Systemic autoimmune abnormalities alter the morphology of mucosa-associated lymphoid tissues in the rectum of MRL/MpJ-Faslpr/lpr mice.

Systemic autoimmune diseases (ADs) might affect the morphology and function of gut-associated lymphoid tissue (LTs) indirectly; however, their exact relationship remains unclear. Therefore, we investigated mouse LTs in the anorectal canal and morphologically compared them between MRL/MpJ-Fas+/+ and MRL/MpJ-Faslpr/lpr mice. LT aggregations, also known as rectal mucosa-associated lymphoid tissues (RMALTs), were exclusively seen in the lamina propria and submucosa of the rectum. The mean size and number of the LT aggregations both significantly increased in MRL/MpJ-Faslpr/lpr mice compared to those in MRL/MpJ-Fas+/+ mice. The distance from the anorectal junction to the first LT aggregate was significantly shorter in MRL/MpJ-Faslpr/lpr mice than that in MRL/MpJ-Fas+/+ mice. Immunostaining revealed that the RMALTs included CD3+, CD4+, and CD8+ T cells; B220+ B cells; IBA1+ macrophages; Ki67+ proliferative cells; and PNAd+ high-endothelial venules (HEVs). The numbers of macrophages, proliferative cells, CD4+ T cells, CD8+ T cells, and HEVs were significantly increased in MRL/MpJ-Faslpr/lpr mice compared to those in MRL/MpJ mice. Furthermore, the gene expression levels of chemokines (Cxcl9 and Cxcl13) and their corresponding receptors (Cxcr3 and Cxcr5) were significantly higher in MRL/MpJ-Faslpr/lpr mice than those in MRL/MpJ-Fas+/+ mice. Although the morphology of rectal epithelium was comparable between the strains, M cell number was significantly higher in MRL/MpJ-Faslpr/lpr mice than in MRL/MpJ-Fas+/+ mice. Thus, ADs could alter RMALT morphology, and quantitative changes in T-cell subsets, proliferative cells, macrophages, HEVs, chemokine expression, and M cells could affect their cell composition and development.

Effects of glucose and trehalose on tris-citric acid-egg yolk-fructose diluents for semen cryopreservation in goat.

Objectives: This study aimed to examine the impacts of the wide range of concentrations of glucose and trehalose on the tris-citric acid-egg yolk-fructose (TCEF) extenders for cryopreservation of goat semen. Materials and Methods: The sperm sample was pooled, washed, and diluted in control (TCEF without glucose and trehalose), TCEF + glucose (75, 150, 450, and 900 mm), and TCEF + trehalose (75, 150, 450, and 900 mm). After equilibrations, the semen straws were frozen under LN2 in the LN2 tank. After LN2 storage, the straws were thawed at 37°C for 30 seconds. The sperm parameters of all study groups were checked after equilibration and freezing. Results: After equilibration, the progressive motility (PM), total motility (TM), and viability of sperm in G-75, G-150, G-450, T-75, T-150, and T-450 were not significantly different (p < 0.05) from those in control. After cryopreservation and thawing, the PM, TM, and plasma membrane integrity (PMI) of T-150 were significantly higher (p < 0.05) than in control, G-75, G-900, T-75, and T-900. The viability of sperm in T-150 was substantially higher (p < 0.05) than in the control, whereas there was no significant difference among the control, G-75, G-900, T-75, and T-900. However, the acrosome integrity (AI) of sperm in G-900 was significantly decreased (p < 0.05) compared to the control, G-75, G-150, G-450, T-75, T-150, and T-450. Conclusion: According to the findings, the supplementation of 150 mm trehalose in the TCEF diluent was more efficient for sperm cryopreservation in the buck as reflected by PM, TM, viability, PMI, and AI.

Morphological Characteristics of Genital Organ-Associated Lymphoid Tissue in the Vaginal Vestibule of Goats and Pigs.

