diagnosis because fluid accumulation can occur as a fixation artefact, particularly in Bouins-fixed testes (Fig. 9.6b).

FIGURE 9.6a Diffuse tubular atrophy in the rat. Seminiferous tubules lined only by Sertoli cells with all germ cells missing. This can often be seen as a unilateral or bilateral lesion and may be present in young rats and mice. The tubules may have a dilated tubular lumen and be surrounded by interstitial edema. ×100.

FIGURE 9.6b Diffuse tubular atrophy in the rat. The tubules may be contracted with luminal closure (b). This can also be seen as an end-stage, chemically induced lesion (unilateral or bilateral) and so it is important to know the historical background incidence of this finding in the appropriate strain of mouse or rat. ×100.

Other findings that can occasionally be seen include tubular dilatation (unilateral or bilateral) (Fig. 9.7) which may be associated with a dilated rete. Tubular degeneration characterized by varying numbers of degenerating germ cells, including multinucleate giant cells and/or disorganisation of germ cell layers, is sometimes seen as a bilateral background finding (Fig. 9.8).

FIGURE 9.7 Unilateral or bilateral tubular luminal dilatation is occasionally seen in young adult rats. The affected testis or testes are enlarged and generally show increased weight. The lesion may be associated with a dilated rete and likely reflects fluid build-up due to obstruction of the efferent ducts. The lesion generally progresses rapidly to complete tubular atrophy (as in FIGURE 9.6a) due to pressure atrophy, but the tubular lumina often remain dilated. ×100.

FIGURE 9.8 Tubular degeneration (rat) can be seen as an incidental background finding in young rats and mice. It is generally bilateral, and varying numbers of germ cells may show degeneration. The germ cells may form multinucleate or syncytial bodies due to coalescence of germ cells that are normally joined by cytoplasmic bridges. Round spermatids often develop chromatin margination of their nuclei as they degenerate. The degenerate cells are either sloughed into the lumen or phagocytozed by the Sertoli cells. As more cells die, the regular layering of the germ cell layers is lost. ×200.

Abnormal residual bodies (Fig. 9.9) are most commonly seen in the mouse and are characterized by the presence of abnormally large and dense residual bodies that are usually located on the luminal surface of the germinal epithelium in tubules at various stages of the spermatogenic cycle. In contrast, normal residual bodies are much smaller and should only be present at the luminal surface of stage VIII–IX tubules, following which they rapidly descend to the basal region of stage X–XI tubules where they are phagocytosed. Abnormal residual bodies are often seen in tubules in other stages of the cycle.

FIGURE 9.9 Mice testes occasionally contain abnormal-appearing residual bodies (arrowed) as a background lesion. They are larger than normal residual bodies and often occur in tubular stages not normally associated with residual body formation. They can also be increased as a chemically-induced lesion. ×200.

Lesions seen in young animals: epididymides

In the rat and mouse epididymis, sperm is normally present and abundant from the initial segment through to the cauda. In the adult rat, there are generally negligible numbers of sloughed germ cells mixed in with the sperm and so the presence of sloughed cells or debris in the epididymis (particularly in the head) is a very sensitive indicator of testicular injury. Sloughed germ cells are slightly more frequent in the mouse. Spermatogenic disturbances in the testes will generally be reflected by decreased sperm and cell debris in the epididymis.

Sperm granulomas are one of the most common changes seen in young rat epididymides. They may be unilateral or bilateral and can occur anywhere in the epididymis, but are more commonly noted in the cauda (Fig. 9.10). Occasional lymphoid aggregates in the interstitium of the epididymis are a common finding, but are generally few in number.

FIGURE 9.10 Epididymal sperm granuloma is a common background finding in young adult rats. The lesion represents a granulomatous response to sperm (which are antigenically foreign) that have ruptured through the epididymal epithelial lining. Sperm granulomas are more common in the cauda than the caput epididymis. ×100.

Cribriform change, characterized by intra-epithelial microcysts, is a common finding at the junction of the corpus/cauda (Fig. 9.11).

