- Email: [email protected]
Spontaneous tubular (cuboidal) metaplasia of the parietal layer of Bowman's capsule in Cynomolgus monkeys (Macaca fascicularis)
ARTICLE IN PRESS Journal of Experimental Animal Science Journal of Experimental Animal Science 43 (2004) 13–17 www.elsevier-deutschland.de/jeas
SHORT COMMUNICATION
Spontaneous tubular (cuboidal) metaplasia of the parietal layer of Bowman’s capsule in Cynomolgus monkeys (Macaca fascicularis) J. Kaspareit*, S. Friderichs-Gromoll, E. Buse, G. Habermann Covance Laboratories, Department of Pathology, Kesselfeld 29, Munster 48163, Germany .
Abstract Tubular (cuboidal) metaplasia of the parietal epithelium of Bowman’s capsule was observed in 19 (10 males, 9 females) of 56 adult control Cynomolgus monkeys. Cuboidal epithelium replaced the normally present flattened epithelium to various degrees in animals affected. Cuboidal cells revealed an eosinophilic cytoplasm and vesicular nuclei, thus resembling proximal convoluted epithelial cells in all respects. Continuity of the cuboidal glomerular epithelium with that of the proximal tubule was occasionally observed. r 2004 Elsevier GmbH. All rights reserved. Keywords: Bowman’s capsule; Glomerulum; Parietal layer; Cuboidal metaplasia; Tubular metaplasia; Primate; Cynomolgus monkey
Introduction The normal renal corpuscle consists of a glomerulus surrounded by visceral and parietal layers of cells known as Bowman’s capsule. The parietal layer of Bowman’s capsule normally is a layer of simple flattened epithelium (Fig. 1). In addition to this type of epithelium, a high cuboidal type, structurally resembling proximal tubular epithelium and covering parts to the entire parietal surface, has been reported in other common laboratory animal species like mice (Liebelt, 1986), rats, (Jakowski, *Corresponding author. Tel.: +49-251-9798148; fax: +49-252-784697. E-mail address: [email protected] (J. Kaspareit). 0939-8600/$ - see front matter r 2004 Elsevier GmbH. All rights reserved. doi:10.1016/j.jeas.2004.01.001
ARTICLE IN PRESS 14
J. Kaspareit et al. / Journal of Experimental Animal Science 43 (2004) 13–17
Fig. 1. Normal glomerulum with a parietal layer of Bowman’s capsule lined by a simple squamous epithelium in a Cynomolgus monkey (HE, 300).
1982; Haensly et al., 1982; Haley and Bulger, 1983; Castello and Goya, 1990), dogs . (Mollendorf, 1930) and in the human kidney (Reidborn, 1968; Ward, 1970; Haensly and Lee, 1986; Haensly, 1988). In inbred strains of mice this change has been called a male hormone-dependant feature since it is commonly seen in adult male mice or mice treated with male hormones (Liebelt, 1986). In rats the lesion has been associated with the aging process (Castello and Goya, 1990; Haley and Bulger, 1983), hypertension (Haensly et al., 1982) and unilateral nephrectomy (Andrews, 1981). In several reports attempts have been undertaken to associate the metaplasia of the parietal layer of Bowman’s capsule with different disease conditions like malignant tumors, alcoholic liver disease or hypertension (Reidborn, 1968; Haensly and Lee, 1986; Haensly, 1988) in men. However, since it was also observed in patients without any primary diseases that died by traffic accidents (Ward, 1970) it rather was considered to be a spontaneous lesion. The histomorphological features of the lesion seen for the first time in Cynomolgus monkeys are described in the present report and compared with other laboratory animal species.
ARTICLE IN PRESS J. Kaspareit et al. / Journal of Experimental Animal Science 43 (2004) 13–17
15
Fig. 2. Glomerulum affected by low-grade tubular (cuboidal) metaplasia of the parietal layer of Bowman’s capsule (arrow) in a Cynomolgus monkey (HE, 300).