Mucosa-associated lymphoid tissue (MALT) is a specialized form of peripheral lymphoid tissue (LT), which is found on mucosal surfaces exposed to the environment. However, morphological data of these tissues in farm animals are scarce. This study investigated the gross anatomical and histological features of genital organ-associated lymphoid tissues (GOALTs) in the vaginal vestibule (VV) of healthy, non-pregnant, adult goats and pigs. Their VVs were composed of stratified squamous, non-keratinized epithelium, and various-sized dark-blue hematoxylin-positive spots were observed in whole-mount specimens, which were diffusely distributed throughout the mucosal surfaces. These spots were histologically identified as LTs and consisted of lymphatic nodules (LNs) or diffuse lymphoid tissue (DLTs). Both LNs and DLTs contained B cells, T cells, macrophages, dendritic cells, plasma cells, and high endothelial venules. Only the numbers of B cells were significantly higher in both the LNs and DLTs of pigs compared to goats. Furthermore, the surface of the VV epithelium covering the LTs was partially disrupted with a large intercellular space containing abundant connective tissue fibers with numerous lymphocytes. In conclusion, GOALTs in the VV appear to be common local immunological barriers in both examined animals. This knowledge is crucial for understanding the structures and disorders of female reproductive organs in farm animals.

Expression of Indian hedgehog signaling in murine oviductal infundibulum and its relationship with epithelial homeostasis.

Homeostasis of the oviductal infundibulum epithelium is continuously regulated by signaling pathways under physiological and pathological conditions. Herein, we investigated the expression of hedgehog (Hh) signaling-related components in the murine oviductal infundibulum, which is known to maintain homeostasis in the adult epithelium. Additionally, using autoimmune disease-prone MRL/MpJ-Faslpr/lpr (MRL/lpr) mice showing abnormal morphofunction of the ciliated epithelium of the infundibulum related to the oviductal inflammation, we examined the relationship between Hh signaling and pathology of the infundibulum. The expression and localization of Pax8, a marker for progenitor cells in the oviductal epithelium, and Foxj1, a marker for ciliogenesis, were examined in the infundibulum. The results showed that Pax8 was downregulated and Foxj1 was upregulated with aging, suggesting that homeostasis of the infundibulum epithelium of MRL/lpr mice was disturbed at 6 months of age. In all mice, the motile cilia of ciliated epithelial cells in the infundibulum harbored Hh signaling pathway-related molecules: patched (Ptch), smoothened (Smo), and epithelial cells harbor Gli. In contrast, Ptch, Smo, and Gli2 were significantly downregulated in the infundibulum of MRL/lpr mice at 6 months of age. The expression levels of Pax8 and Foxj1 were significantly positively correlated with those of Ptch1, Smo, and Gli2. Hh signaling is thought to be involved in homeostasis of the ciliated epithelium in the infundibulum. In MRL/lpr mice, which show exacerbated severe systemic autoimmune abnormalities, molecular alterations in Hh signaling-related components are considered to interact with local inflammation in the infundibulum, leading to disturbances in epithelial homeostasis and reproductive function.

Modified foreign body reaction to silicone imbedded in subcutaneous tissues by different mouse systemic immune conditions.

