A spontaneously occurring malignant ovarian Sertoli cell tumor in a young Sprague Dawley rat

Primary ovarian tumors are generally uncommon in rats used in toxicologic studies. A malignant Sertoli cell tumor was present in the ovary of a 19-week-old female Sprague Dawley rat. Macroscopically, the mass was white and firm, 10 × 13 × 17 mm in size, and located in the right ovary. Histopathologically, the mass was composed of nests of pleomorphic cells, which formed seminiferous-like tubules separated by a thin fibrovascular stroma. The tubules were lined by tumor cells, which had basally located nuclei and abundant eosinophilic and vacuolated cytoplasm. In some areas, the tumor cells were arranged in a retiform growth pattern, mimicking a rete testis/ovarii. Disseminated metastases to the surfaces of the mesentery, spleen and liver were also present. Immunohistochemically, many tumor cells were strongly positive for vimentin, estrogen receptor α and Ki 67. Some tumor cells were positive for pancytokeratin and inhibin α. These findings closely resemble those of an ovarian-derived human malignant Sertoli cell tumor. From our review of the literature, we believe this is the first report of a spontaneous malignant Sertoli cell tumor in the ovary of a young laboratory rat. This case might provide useful historical control information for rat toxicity studies.     

地顶孢霉培养物对大鼠生长性能、血清与肝脏抗氧化及免疫指标的影响

本试验旨在研究地顶孢霉培养物对大鼠生长性能、血清与肝脏抗氧化以及免疫指标的影响。选用体重相近的SD大鼠40只,随机分成5组,每组8个重复,每个重复1只大鼠。5组分别是对照组和4个不同地顶孢霉培养物剂量组(10、50、250和1 250 mg/kg BW组),连续灌胃21 d。结果表明:地顶孢霉培养物极显著提高大鼠的平均日增重(P0.01);提高了大鼠肝脏指数、胸腺指数;提高了大鼠血清中总蛋白(TP)、白蛋白(ALB)、球蛋白(GLB)和葡萄糖(GLU)含量,降低了谷丙转氨酶(ALT)、谷草转氨酶(AST)活力和低密度脂蛋白(LDL)含量;提高了血清和肝脏中谷胱甘肽过氧化物酶(GSH-Px)活力和总抗氧化能力(T-AOC),降低丙二醛(MDA)含量,同时提高了肝脏中的总超氧化物歧化酶(T-SOD)含量;提高了血清免疫球蛋白A、免疫球蛋白G和免疫球蛋白M含量,同时提高血清和肝脏中白介素-4(IL-4)含量,降低白介素-1β(IL-1β)和白介素-17(IL-17)含量。综合各项指标,地顶孢霉培养物能够提高SD大鼠平均日增重,改善血清生化指标,提高大鼠机体抗氧化能力和免疫能力,其中以250 mg/kg BW的添加量为最佳。     

A case of spontaneous rete testis adenoma in a Sprague–Dawley rat

A 104-week-old male CD (SD) rat exhibited enlargement of the left testis. Microscopically, this mass was demarcated from the testis by fibrous connective tissue and characterized by cystic dilatation with single-layered columnar cells and papillary proliferation connected to the solid growth area without clear boundaries. In the solid growth area, cells were dissected into irregular alveolar nests by scant fibrous tissue with small blood vessels. The nuclei of proliferating cells were variable in size and round- to oval-shaped, and their cytoplasm was pale or eosinophilic and sometimes contained vacuoles or eosinophilic granules. Immunohistochemically, the tumor cells were positive for vimentin and cytokeratin (CK) 7. Since CK7 was exclusively positive in the rete testis epithelium of the naïve rat, it was valuable to diagnose this tumor as rete testis-originated. Based on these results and the lack of apparent pleomorphism, mitotic figures, and metastasis, the present case was diagnosed as rete testis adenoma.     