FIGURE 9.11 Epithelial cystic vacuolation (rat), sometimes referred to as cribriform change or pseudo-gland formation, is often seen at the junction between the distal corpus and cauda epididymis. ×100.

Age-related lesions: testes and epididymides

Increased germ cell degeneration or increased numbers of tubules with germ cell depletion occur in the testis with increasing age, but generally spermatogenesis remains relatively efficient throughout the entire life of the rat and mouse. Minimal, diffuse hyperplasia may accompany the decline in spermatogenesis as a secondary hormonal response.

The most common age-related testicular findings include degenerative and inflammatory lesions of the vasculature, including fibrinoid necrosis, hypertrophy and inflammation of the vascular wall as part of the more generalized condition of polyarteritis nodosa (Fig. 9.12a). Lymphoid aggregates within the interstitium of the rat epididymis are common (Fig. 9.12b). The testis is also a common site for deposition of amyloid in systemic amyloidosis of the aging mouse (Fig. 9.13). Focal proliferative changes in the Leydig cell population (hyperplasia and tumors) (Fig. 9.14) are very common in the F344 rat, and are also present at a lower incidence in other strains of rats and mice. Another common proliferative lesion in the mouse testis is hyperplasia of the rete epithelium (Fig. 9.15). Lipofuscin pigmentation is associated with aging and is observed in the interstitial macrophages and Leydig cells.

FIGURE 9.12a Fibrinoid necrosis of arteriolar walls and periarteritis in the interstitial vasculature of the testis of an aging rat. ×100.

FIGURE 9.12b Lymphoid aggregates within in the interstitium of the rat epididymis are common. ×100.

FIGURE 9.13 Amyloid deposition in the interstitial compartment of a mouse testis. The testis is a common site for amyloidosis. ×100.

FIGURE 9.14 Focal Leydig cell hyperplasia and Leydig cell tumors are very common in some strains of rat (F344), but are also seen at a low incidence in other strains of rats and mice. ×100.

FIGURE 9.15 Hyperplasia of the rete epithelium in the mouse. The normal low cuboidal epithelium has been replaced by a tall columnar hyperplastic epithelium. ×100.

In the aging rat, the segment of the epididymis at the junction between the caput and corpus commonly develops a foamy, basophilic vacuolation within the epithelium (Fig. 9.16). This probably represents the normal glycoprotein secretory product that has become modified in the aging rat. If the cystic rete testis is filled with spermatozoa, the lesion is referred to as a spermatocoele. Spermatocoeles are also common at the junction between the epididymis and vas deferens.

FIGURE 9.16 Basophilic vacuolation is a common age-related change in the epididymal epithelium of rats. It only occurs in one region of the epididymis that is at the junction of the caput and corpus. ×200.

Age-related lesions: accessory sex organs and penis

Urogenital infections affecting the penis, preputial glands, prostate, coagulating glands and seminal vesicles are common in aging rodents, particularly in mice (Suwa et al 2001). Acute or chronic active inflammation with abscess formation (Figs 9.17a, 9.18) may be present throughout the genital tract (Fig. 9.17a). Focal epithelial hyperplasia is observed in the aging rat prostate (Fig. 9.17b).

FIGURE 9.17a Purulent inflammation with regenerative epithelial hyperplasia of the ventral prostate in an aging rat with a urogenital infection. ×100.

FIGURE 9.18 Chronic inflammation of the rat preputial gland. ×100.

FIGURE 9.17b Epithelial hyperplasia in the acinus of the rat prostate. ×200.

In the accessory sex organs, common age-related lesions include distension of the seminal vesicles with degradation of the seminal fluid (Fig. 9.19) or contraction of the vesicles with atrophy of the epithelium. The prostate also shows progressive acinar atrophy and mineralized concretions in the acinar lumina (Fig. 9.20). Cystic dilatation of the preputial gland ducts with secretion or cystic atrophy of the acini are common findings in both rats and mice (Figs 9.21, 9.22). Similar cystic dilation can also be seen in the bulbourethral gland (Fig. 9.23).

FIGURE 9.19 Grossly distended seminal vesicle of a mouse with degradation of the secretory product. ×100.