Foreign body reaction (FBR) causes unexpected adverse effects due to implanted materials in humans and animals. Inflammation and subsequent fibrosis during FBR seems to be affected by recipient immunity, such as the balance of T helper (Th) response that has the potential to regulate FBR-related macrophage function. Here, the immunological effects of FBR on subcutaneously imbedded silicone tubes (ST) at 8 weeks were investigated histologically by comparing Th1-biased C57BL/6N, Th2-biased MRL/MpJ, and autoimmune disease-prone MRL/MpJ-Faslpr/lpr . Tissue surrounding ST (TSS) was analyzed at day (D) 7 and 14 (reaction phase) or D35 (stability phase) after surgery. In all strains, the TSS was composed of a thin layer (TL) containing fibrous tissues and loose connective tissues formed outside the TL. Few lymphocytes and mast cells, several neutrophils, and numerous macrophages infiltrated the TSS. Active vascularization was observed at D14 in all strains. For the examined indices, M1-type macrophage density in the TSS of C57BL/6N mice was significantly higher at D14 compared to other strains. No significant strain difference relating to M2-type macrophages was detected, suggesting the effects of Th1-biased immunity on FBR-related inflammation. Collagen fibers in the TSS increased in density and became stable with age in all strains. In particular, MRL/MpJ-Faslpr/lpr showed progressive fibrotic features. Serum autoantibody levels in MRL/MpJ-Faslpr/lpr mice were inversely correlated with M1-type macrophage density. These data from MRL/MpJ-Faslpr/lpr mice suggested modifications of FBR-related inflammation and fibrosis by autoimmune abnormalities. The results provide crucial insights into the pathological modification of FBR by recipient immunity and emphasize its clinicopathological importance in humans and animals.

The Ameliorative Effect of Dexamethasone on the Development of Autoimmune Lung Injury and Mediastinal Fat-Associated Lymphoid Clusters in an Autoimmune Disease Mouse Model.

In our previous study, we revealed the ameliorative therapeutic effect of dexamethasone (Dex) for Lupus nephritis lesions in the MRL/MpJ-Fas lpr/lpr (Lpr) mouse model. The female Lpr mice developed a greater number of mediastinal fat-associated lymphoid clusters (MFALCs) and inflammatory lung lesions compared to the male mice. However, the effect of Dex, an immunosuppressive drug, on both lung lesions and the development of MFALCs in Lpr mice has not been identified yet. Therefore, in this study, we compared the development of lung lesions and MFALCs in female Lpr mice that received either saline (saline group "SG") or dexamethasone (dexamethasone group "DG") in drinking water as a daily dose along with weekly intraperitoneal injections for 10 weeks. Compared to the SG group, the DG group showed a significant reduction in the levels of serum anti-dsDNA antibodies, the size of MFALCs, the degree of lung injury, the area of high endothelial venules (HEVs), and the number of proliferating and immune cells in both MFALCs and the lungs. A significant positive correlation was observed between the size of MFALCs and the cellular aggregation in the lungs of Lpr mice. Therefore, this study confirmed the ameliorative effect of Dex on the development of lung injury and MFALCs via their regressive effect on both immune cells' proliferative activity and the development of HEVs. Furthermore, the reprogramming of MFALCs by targeting immune cells and HEVs may provide a therapeutic strategy for autoimmune-disease-associated lung injury.

Scanning electron microscopy of Quilonia renniei from Asian elephants revealing variation in coronal leaflet number.

Although parasitic nematodes in the genera Murshidia and Quilonia (family Strongylidae) are recognized as major gastrointestinal parasites in Asian elephants, they have been poorly studied. Recently, light micrographs of these parasites in Myanmar have been presented, almost 100 years after the original drawings. However, the number of coronal leaflets, a key taxonomic feature of Quilonia species, has not been precisely determined based on light microscopy. The current study aimed to determine the exact number of coronal leaflets in Quilonia renniei specimens from Asian elephants in Myanmar. On the basis of scanning electron micrographs, leaflet number in females (19­20, average 19.7, n = 9) was significantly higher (P < 0.005) than that in males (16­19, average 18.1, n = 8). This compares with 18 coronal leaflets indicated in the original species description. Specimens bearing 19 coronal leaflets were most numerous, followed by those with 20 leaflets. Median-joining network analysis of mitochondrial cytochrome c oxidase subunit I gene sequences with 16 haplotypes from 19 individuals revealed no clear association between parasite populations and the number of coronal leaflets. These results highlight the importance of determining the number of coronal leaflets in the taxonomy of Q. renniei and other related Quilonia species infecting Asian elephants.

Genital organ-associated lymphoid tissues arranged in a ring in the mucosa of cow vaginal vestibules.