Material and methods A total of 56 untreated adult control Cynomolgus monkeys (29 males, 27 females) were examined to estimate the approximate incidence and histomorphological appearance of tubular metaplasia of the parietal layer of Bowman’s capsule in the kidney. Animals were randomly selected from several different toxicity studies. They were born and raised in primate colonies in China and Mauritius. The oldest animal examined was 6 years and 3 months old. They were housed individually in stainless steel cages in climate controlled animal rooms that provided a minimum of 10 air changes/h. The temperature and the relative humidity ranged between 19 C and 25 C and 30–80% respectively. Artificial lightning was controlled to give a cycle of 12 h dark and 12 h light. Each animal was offered twice daily a commercial diet for primates (Sniff P10, Sniff, Soest, Germany). In addition, the animals received fresh fruits twice weekly and one slice of bread once weekly. Tap water was provided ad libitum via an automatic watering system.
ARTICLE IN PRESS 16
J. Kaspareit et al. / Journal of Experimental Animal Science 43 (2004) 13–17
A complete necropsy was performed on all animals. All organs were fixed in 10% buffered formalin. Samples of tissue were embedded in paraffin wax, sectioned at a nominal thickness of 5 mm and stained with hematoxilin and eosin.
Results and discussion Cuboidal or tubular metaplasia of the parietal layer of Bowman’s capsule was observed in 19 (10 males, 9 females) of 56 monkeys examined. There was a great inter-individual variability between the animals. In the great majority of kidneys only few (or even only one) glomeruli partly lined by a cuboidal epithelium (Fig. 2) were uni- or bilaterally observed. In one single animal more than 50% of the glomeruli displayed high-grade metaplasia. In this animal the whole circumference of the parietal layer of Bowman’s capsule was lined by cuboidal epithelium in most affected glomeruli (Fig. 3). The cuboidal cells lining the parietal layer had an eosinophilic cytoplasm and vesicular nuclei, thus resembling closely the histological
Fig. 3. Two adjacent glomeruli affected by high-grade tubular (cuboidal) metaplasia of the parietal layer of Bowman’s capsule in a Cynomolgus monkey (HE, 300).
ARTICLE IN PRESS J. Kaspareit et al. / Journal of Experimental Animal Science 43 (2004) 13–17
17
appearance of proximal convoluted tubular epithelial cells. In all glomeruli affected by lower grades of metaplasia, changes were seen opposite to the vascular pole. Occasionally, it could be seen that the cuboidal parietal layer epithelium was continuous with the proximal tubule epithelium. A strong sexual dimorphism of cuboidal parietal epithelium in Bowman’s capsules has been observed in several inbred strains (Liebelt, 1986), but was also observed in adult Long-Evans rats (Jakowski, 1982) and in old Sprague–Dawley rats (Castello and Goya, 1990). Generally, the males are the sex with higher incidence and/or severity of the lesion. In contrast to that findings metaplasia of parietal glomerular cells was found with about equal incidence in both sexes of Cynomolgus monkeys. Therefore an influence of sexual hormones on the lesions described seems to be rather unlikely. An age-dependency of the glomerular lesion has been seen in Sprague–Dawley rats (Castello and Goya, 1990) and in SHR-rats (Haensly et al., 1982). Cynomolgus monkeys of the toxicological studies examined for the present report were adult (4–5.5 years old) with little variation of age. However, since the animal with the severest glomerular lesions was also the oldest primate examined, a progression of the lesion with age cannot be completely excluded. Further studies, including a significant group of aged Cynomolgus monkeys, will be necessary to clarify this question. To the best knowledge of the authors, tubular (cuboidal) metaplasia of the parietal epithelium of Bowman’s capsule is described for the first time in Cynomolgus monkeys in this report. Especially, those working with Cynomolgus monkeys in toxicological studies should be aware of the existence of this spontaneous lesion also in primates to avoid misinterpretation as an induced or treatment-related change.