FIGURE 9.20 Mineralized concretions and progressive acinar atrophy of the prostate are common age-related findings in the rat. ×100.

FIGURE 9.21 Rat preputial gland with cystic dilatation of the duct with secretion. This often results in gross enlargement of the gland. ×100.

FIGURE 9.22 Mouse preputial gland with cystic atrophy of the acini. ×100.

FIGURE 9.23 Cystic dilatation of the bulbourethral gland of a rat, which is expanded with secretion. ×200.

Immaturity, peripuberty, maturity

Dogs mature over a relatively wide age range (seven to twelve months of age), with most reaching sexual maturity by ten months of age. The age of sexual maturity is also influenced by the supplier. Dorso and coworkers (2008) reported that 90% of dogs 31–40 weeks of age supplied by Harlan, France, were sexually mature compared with only 10% of dogs of the same age supplied by Marshall Farms, USA. Dogs less than ten months of age usually show a range of degenerative morphologies reflecting ongoing maturation. Dogs on the borderline of maturity will have varying numbers of degenerating, missing and sloughed germ cells in the testis and the epididymal lumina and some tubules may be vacuolated, contracted or dilated. The appearance of the testes and epididymal contents can be indistinguishable from chemically-induced toxicity, and evaluating the relationship of such changes to treatment is made more difficult by the small number of animals in each group. The confusion can be avoided by ensuring that dogs are at least ten months and preferably 12 months of age at the end of the study. The morphological characteristics of the developing dog testis and epididymis are illustrated in Figs 9–.24-9.29 and Figs 9.30–9.34 respectively.

FIGURE 9.24 Totally quiescent testis from a dog, five to six months of age. Tubules are lined by Sertoli cells interspersed with occasional gonocytes. There is no lumen within the tubules because fluid is not yet being secreted. ×100.

FIGURE 9.25 Testis from a dog, five to six months old, where the Sertoli cells are just beginning to secrete fluid which is forming vacuoles within the Sertoli cell lining and producing a lumen in the gradually expanding tubules. The gonocytes are proliferating to form spermatogonia, some of which are apoptotic. ×100.

FIGURE 9.26 Testis from a dog, six to seven months old. The tubules are progressively expanding due to the fluid secreted by the Sertoli cells and there are numerous fluid-filled vacuoles within the Sertoli cell lining. Spermatogonia and early spermatocytes can be seen in the tubules, many of which are undergoing apoptosis. ×100.

FIGURE 9.27 Testis from a dog, six to nine months old. The tubules are variously populated with germ cells extending up to round spermatids. Spermatogenesis is still patchy in most tubules, and many of the newly developed germ cells are degenerating or being sloughed into the lumen. ×20.

FIGURE 9.28 Testis from a dog, six to nine months of age. Most tubules have layers of germ cells up to pachytene spermatocytes or round spermatids. There are also occasional elongating spermatids. Degenerating and sloughed germ cells are fewer but still quite frequent. ×200.

FIGURE 9.29 Testis from a 12-month-old dog. All tubules have complete spermatogenesis and have a full complement of elongating spermatids the tails of which fill the lumen. Occasional degenerate cells are still present but they are infrequent. ×200.

FIGURE 9.30 Cauda epididymis from a dog, five to six months of age. The ductal diameter is small due to lack of any fluid secretion by the testis. There are no sloughed cells or cell debris.

FIGURE 9.31 Cauda epididymis from a dog, six to eight months of age. The ductal lumen is beginning to expand and contains a small amount of fluid and sloughed germ cells from the testis.

FIGURE 9.32 Cauda epididymis from a dog, six to eight months of age. The luminal diameter is gradually increasing and contains fluid and cells.

FIGURE 9.33 Cauda epididymis from a dog, 10–12 months of age. The ductal lumen is fully expanded with sperm and there are only occasional sloughed germ cells.

FIGURE 9.34 Caput epididymis from a dog, six to eight months of age. The ducts are filled with sloughed, apoptotic and degenerating germ cells from the developing testis but there are no sperm. Sloughed cells are more obvious in the head than the tail of the epididymis. ×200.