Female reproductive tracts are equipped with local and mucosal immune systems; however, structural information remains unclear for farm animals. In this study, the mucosa-associated lymphoid tissue-like structures in cow reproductive tracts were described. Vaginal vestibule (VV) and external parts of the genital organ, including the clitoris and vulva, were morphologically analyzed. Whole-mount specimens revealed several hematoxylin-positive spots arranged in a ring in the mucosa. Histologically, these spots were aggregated immune cells and defined as genital organ-associated lymphoid tissues (GOALTs). GOALTs were composed of lymphatic follicles (LFs) or diffuse lymphoid tissues (DLTs) at different depths of lamina propria. LFs frequently contained germinal centers. Scattered lymphocytes occupied the border area between follicles and epithelium, whereas DLTs had indefinite shapes. GOALTs contained immune cells and high endothelial venules. B cells were dominant both in LFs and DLTs. Abundant collagenous fibers were stretched across VV lamina propria, whereas reticular fibers were primarily observed in the DLT rather than LF. The epithelium covering of GOALTs was partially or fully disrupted by the invasion of immune cells toward the VV lumen. These findings suggest GOALTs function as a "genital lymphoid ring" as in Waldeyer's pharyngeal ring and act as immunological gate systems in cow reproductive tracts.

Close Association between Altered Urine-Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during Nephritis.

BACKGROUND: Kidneys with chronic inflammation develop tertiary lymphoid structures (TLSs). Infectious pyelonephritis is characterized by renal pelvis (RP) inflammation. However, the pathologic features of TLSs, including their formation and association with non-infectious nephritis, are unclear. METHODS: RPs from humans and mice that were healthy or had non-infectious chronic nephritis were analyzed for TLS development, and the mechanism of TLS formation investigated using urothelium or lymphoid structure cultures. RESULTS: Regardless of infection, TLSs in the RP, termed urinary tract-associated lymphoid structures (UTALSs), formed in humans and mice with chronic nephritis. Moreover, urine played a unique role in UTALS formation. Specifically, we identified urinary IFN-γ as a candidate factor affecting urothelial barrier integrity because it alters occludin expression. In a nephritis mouse model, urine leaked from the lumen of the RP into the parenchyma. In addition, urine immunologically stimulated UTALS-forming cells via cytokine (IFN-γ, TNF-α) and chemokine (CXCL9, CXCL13) production. CXCL9 and CXCL13 were expressed in UTALS stromal cells and urine stimulation specifically induced CXCL13 in cultured fibroblasts. Characteristically, type XVII collagen (BP180), a candidate autoantigen of bullous pemphigoid, was ectopically localized in the urothelium covering UTALSs and associated with UTALS development by stimulating CXCL9 or IL-22 induction via the TNF-α/FOS/JUN pathway. Notably, UTALS development indices were positively correlated with chronic nephritis development. CONCLUSIONS: TLS formation in the RP is possible and altered urine-urothelium barrier-based UTALS formation may represent a novel mechanism underlying the pathogenesis of chronic nephritis, regardless of urinary tract infection.

Abnormal Blood Coagulation and Kidney Damage in Aged Hamsters Infected with Severe Acute Respiratory Syndrome Coronavirus 2.

Systemic symptoms have often been observed in patients with coronavirus disease 2019 (COVID-19) in addition to pneumonia, however, the details are still unclear due to the lack of an appropriate animal model. In this study, we investigated and compared blood coagulation abnormalities and tissue damage between male Syrian hamsters of 9 (young) and over 36 (aged) weeks old after intranasal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite similar levels of viral replication and inflammatory responses in the lungs of both age groups, aged but not young hamsters showed significant prolongation of prothrombin time and prominent acute kidney damage. Moreover, aged hamsters demonstrated increased intravascular coagulation time-dependently in the lungs, suggesting that consumption of coagulation factors causes prothrombin time prolongation. Furthermore, proximal urinary tract damage and mesangial matrix expansion were observed in the kidneys of the aged hamsters at early and later disease stages, respectively. Given that the severity and mortality of COVID-19 are higher in elderly human patients, the effect of aging on pathogenesis needs to be understood and should be considered for the selection of animal models. We, thus, propose that the aged hamster is a good small animal model for COVID-19 research.