References Andrews, P.M., 1981. The presence of proximal tubule-like cells in the kidney parietal epithelium in response to unilateral nephrectomy. Anat. Rec. 200, 61–65. Castello, L., Goya, R.G., 1990. Sex-related tubular metaplasia in Bowman’s capsule of aging rats. Virchows Arch. B Cell. Pathol. 59, 79–82. Haensly, W.E., 1988. Metaplasia of the parietal layer of Bowman’s capsule in the human kidney: incidence in alcoholic liver disease and hypertension. Histol. Histopathol. 3, 235–240. Haensly, W.E., Lee, J.C., 1986. Metaplasia of the parietal layer of Bowman’s capsule: a histopathological survey of the human kidney. Histol. Histopathol. 1, 363–367. Haensly, W.E., Granger, H.J., Morris, A.C., Cioffe, C., 1982. Proximal tubule-like epithelium in Bowman’s capsule in spontaneous hypertensive rats. Am J. Pathol. 107, 92–97. Haley, D.P., Bulger, R.E., 1983. The aging male rat: structure and function of the kidney. Am. J. Anat. 167, 1–13. Jakowski, R.M., 1982. Renal tubular epithelium lining parietal layer of Bowman’s capsule in adult LongEvans rats. Vet. Pathol. 19, 212–215. Liebelt, A.G., 1986. Unique features of anatomy, histology, and ultrastructure, kidney, mouse. In: Jones, T.C., Mohr, U., Hunt, R.D. (Eds.), Urinary System. Springer, Berlin, pp. 24–44. . . Mollendorf, W.v., 1930. Exkretionsapparat und weibliche Genitalorgane. In: Mollendorf, W.v (Ed.), Handbuch der Mikroskopischen Anatomie des Menschen, Part 1. Springer, Berlin, pp. 61–65. Reidborn, H.E., 1968. Metaplasia of the parietal layer of Bowman’s capsule. Am. J. Clin. Pathol. 50, 240–242. Ward, A.M., 1970. Tubular metaplasia in Bowman’s capsule. J. Clin. Pathol. 23, 472–474.
SHORT COMMUNICATION
Spontaneous tubular (cuboidal) metaplasia of the parietal layer of Bowman’s capsule in Cynomolgus monkeys (Macaca fascicularis) J. Kaspareit*, S. Friderichs-Gromoll, E. Buse, G. Habermann Covance Laboratories, Department of Pathology, Kesselfeld 29, Munster 48163, Germany .
Abstract Tubular (cuboidal) metaplasia of the parietal epithelium of Bowman’s capsule was observed in 19 (10 males, 9 females) of 56 adult control Cynomolgus monkeys. Cuboidal epithelium replaced the normally present flattened epithelium to various degrees in animals affected. Cuboidal cells revealed an eosinophilic cytoplasm and vesicular nuclei, thus resembling proximal convoluted epithelial cells in all respects. Continuity of the cuboidal glomerular epithelium with that of the proximal tubule was occasionally observed. r 2004 Elsevier GmbH. All rights reserved. Keywords: Bowman’s capsule; Glomerulum; Parietal layer; Cuboidal metaplasia; Tubular metaplasia; Primate; Cynomolgus monkey
Introduction The normal renal corpuscle consists of a glomerulus surrounded by visceral and parietal layers of cells known as Bowman’s capsule. The parietal layer of Bowman’s capsule normally is a layer of simple flattened epithelium (Fig. 1). In addition to this type of epithelium, a high cuboidal type, structurally resembling proximal tubular epithelium and covering parts to the entire parietal surface, has been reported in other common laboratory animal species like mice (Liebelt, 1986), rats, (Jakowski, *Corresponding author. Tel.: +49-251-9798148; fax: +49-252-784697. E-mail address: [email protected] (J. Kaspareit). 0939-8600/$ - see front matter r 2004 Elsevier GmbH. All rights reserved. doi:10.1016/j.jeas.2004.01.001
ARTICLE IN PRESS 14
J. Kaspareit et al. / Journal of Experimental Animal Science 43 (2004) 13–17
Fig. 1. Normal glomerulum with a parietal layer of Bowman’s capsule lined by a simple squamous epithelium in a Cynomolgus monkey (HE, 300).