Erythrocyte osmotic fragility and general health status of adolescent Sprague Dawley rats supplemented with Hibiscus sabdariffa aqueous calyx extracts as neonates followed by a high‐fructose diet post‐weaning

High‐fructose diets (HFD) can cause oxidative damage to tissues including erythrocyte cell membranes. Hibiscus sabdariffa (HS) has protective antioxidant properties. Rats were used to investigate whether the consumption of HS by neonates would result in long‐term effects on their erythrocyte osmotic fragility (EOF) and general health when later fed a high‐fructose diet post‐weaning through adolescence. Eighty of four‐day‐old Sprague Dawley rat pups were divided randomly into three treatment groups. The controls (n = 27) received distilled water at 10 ml/kg b. w, while the other groups received either 50 mg/kg (n = 28) or 500 mg/kg (n = 25) of an HS aqueous calyx extract orally till post‐natal day 14. The rats in each group were weaned and divided into two subgroups; one continued on normal rat chow, and the other received fructose (20% w/v) in their drinking water for 30 days. Blood was collected in heparinised tubes and added to serially diluted (0.0–0.85%) phosphate‐buffered saline to determine the EOF. Clinical markers of health status were determined with an automated chemical analyser. HS extracts did not programme metabolism in the growing rats to alter their general health and EOF in response to the HFD.     

Uterine torsion in a Sprague Dawley rat (Rattus norvegicus)

Uterine torsion is a twisting of the uterus or uterine horn perpendicular to its long axis. We report a case of uterine torsion in an adult breeding Sprague Dawley rat. The rat died a month after her last recorded delivery. Post mortem examination of the rat revealed 270 degrees torsion of the right uterine horn. The uterus contained a single foetus. The liver was pale and enlarged. The rest of the viscera appeared normal. Histopathological examination showed acute hepatic necrosis and pulmonary congestion with mild lymphocytic infiltrates peribronchially. The acute hepatic necrosis may have been associated with septicaemia due to compromised blood vessels following the uterine torsion. The presence of a single foetus could have resulted in foeto-maternal disproportion with resultant uterine torsion. Torsion of the uterus can be accompanied by haemostatic and metabolic complications, which could have caused the death of the rat. Although uterine torsion is a rare condition in rats, it should be considered as a potential complication of gestation in animal breeding units.     

Zinc glycine chelate absorption characteristics in Sprague Dawley rat

This study was conducted to investigate absorption characteristics of zinc glycine chelate (Zn–Gly) by evaluating tissues zinc status and the expression of zinc transporters in rats. A total of 24 male rats were randomly allocated to three treatments and administered either saline or 35 mg Zn/kg body weight from zinc sulphate (ZnSO₄) or Zn–Gly by feeding tube separately. Four rats per group were slaughtered and tissues were collected at 2 and 6 h after gavage respectively. Our data showed that Zn–Gly did more effectively in increasing (p < 0.05) serum zinc levels, and the activities of serum and liver alkaline phosphatase (ALP) and liver Cu/Zn superoxide dismutase (Cu/Zn SOD) at 2 and 6 h. By 2 h after the zinc load, the mRNA and protein abundance of intestinal metallothionein1 (MT1) and zinc transporter SLC30A1 (ZnT1) were higher (p < 0.05), and zinc transporter SLC39A4 (Zip4) lower (p < 0.05) in ZnSO₄ compared to other groups. Zinc transporter SLC39A5 (Zip5) mRNA expression was not zinc responsive, but Zip5 protein abundance was remarkably (p < 0.05) increased in ZnSO₄ 2 h later. Overall, our results indicated that in short‐term periods, Zn–Gly was more effective in improving body zinc status than ZnSO₄, and ZnSO₄ did more efficiently on the regulation of zinc transporters in small intestine.     

Uterine Carcinosarcoma in a 2-year-old Female Wistar Hannover GALAS Rat

Carcinosarcomas are rare tumors in humans as well as rats and most commonly occur in the uterus. Recently, we observed a case of incidental carcinosarcoma of the uterus in a female Wistar Hannover GALAS [BrlHan:WIST@ Jcl (GALAS)] rat at 2 years of age. Histopathologically, the tumor was characterized by an admixture of malignant epithelial and nonepithelial elements. The carcinomatous components represented a type of endometrial carcinoma, consisting of glandular and solid proliferation of large-sized tumor cells. Prominent mitoses and tumor cell invasion were observed. The sarcomatous components were characterized by multifocal proliferation of severe atypical cells with cartilage matrix and were diagnosed as chondrosarcoma. Transitions between carcinomatous and sarcomatous components were observed, and many tumor cells in the solid lesion showed immunohistochemical reactivity with both cytokeratin and vimentin. Based on these findings, this tumor was diagnosed as a uterine carcinosarcoma. This is the first report of uterine carcinosarcoma in Wistar Hannover GALAS [BrlHan:WIST@Jcl (GALAS)] rats.     