REV-ERB agonist suppresses IL-17 production in γδT cells and improves psoriatic dermatitis in a mouse model.

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperplasia and cellular infiltration. Studies have shown that disease development depends on proinflammatory cytokines, such as interleukin (IL)-23 and IL-17. It has been suggested that IL-23 produced by innate immune cells, such as macrophages, stimulates a subset of helper T cells to release IL-17, promoting neutrophil recruitment and keratinocyte proliferation. However, recent studies have revealed the crucial role of γδT cells in psoriasis pathogenesis as the primary source of dermal IL-17. The nuclear receptors REV-ERBs are ligand-dependent transcription factors recognized as circadian rhythm regulators. REV-ERBs negatively regulate IL-17-producing helper T cells, whereas the involvement of REV-ERBs in regulating IL-17-producing γδT (γδT17) cells remains unclear. Here we revealed the regulatory mechanism involving γδT17 cells through REV-ERBs. γδT17 cell levels were remarkably elevated in the secondary lymphoid organs of mice that lacked an isoform of REV-ERBs. A synthetic REV-ERB agonist, SR9009, suppressed γδT17 cells in vitro and in vivo. Topical application of SR9009 to the skin reduced the inflammatory symptoms of psoriasiform dermatitis in mice. The results of this study provide a novel therapeutic approach for psoriasis targeting REV-ERBs in γδT17 cells.

Morphological Features of the Testis among Autoimmune Mouse Model and Healthy Strains.

Autoimmune diseases play a critical role in the progression of infertility in both sexes and their severity has been reported to increase with age. However, few reports have discussed their effect on the morphological features of the testis. Therefore, we compared the morphological alterations in the testes of autoimmune model mice (MRL/MpJ-Faslpr) and the control strain (MRL/MpJ) with those of their background strain (C57BL/6N) at 3 and 6 months. Furthermore, we analyzed the changes in spermatocytes, Sertoli cells, immune cells, and Zonula occludens-1 junctional protein by immunohistochemical staining. The MRL/MpJ-Faslpr mice showed a significant increase in the serum Anti-double stranded DNA antibody level, relative spleen weight, and seminiferous luminal area when compared with other studied two strains. In contrast, a significant decrease in the relative testis weight, and numbers of both Sertoli, meiotic spermatocyte was observed in MRL/MpJ-Faslpr and MRL/MpJ mice compared with C57BL/6N mice especially at 6 months. Similarly, Zonula occludens-1 junctional protein positive cells showed a significant decrease in the same strains at 6 months. However, no immune cell infiltration could be observed among the studied three strains. Our findings suggest that the increase in autoimmune severity especially with age could lead to infertility through loss of spermatogenic and Sertoli cells, rather than the disturbance of the blood-testis barrier.

Compartmentalization of interleukin 36 subfamily according to inducible and constitutive expression in the kidneys of a murine autoimmune nephritis model.