Unlike the rodent, the dog goes through a developmentally quiescent period with respect to testicular development. During this period, the seminiferous tubules are lined by Sertoli cells and small numbers of gonocytes (pre-spermatogonia) which do not begin development until around five months of age (Fig. 9.24). At that time the gonocytes begin to proliferate and produce spermatogonia which will populate the basal layer of the seminiferous tubule and initiate the process of spermatogenesis. At the same time, the Sertoli cell resumes its maturation and begins to secrete seminiferous tubule fluid. This often takes the form of fluid-filled vacuoles within the layer of Sertoli cells and the gradual formation of a tubular lumen and expansion of the overall tubular diameter (Figs 9.25, 9.26). Spermatogonia begin to proliferate and produce spermatocytes, which in turn divide and produce round spermatids. The round spermatids gradually elongate and mature into the final whip-like mature spermatids, which are released into the tubular lumina. From there they are transported on into the epididymis. Spermatogenesis does not develop at the same rate in all tubules, and so different tubules will be more or less advanced than others and because the Sertoli and germ cells are not yet up to full functional efficiency, there will be considerable degeneration and sloughing of germ cells in this first cycle of spermatogenesis (Fig. 9.27). The gradual increase in seminiferous tubule fluid production and the high rate of germ cell attrition is reflected by the luminal contents of the epididymis (Figs 9.30–34). Small-diameter, empty ducts will gradually expand with fluid and contain degenerate sloughed germ cells through to puberty (Fig. 9.34), to be replaced by expanded ducts filled with mature sperm and relatively few degenerate cells in the fully mature adult (Fig. 9.33).

Identifying the status of sexual maturation in the dog testis should be done on the basis of the presence of sperm in the corpus and cauda epididymis (the caput does not concentrate sperm sufficiently to be able to visualize it) and the presence and number of elongating spermatids in the testis. The size and secretory activity of the prostate is not very useful for identifying maturity because the prostate matures at a different rate.

Lesions seen in young mature animals: testes

Changes that can easily be confused with immaturity, but which are background degenerative changes of the sexually mature dog, are seen commonly in dogs that are more than 10 months of age. The changes have been described by Rehm and coworkers (2000) and by Goedken and coworkers (2008). The most common findings are tubular hypospermatogenesis and tubular hypoplasia/atrophy, both of which have an approximately 30% incidence in normal dogs. Hypospermatogenesis is characterized by the absence of one or more generations of germ cells from the seminiferous epithelium (Figs 9.35, 9.36). Hypospermatogenesis may be distinguished from immaturity by the fact that many of the tubules will have a layer of mature, elongate spermatids at the luminal surface, but with the underlying layer of round spermatids and/or layer of pachytene spermatocytes missing or partially depleted. This is indicative of transient (cyclical) inhibition of spermatogonial division and is different from the pattern of germ cell degeneration and patchy germ cell depletion typical of immaturity (compare with Fig. 9.27). Hypospermatogenesis can range in severity from minimal (<10% tubules affected) to severe (>75% tubules affected). Most testes will have a few tubules affected by hypospermatogenesis.

FIGURE 9.35 Stage VI tubule with hypospermatogenesis (*). This tubule is in the same stage of spermatogenesis as the other two tubules (identifiable by the shape of the elongating spermatids). Although this tubule contains a normal population of elongating spermatids, it lacks the underlying layers of pachytene and prepachytene spermatocytes that are present in the other two tubules. ×200.

FIGURE 9.36 Stage V tubule with hypospermatogenesis (*). The tubule on the left is at the same stage. Although the elongating spermatid population is normal in the hypospermatogenic tubule, it is almost entirely missing the underlying layers of round spermatids, pachytene spermatocytes and spermatogonia that are present in the normal stage V tubule. ×200.

Segmental hypoplasia is typically seen as a discrete group of contracted tubules, often in a wedge shape and situated in a subcapsular location, which are completely devoid of germ cells (Fig. 9.37). These tubules give the appearance of never having been populated by germ cells, hence the term hypoplasia. The lobular distribution suggests that the group of tubular profiles belong to a single, coiled, seminiferous tubule.