Change Trends of Organ Weight Background Data in Sprague Dawley Rats at Different Ages

Organ weight is one of the most sensitive drug toxicity indicators, and its changes often precede morphological changes. So far, no background data about organ weight and its coefficient in SD rats at different weeks of age have been reported in China. The aim of this study was to summarize and analyze the change trends of organ weight and organ weight coefficients in SD rats at different weeks of age. The absolute of the weights of the brain, spleen, heart, lungs, liver, kidneys, adrenal glands and testes were increased in male SD rats from 13 to 78 weeks, and the weights of the brain, heart, lungs, liver, kidneys and especially the testes were decreased from 78 to 104 weeks. On the other hand, the absolute weight of the adrenal glands showed an increasing trend from 13 to 104 weeks. The absolute weight of the brain, spleen, heart, lungs, liver, kidneys, adrenal glands and ovaries showed an increasing trend from 13 to 104 weeks. A significant increase was observed in adrenal gland and ovary weights, whereas no obvious change trends were observed for the other organ weights mentioned above. It was surprising that the absolute of weight of the adrenal glands and organ-to-brain and organ-to-body weight ratios in female rats were significantly higher than those in males from 13 to 104 weeks. This study was the first to establish background data for organ weights in SD rats at different weeks of age and their reference ranges in line with the experimental animal status in China and to summarize their summarized their changes trend.     

Evaluation of the erythroid regenerative response in two different models of experimentally induced iron deficiency anemia

Anemia was induced in weanling Sprague Dawley rats either by feeding an iron-deficient diet or by chronic phlebotomy. The erythroid regenerative response was then evaluated before and after a hemolytic event, and results were compared with those of a third group of control nonphlebotomized rats fed an iron-replete diet. Diet and phlebotomy groups developed a similar degree of anemia (mean hemoglobin concentration 7.9 g/dL and 7.8 g/dL, respectively; controls, 13.9 g/dL) and hypoferremia (mean serum iron concentration 25.4 microgram/dL and 34.9 microgram/dL, respectively; controls, 222.0 microgram/dL). However, the anemia in diet rats was nonregenerative (reticulocyte count, 83.1 X 10(3) cells/microliter) and associated with bone marrow erythroid hypoplasia; whereas the anemia in phlebotomy rats was regenerative (reticulocyte count, 169.6 X 10(3) cells/microliter) and associated with bone marrow erythroid hyperplasia. Thrombocytosis was seen in diet rats (1,580 X 10(3) cells/microliter) but not phlebotomy rats (901 X 10(3) cells/microliter) when compared with controls (809 X 10(3) cells/microliter). To further evaluate the regenerative capability, phenylhydrazine (PHZ) was administered to induce hemolysis. Erythrocyte mass declined approximately 25% in all groups, including controls. The reticulocytosis (265.3 X 10(3) cells/microliter) seen in phlebotomy rats was earlier and significantly greater than that seen in either diet or control rats. Hemoglobin concentration returned to pre-PHZ concentrations (7.9 g/dL) in phlebotomy rats within 4 days posthemolysis. In diet rats, the maximal regenerative response (176.3 X 10(3) cells/microliter) was not seen until 8 days posthemolysis, and hemoglobin (7.5 g/dL) did not return to pre-PHZ concentrations during the 8-day study. In many aspects, the anemia seen following diet- or phlebotomy-induced iron deficiency was similar. However, the erythroid regenerative capability varied depending on the mechanism by which anemia was induced and furthermore altered the efficiency of hemoglobin production following a hemolytic event. These results suggest that the availability of iron in the diet may modulate the pathogenesis of iron deficiency anemia.     

Natural occurrence of neoplastic lesions in young sprague-dawley rats

It is important for the assessment of toxicological effects of chemicals to know what kinds of neoplasms naturally occur in the early life of experimental animals. In the present study, we demonstrated spontaneous neoplasms in Sprague-Dawley rats used in 4-, 13- and 26-week toxicity studies conducted at Bozo Research Center in the last decade. The tumors, which were first observed in 19-week-old animals, included anterior adenoma of the pituitary, follicular cell adenocarcinoma and C cell adenoma of the thyroids, nephroblastoma of the kidneys, basal cell tumor of the skin and malignant lymphoma. Thereafter, hemangiosarcoma of the tongue, adenocarcinoma of the submandibular glands, histiocytic sarcoma of the spleen, oligodendroglioma of the brain and adenocarcinoma and fibroadenoma of the mammary glands were detected in 32-week-old animals. The incidences of mammary adenocarcinoma and pituitary anterior adenoma were higher than those of other tumors. The present results showed that the same tumors as reported in aged rats could also develop in younger rats.     