The interleukin (IL) 36 subfamily belongs to the IL-1 family and is comprised of agonists (IL-36α, IL-36ß, IL-36γ) and antagonists (IL-36Ra, IL-38). We previously reported IL-36α overexpression in renal tubules of chronic nephritis mice. To understand the localization status and biological relationships among each member of the IL-36 subfamily in the kidneys, MRL/MpJ-Faslpr/lpr mice were investigated as autoimmune nephritis models using pathology-based techniques. MRL/MpJ-Faslpr/lpr mice exhibited disease onset from 3 months and severe nephritis at 6-7 months (early and late stages, respectively). Briefly, IL-36γ and IL-36Ra were constitutively expressed in murine kidneys, while the expression of IL-36α, IL-36ß, IL-36Ra, and IL-38 was induced in MRL/MpJ-Faslpr/lpr mice. IL-36α expression was significantly increased and localized to injured tubular epithelial cells (TECs). CD44+-activated parietal epithelial cells (PECs) also exhibited higher IL-36α-positive rates, particularly in males. IL-36ß and IL-38 are expressed in interstitial plasma cells. Quantitative indices for IL-36α and IL-38 positively correlated with nephritis severity. Similar to IL-36α, IL-36Ra localized to TECs and PECs at the late stage; however, MRL/MpJ-Faslpr/lpr and healthy MRL/MpJ mice possessed IL-36Ra+ smooth muscle cells in kidney arterial tunica media at both stages. IL-36γ was constitutively expressed in renal sympathetic axons regardless of strain and stage. IL-36 receptor gene was ubiquitously expressed in the kidneys and was induced proportional to disease severity. MRL/MpJ-Faslpr/lpr mice kidneys possessed significantly upregulated IL-36 downstream candidates, including NF-κB- or MAPK-pathway organizing molecules. Thus, the IL-36 subfamily contributes to homeostasis and inflammation in the kidneys, and especially, an IL-36α-dominant imbalance could strongly impact nephritis deterioration.

Comparison of Ovarian Morphology and Follicular Disturbances between Two Inbred Strains of Cotton Rats (Sigmodon hispidus).

Most mammalian ovarian follicles contain only a single oocyte having a single nucleus. However, two or more oocytes and nuclei are observed within one follicle and one oocyte, respectively, in several species, including cotton rat (CR, Sigmodon hispidus). The present study compared ovarian histology, focusing on folliculogenesis, between two inbred CR strains, HIS/Hiph and HIS/Mz. At 4 weeks of age, ovarian sections from both the strains were analyzed histologically. Multi-oocyte follicles (MOFs) and double-nucleated oocytes (DNOs) were observed in all stages of developing follicles in HIS/Hiph, whereas HIS/Mz had MOFs up to secondary stages and lacked DNOs. The estimated total follicles in HIS/Mz were almost half that of HIS/Hiph, but interstitial cells were well developed in HIS/Mz. Furthermore, immunostaining revealed no clear strain differences in the appearance of oocytes positive for Ki67, PCNA, and p63 in MOF or DNOs; no cell death was observed in these oocytes. Ultrastructural analysis revealed more abundant mitochondrial clouds in oocytes of HIS/Hiph than HIS/Mz. Thus, we clarified the strain differences in the CR ovary. These findings indicate that early events during folliculogenesis affect the unique ovarian phenotypes found in CRs, including MOFs or DNOs, and their strain differences.

Altered Renal Pathology in an Autoimmune Disease Mouse Model After Induction of Diabetes Mellitus.

Diabetes mellitus (DM) is a predisposing factor for renal disorder progression and is referred to as diabetic kidney disease (DKD). However, there are no reports of DKD with an underlying autoimmune disorder. In this study, we compared the pathophysiological changes caused by DM induction after streptozotocin (STZ) injection in comparison with that in a control group receiving citrate buffer (CB) in the autoimmune disease model mice "BXSB/MpJ-Yaa" (Yaa) and the wild-type strain BXSB/MpJ. Both strains showed hyperglycemia after 12 weeks of STZ injection. Interestingly, the Yaa group developed membranous and proliferative glomerulonephritis, which tended to be milder glomerular lesions in the STZ group than in the CB group, as indicated by a decreased mesangial area and ameliorated albuminuria. Statistically, the indices for hyperglycemia and autoimmune abnormalities were negatively and positively correlated with the histopathological parameters for mesangial matrix production and glomerular proliferative lesions, respectively. STZ treatment induced renal tubular anisonucleosis and dilations in both strains, and they were more severe in Yaa. Significantly decreased cellular infiltration was observed in the Yaa group compared to the CB group. Thus, in DKD related to autoimmune nephritis, hyperglycemia modifies its pathology by decreasing the mesangial area and interstitial inflammation and aggravating renal tubular injury.