1982; Haensly et al., 1982; Haley and Bulger, 1983; Castello and Goya, 1990), dogs . (Mollendorf, 1930) and in the human kidney (Reidborn, 1968; Ward, 1970; Haensly and Lee, 1986; Haensly, 1988). In inbred strains of mice this change has been called a male hormone-dependant feature since it is commonly seen in adult male mice or mice treated with male hormones (Liebelt, 1986). In rats the lesion has been associated with the aging process (Castello and Goya, 1990; Haley and Bulger, 1983), hypertension (Haensly et al., 1982) and unilateral nephrectomy (Andrews, 1981). In several reports attempts have been undertaken to associate the metaplasia of the parietal layer of Bowman’s capsule with different disease conditions like malignant tumors, alcoholic liver disease or hypertension (Reidborn, 1968; Haensly and Lee, 1986; Haensly, 1988) in men. However, since it was also observed in patients without any primary diseases that died by traffic accidents (Ward, 1970) it rather was considered to be a spontaneous lesion. The histomorphological features of the lesion seen for the first time in Cynomolgus monkeys are described in the present report and compared with other laboratory animal species.
ARTICLE IN PRESS J. Kaspareit et al. / Journal of Experimental Animal Science 43 (2004) 13–17
15
Fig. 2. Glomerulum affected by low-grade tubular (cuboidal) metaplasia of the parietal layer of Bowman’s capsule (arrow) in a Cynomolgus monkey (HE, 300).
Material and methods A total of 56 untreated adult control Cynomolgus monkeys (29 males, 27 females) were examined to estimate the approximate incidence and histomorphological appearance of tubular metaplasia of the parietal layer of Bowman’s capsule in the kidney. Animals were randomly selected from several different toxicity studies. They were born and raised in primate colonies in China and Mauritius. The oldest animal examined was 6 years and 3 months old. They were housed individually in stainless steel cages in climate controlled animal rooms that provided a minimum of 10 air changes/h. The temperature and the relative humidity ranged between 19 C and 25 C and 30–80% respectively. Artificial lightning was controlled to give a cycle of 12 h dark and 12 h light. Each animal was offered twice daily a commercial diet for primates (Sniff P10, Sniff, Soest, Germany). In addition, the animals received fresh fruits twice weekly and one slice of bread once weekly. Tap water was provided ad libitum via an automatic watering system.
ARTICLE IN PRESS 16
J. Kaspareit et al. / Journal of Experimental Animal Science 43 (2004) 13–17
A complete necropsy was performed on all animals. All organs were fixed in 10% buffered formalin. Samples of tissue were embedded in paraffin wax, sectioned at a nominal thickness of 5 mm and stained with hematoxilin and eosin.
Results and discussion Cuboidal or tubular metaplasia of the parietal layer of Bowman’s capsule was observed in 19 (10 males, 9 females) of 56 monkeys examined. There was a great inter-individual variability between the animals. In the great majority of kidneys only few (or even only one) glomeruli partly lined by a cuboidal epithelium (Fig. 2) were uni- or bilaterally observed. In one single animal more than 50% of the glomeruli displayed high-grade metaplasia. In this animal the whole circumference of the parietal layer of Bowman’s capsule was lined by cuboidal epithelium in most affected glomeruli (Fig. 3). The cuboidal cells lining the parietal layer had an eosinophilic cytoplasm and vesicular nuclei, thus resembling closely the histological
Fig. 3. Two adjacent glomeruli affected by high-grade tubular (cuboidal) metaplasia of the parietal layer of Bowman’s capsule in a Cynomolgus monkey (HE, 300).