Effects of zinc on tissue uptake and toxicity of lead in Sprague Dawley rat

Lead (Pb) exposure occurs together with other metals including zinc (Zn). This study investigated the impact of Zn on Pb tissue accumulation and Pb-induced toxicities. Animals (n=6 rats per group) were exposed to lead acetate (PbAc) or a combination of PbAc and zinc acetate (ZnAc) under the following groups: control (deionized water), low PbAc [12 mg/kg PbAc (3 mg PbAc/rat/day)], low PbAc–ZnAc [12 mg/kg PbAc (3 mg PbAc/rat/day) + 0.2 mg ZnAc/rat/48 hr], high PbAc [120 mg/kg (30 mg PbAc/rat/day)], and high PbAc–ZnAc [120 mg/kg (30 mg PbAc/rat/day) + 1 mg ZnAc/rat/48 hr] for 8 weeks. A significant reduction in body weight gain was observed in the high PbAc group relative to the control group. Muscles and testes both had reduced and increased Pb uptake in low PbAc–ZnAc and high PbAc–ZnAc groups compared to PbAc only groups, respectively. Bone Pb levels in the high PbAc–ZnAc group were lower than the high PbAc group. Zinc co-administration attenuated Pb-induced inhibition of delta aminolaevulinic acid dehydratase enzyme and enhanced catalase enzyme activity at a high level of exposure. Moreover, ZnAc seems to have minimized the effects of Pb-induced mRNA dysregulation in antioxidant and antiapoptotic enzymes encoding genes. Heme oxygenase-1 was downregulated in the kidney and brain in the low PbAc group. Liver glutathione peroxidase and thioredoxin reductase-1 were downregulated in the high PbAc group. These findings suggest that zinc co-administration with lead may partially mitigate against Pb-induced toxicities.     

Spontaneous thymoma in a 10-week-old sprague-dawley rat

Spontaneous thymoma was found in the left lobe of the thymus of a male 10-week-old Sprague-Dawley (SD) rat. Microscopically, the thymic mass showed a sheet of dark area with multiple pale foci. The dark area mainly consisted of densely compacted small lymphoid cells with sporadic large epithelioid cells and mitotic figures. The epithelioid cells and mitotic figures were more frequent than those of the normal thymic cortex in this animal. The multiple pale foci were similar to the normal thymic medulla and occasionally had Hassall's corpuscles; thus, they were regarded as medullary differentiation areas. Furthermore, some perivascular spaces recognized as characteristics of thymoma were present in the center of the mass. Immunohistochemically, the epithelioid cells in the dark area were positive for cytokeratin. Ultrastructurally, desmosomes and tonofilaments were observed in the epithelioid cells. Thus, this tumor was diagnosed as a thymoma. This is a rare case of thymoma occurring spontaneously in young adult SD rat.     

Highly invasive intracranial malignant schwannoma in a rat

A highly invasive intracranial malignant schwannoma containing several masses was detected in a 28-week-old male Crl:CD(SD) rat. Macroscopically, 3 masses were noted in the cranial cavity; one was present at the bottom of the cranial cavity and involved the trigeminal nerve, and the other two were in the parietal bone. Histologically, each mass consisted of fusiform cells with interlacing fascicular, wavy and nuclear pseudopalisading arrangements and round cells with cystic lesions. The tumor cells invaded not only the brain but also the parietal bone. In the brain, the tumor cells infiltrated diffusely into the leptomeningeal and perivascular spaces and parenchyma, in which the tumor cell morphology and invasive pattern closely resembled those of malignant astrocytoma and malignant reticulosis. Immunohistochemically, the tumor cells in the masses showed positive reactions for both S-100 protein and GFAP, while those in the cerebral invasion sites were negative for GFAP and less positive for S-100 protein. Electron microscopically, a single basal lamina layer and short intricate cell processes were confirmed in the tumor cells. From these results, the present tumor was diagnosed as a malignant schwannoma arising in the cranial cavity, probably originating from the trigeminal nerve. The present tumor is considered to be a relatively unique malignant schwannoma based on its growth and invasion patterns.     