Castrated autoimmune glomerulonephritis mouse model shows attenuated glomerular sclerosis with altered parietal epithelial cell phenotype.

Sex hormones help in maintaining proper immunity as well as renal homeostasis in mammals, and these multi-functional properties characterize the onset of sex-dependent diseases. To clarify the contribution of sex hormones to autoimmune disease-related renal pathogenesis, BXSB/MpJ-Yaa was investigated as a murine autoimmune glomerulonephritis model. BXSB/MpJ-Yaa and its wild-type, BXSB/MpJ-Yaa+ were castrated or sham-operated at three weeks and examined until six months of age. Both castrated strains showed significantly lower serum testosterone levels and body weights than sham-operated mice. Castration did not change the disease phenotypes in BXSB/MpJ-Yaa+. At three months, both sham-operated and castrated BXSB/MpJ-Yaa manifested splenomegaly, autoantibody production, and glomerulonephritis, and castrated BXSB/MpJ-Yaa tended to show heavier spleen weights than the sham-operated group. At six months, both the treated BXSB/MpJ-Yaa showed equivalent autoimmune disease conditions; however, castrated mice clearly showed milder glomerular sclerotic lesions than the sham-operated groups. Urinary albumin excretion in castrated BXSB/MpJ-Yaa was significantly milder than in sham-operated mice at four months, but those of both the treated BXSB/MpJ-Yaa were comparable at six months. The examined renal histopathological indices in parietal epithelial cells were remarkably altered by castration. Briefly, castration decreased the height of parietal epithelial cells and total parietal epithelial cell number in BXSB/MpJ-Yaa at six months. For immunostaining, parietal epithelial cells facing the injured glomeruli of BXSB/MpJ-Yaa expressed CD44, an activated parietal epithelial cell marker, and CD44-positive parietal epithelial cells showed nuclear localization of the androgen receptor and proliferation marker Ki67. CD44- or Ki67-positive parietal epithelial cells were significantly fewer in castrated group than in sham-operated BXSB/MpJ-Yaa at six months. Further, quantitative indices for CD44-positive parietal epithelial cell number and frequency in renal corpuscles positively correlated with glomerular sclerotic severity in BXSB/MpJ-Yaa. In conclusion, androgen seemed to have an effect on both systemic immunity and renal morpho-function; however, the effect on the latter could be more clearly observed in BXSB/MpJ-Yaa, as parietal epithelial cell activation resulted in glomerular sclerosis.

Spatiotemporal histological changes observed in mouse subcutaneous tissues during the foreign body reaction to silicone.

We investigated spatiotemporal changes in host tissues during foreign body reactions. Silicone tube was subcutaneously embedded into ICR mice, and tissue surrounding silicone (TSS) was observed at 2, 7, 14, 21, 28, 43, and 70 days (D) postsurgery. The thin layer (TL) and loose connective tissues (LCTs) (inside and outside the TSS) developed until D21 and densified afterward. Neutrophils infiltrated the TSS until D14 and formed neutrophil extracellular traps (NETs) in the TL during D7-21. In the LCTs, mast cell counts increased until D21, and macrophage numbers peaked at D14. Several macrophages showed LYVE-1 expression, supporting a tissue-remodeling role. Developmental indices of collagen fibers (CFs) and reticular fibers (RFs) increased during D2-21. NETs, but not neutrophils, were detected after D28. Mast cell numbers peaked at D43 and were maintained until D70. Myofibroblasts consistently localized to the TL from D14. During D21-28, the area of connective tissue (CNT), and CFs and RFs decreased and increased, respectively, and both remained constant during D28-70. The CF density remained constant from D21 and increased at D70. Thus, TSS showed two phases: inflammation and CNT development (D2-21), and inflammation convergence and CNT stabilization (D28-70). These results provide insights into foreign body reactions in clinical cases.

Unique Running Pattern and Mucosal Morphology Found in the Colon of Cotton Rats.