ARTICLE IN PRESS J. Kaspareit et al. / Journal of Experimental Animal Science 43 (2004) 13–17
17
appearance of proximal convoluted tubular epithelial cells. In all glomeruli affected by lower grades of metaplasia, changes were seen opposite to the vascular pole. Occasionally, it could be seen that the cuboidal parietal layer epithelium was continuous with the proximal tubule epithelium. A strong sexual dimorphism of cuboidal parietal epithelium in Bowman’s capsules has been observed in several inbred strains (Liebelt, 1986), but was also observed in adult Long-Evans rats (Jakowski, 1982) and in old Sprague–Dawley rats (Castello and Goya, 1990). Generally, the males are the sex with higher incidence and/or severity of the lesion. In contrast to that findings metaplasia of parietal glomerular cells was found with about equal incidence in both sexes of Cynomolgus monkeys. Therefore an influence of sexual hormones on the lesions described seems to be rather unlikely. An age-dependency of the glomerular lesion has been seen in Sprague–Dawley rats (Castello and Goya, 1990) and in SHR-rats (Haensly et al., 1982). Cynomolgus monkeys of the toxicological studies examined for the present report were adult (4–5.5 years old) with little variation of age. However, since the animal with the severest glomerular lesions was also the oldest primate examined, a progression of the lesion with age cannot be completely excluded. Further studies, including a significant group of aged Cynomolgus monkeys, will be necessary to clarify this question. To the best knowledge of the authors, tubular (cuboidal) metaplasia of the parietal epithelium of Bowman’s capsule is described for the first time in Cynomolgus monkeys in this report. Especially, those working with Cynomolgus monkeys in toxicological studies should be aware of the existence of this spontaneous lesion also in primates to avoid misinterpretation as an induced or treatment-related change.
References Andrews, P.M., 1981. The presence of proximal tubule-like cells in the kidney parietal epithelium in response to unilateral nephrectomy. Anat. Rec. 200, 61–65. Castello, L., Goya, R.G., 1990. Sex-related tubular metaplasia in Bowman’s capsule of aging rats. Virchows Arch. B Cell. Pathol. 59, 79–82. Haensly, W.E., 1988. Metaplasia of the parietal layer of Bowman’s capsule in the human kidney: incidence in alcoholic liver disease and hypertension. Histol. Histopathol. 3, 235–240. Haensly, W.E., Lee, J.C., 1986. Metaplasia of the parietal layer of Bowman’s capsule: a histopathological survey of the human kidney. Histol. Histopathol. 1, 363–367. Haensly, W.E., Granger, H.J., Morris, A.C., Cioffe, C., 1982. Proximal tubule-like epithelium in Bowman’s capsule in spontaneous hypertensive rats. Am J. Pathol. 107, 92–97. Haley, D.P., Bulger, R.E., 1983. The aging male rat: structure and function of the kidney. Am. J. Anat. 167, 1–13. Jakowski, R.M., 1982. Renal tubular epithelium lining parietal layer of Bowman’s capsule in adult LongEvans rats. Vet. Pathol. 19, 212–215. Liebelt, A.G., 1986. Unique features of anatomy, histology, and ultrastructure, kidney, mouse. In: Jones, T.C., Mohr, U., Hunt, R.D. (Eds.), Urinary System. Springer, Berlin, pp. 24–44. . . Mollendorf, W.v., 1930. Exkretionsapparat und weibliche Genitalorgane. In: Mollendorf, W.v (Ed.), Handbuch der Mikroskopischen Anatomie des Menschen, Part 1. Springer, Berlin, pp. 61–65. Reidborn, H.E., 1968. Metaplasia of the parietal layer of Bowman’s capsule. Am. J. Clin. Pathol. 50, 240–242. Ward, A.M., 1970. Tubular metaplasia in Bowman’s capsule. J. Clin. Pathol. 23, 472–474.