Postnatal development of metallophilic macrophages in the rat thymus

Metallophilic macrophages (MMs) are a distinct cell type of the rodent thymus. Our previous research has focused on the morphological characteristics of MMs, as well as on the molecular mechanisms involved in the development and tissue positioning of these cells. However, the postnatal development of MMs has not been sufficiently studied. In the present study, we investigated the positioning of MMs in the rat thymus between postnatal day 0 (P0) and P30. On P0, MMs were evenly distributed all over the thymic tissue—that is, the cortex, cortico-medullary zone and medulla. From P0 to P15, the number of MMs in the thymic cortex significantly decreased, and after P15, this number did not change. Thus, the present study shows that on P15, MMs almost completely disappear from the thymic cortex and show their adult position in the cortico-medullary zone and in the medulla.     

Spontaneous chondrosarcoma in Wistar rat: a case report

In rats, chondrosarcomas have been reported to occur both spontaneously and secondary to chemical induction. In a rare case, a spontaneous chondrosarcoma was identified in the deformed femur of a young male Wistar rat. After gross examination of the femur and knee joint, tissue was collected and preserved. The formalin-fixed tissue was decalcified, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. Microscopic examinations revealed a large, highly proliferative, noncapsulated growth of chondrocytic or chondroblastic origin in the femoral bone, with proliferating chondrocytes invading the bone and surrounding tissues in an infiltrative growth pattern. Based on its histomorphological features, the lesion was diagnosed as a malignant cartilaginous neoplasm of spontaneous origin.     

Highly metastatic ovarian yolk sac carcinoma in a rat

We investigated a highly metastatic ovarian yolk sac carcinoma in a 52-week-old female Crl:CD(SD) rat. Macroscopically, the present case had severe ascites, bilateral ovarian masses and numerous nodules in the abdominal and thoracic cavities. Histopathologically, these masses and nodules were generally composed of two types of cells mimicking a parietal and visceral yolk sac. The parietal cells were round to polygonal, contained eosinophilic droplets and were arranged in nests and cords in the eosinophilic matrix. Both the intracytoplasmic droplets and the matrix were stained positively with PAS. The visceral cells were cylindriform, and proliferated in papillary and tubular patterns and occasionally formed Shiller-Duval body-like structures. In the dissemination sites, the neoplastic cells proliferated on the surface of the various tissues and often infiltrated into deeper parts of the tissues. Immunohistochemically, both neoplastic cells were positive for α-fetoprotein and keratin, and the eosinophilic matrix was positive for laminin. Ultrastructurally, the parietal cells had dilated rough endoplasmic reticulums, which were filled with electron-lucent laminated structures. The visceral cells had poorly to moderately developed intracytoplasmic organelles and were interconnected with desmosomes. Taken together, the present tumor was diagnosed as yolk sac carcinoma arising from the ovary and was characterized by not only high metastasis but also invasive infiltration with biphasic proliferation of the parietal and visceral cells.     

Cervical thymoma originating in ectopic thymic tissue in a cat

Abstract: An 11‐year‐old female spayed domestic shorthair cat was referred to The Ohio State University Veterinary Teaching Hospital (OSU‐VTH) for evaluation of a 6 × 4 × 3.5 cm mass in the left midcervical region causing increased respiratory sounds and lateral deviation of the trachea. A fine needle aspirate of the mass was obtained before referral and the cytology results were compatible with a reactive lymph node. Immunocytochemistry showed increased numbers of CD3+ T lymphocytes and small numbers of CD20+ and CD79a+ medium to large lymphocytes. Differential diagnoses from the referral pathologist were T‐cell‐rich B‐cell lymphoma and feline Hodgkin's‐like lymphoma. A subsequent fine needle aspirate performed at the OSU‐VTH showed similar results. On flow cytometry the majority of cells were CD3+ T lymphocytes that were double positive for CD4 and CD8 (73%), compatible with either a double‐positive (CD4+CD8+) T‐cell lymphoma or lymphocytes from ectopic thymic tissue. The mass was surgically removed. Histopathology and immunohistochemistry of the mass revealed a predominant population of CD3+ small lymphocytes and small numbers of medium to large lymphocytes with moderate anisocytosis and anysokaryosis. A population of cytokeratin‐positive epithelial cells surrounded small microcystic structures filled with eosinophilic material and structures interpreted as Hassall's corpuscles. These findings were consistent with thymic tissue and a diagnosis of ectopic thymoma was made. PCR results for lymphocyte antigen receptor rearrangement (PARR) were negative. The cat had no evidence of disease 16 months after removal of the mass. To our knowledge this is the first report of an ectopic cervical thymoma in a cat. The clinical and diagnostic features of this unusual case will be useful in helping veterinarians and pathologists obtain a presurgical diagnosis and establish a prognosis for similar lesions.