Cotton rats are one of the experimental rodents used for testing different infectious and non-infectious diseases, including gastrointestinal tract pathology. However, their intestinal morphological characteristics are still poorly understood. Here, we clarified the anatomical and histological characteristics of the cecum and ascending colon (AC) of young (1-3-month old), adult (4-6-month old), and old (10-12-month old) cotton rats. The large intestine (LI) in cotton rats is composed of the cecum, AC, transverse and descending colons, and rectum, and is similar to that of other mammals. The AC begins with a double or triple spiral loop-like flexure (SLLF) and ends with a coupled horseshoe-like flexure (HSLF). A single longitudinal mucosal fold (SLMF) was found at the beginning of the AC along the mesentery line and developed with age. Furthermore, the SLMF contained several lymphatic nodules (LNs), indicating their role in digestive and immunological functions. Small and large protuberant LNs were found in the cecum and SLLF, respectively, whereas thin and flat LNs were observed in the HSLF and transverse colon, respectively. Regarding sex-related differences, adult females had a significantly longer AC with a higher number of SLLFs compared to males. The SLMF length and LN number were also longer and higher, respectively, in adult females compared to adult males. These are crucial findings, indicating the presence of sex-related differences in the morphology of the LI in cotton rats, and ours is the first study to discover a sex difference in the mammalian LI lining. Our study clarified the unique morphology of the LI in cotton rats, which could serve as the principal model for elucidating species-specific digestive tract functions and gastrointestinal disorders.

Unique morphological characteristics in the ovary of cotton rat (Sigmodon hispidus).

Cotton rats (Sigmodon hispidus, CRs) are commonly used as animal models in biomedical research. However, the reproductive characteristics and ovarian development in the CRs has not been widely investigated. We have previously shown that female CRs, in particular, show several unique phenotypes associated with the urogenital system, such as chronic kidney disease and pyometra. Our investigation revealed unique morphologies in CR ovaries, particularly in oocytes. Cotton rat ovaries at 6-8 weeks of age were obtained from the Hokkaido Institute of Public Health, and their sections analyzed by light microscopy and transmission electron microscopy. Although the general histology and folliculogenesis of CR ovaries were similar to those of other experimental rodents, multi-oocyte follicles (MOFs) and double nucleated oocytes (DNOs) were also observed. Although MOFs were found at all stages of follicular development, a greater frequency of MOFs was observed in the primary and secondary stages. However, DNOs tended to be frequently observed in primordial follicles. Almost all MOF oocytes and a few DNOs possessed a clear zona pellucida, expressed DEAD (Asp-Glu-Ala-Asp) box polypeptide 4 and Forkhead box protein 2, a representative marker of oocytes and follicular epithelial cells. Thus, our investigations revealed the unique phenotypes of the CR ovary. As MOFs and DNOs are occasionally observed in human patients with infertility, the CR would be a useful animal model to study for gaining a better understanding of folliculogenesis and oocytogenesis, as well as their abnormalities in humans and other animals.

Histopathological changes in tear-secreting tissues and cornea in a mouse model of autoimmune disease.

IMPACT STATEMENT: Cornea, an outermost layer of mammalian eye, is protected by tear film and abnormalities of tear film causes dry eye. Dry eye injures the cornea which results lower vision in patients. Several factors cause dry eye, including altered systemic conditions, environment, and immunological abnormality of the patient in autoimmune disease like Sjögren's syndrome (SS). However, the detailed pathology of autoimmune abnormality-mediated dry eye is unclear. Here we demonstrated that systemic autoimmune abnormality in BXSB-Yaa mice was associated with histological changes in the exocrine glands and cornea of the eyes. We also showed that BXSB-Yaa mice developed mild or early stage dry eye-like disease and explain the existence of a compensatory mechanism associated with the dysfunction of these tissues. Thus, BXSB-Yaa could be a model for SS-like disease-associated dry eye and these data would contribute to the understanding of the pathogenesis of autoimmune-related dry eye disease.