FIGURE 9.37 Tubular hypoplasia typically presents as a triangular wedge of contracted tubules lined only by Sertoli cells. The surrounding tubules show normal spermatogenesis. The affected tubules have the appearance of never having been populated with germ cells. ×100.

Other common background findings in the adult dog testis include swollen spermatocytes. These are probably secondary spermatocytes which have failed to complete their second meiotic division and remain sequestered in the germinal epithelium, arrested in meiosis, while the surrounding cells continue their development into round spermatids (Fig. 9.38). Occasional multinucleate germ cells, which represent degenerating spermatocytes or spermatids, are also a common feature of dog testes (Fig. 9.39). Both findings can usually be seen in a few tubules from most dog testes.

FIGURE 9.38 Tubules containing large, ‘swollen’, densely staining spermatocytes (arrowed). Most testes will have a few tubules that contain these cells. They probably represent secondary spermatocytes which have failed to complete their second meiotic division and have become arrested in their development while the rest of the cells in the tubule continue maturation. ×200.

FIGURE 9.39 A few multinucleate giant cells, which represent degenerating spermatids or spermatocytes, may be found in most mature dog testes. ×200.

Orchitis, characterized by a lymphocytic or mixed inflammatory cell infiltrate in the interstitium of the testis, may occasionally be seen in the dog testes (Fig. 9.40) (Fritz et al 1976). The inflammation may also extend into the tubular epithelium, resulting in destruction of the affected tubules. The lesion is generally accompanied by a lymphocytic inflammation in the epididymis (Fig. 9.41) and in some cases is genetically associated with lymphocytic thyroiditis (Fritz et al 1976). The lesion is thought to have an autoimmune etiology.

FIGURE 9.40 Lymphocytic orchitis is an uncommon background finding in the dog. The infiltrating lymphocytes and macrophages often penetrate and destroy seminiferous tubules in the affected areas. ×100.

FIGURE 9.41 Lymphocytic epididymitis often accompanies lymphocytic orchitis. ×100.

Lesions observed in young mature animals: testes

The sperm content of the dog epididymis varies depending on location. Sperm is generally not seen in the efferent ducts or the head of the epididymis because it is very dilute. Sperm becomes visible in the distal cauda and appears dense throughout the corpus. Sperm content within the large-diameter ducts of the cauda can be variable and may often be missing due to loss during processing. The sperm content of the corpus and proximal cauda should be used to evaluate normal sperm content and maturity status.

Sperm stasis, sometimes accompanied by inflammation, is a common finding in the efferent ducts situated in the head of the epididymis, and probably represents impaction of sperm in blind-ending efferent ducts (Fig. 9.42) (Foley et al 1995). True sperm granulomas, similar to those seen in rodents, also occur throughout the epididymis.

FIGURE 9.42 The efferent ducts are embedded in the head of the dog epididymis and some are blind-ending. This may result in sperm stasis and dilation. ×100.

Cribriform change, characterized by infolding of the ductal epithelium with the formation of pseudoglandular cysts (Fig. 9.43), is often observed at the corpus/caudal junction. This is similar to the lesion in rodents. Intranuclear eosinophilic inclusion bodies are a feature of the canine epididymis (Fig. 9.44), particularly in the caput, although their significance is unknown.

FIGURE 9.43 Cribriform change or ‘pseudoglandular’ cysts are frequently present at the junction between the distal corpus and cauda epididymis of the dog. ×100.

FIGURE 9.44 Intranuclear eosinophilic inclusions are commonly seen in the epithelial cells of the caput epididymis of the dog. Their significance is unknown. ×200.

Interstitial lymphocytic infiltrates are common and may also be accompanied by arteritis or periarteritis either in the interstitium or in the surrounding adipose tissue of the dog epididymis. This is a common site for arteritis associated with the more generalized condition of ‘beagle pain syndrome’. Epithelial hyperplasia of the ductus epididymis is a normal feature of the aged beagle dog epididymis (James & Heywood 1979).