Atrophic Tubules Research Articles

Effect of Tamoxifen Drug on Testes of Albino Male Rats

This study was conducted to evaluate the negative effects of Tamoxifen (TAM) on Testis tissues andspermatogenesis. Use for this purpose forty male of mature albino rats were divided into 4 equal groups, 3groups were administrated different doses (30, 40, 50) mg/kg b.w of TAM for 10 weeks as well as controlgroup administrated with physiological solution (normal saline 0.9%). Histopathological examination oftestes tissues in TAM groups showed histological changes that increased with the increased dose comparedto control group include degeneration change were appeared as atrophy, deformity and destruction of theseminiferous tubules, congestion of blood vessels in the interstitial tissue and many seminiferous tubules,Also the results showed a significant different in the numbers of spermatogonia, primary spermatocytescells and spermatiods. As noted in the results, the higher the dose, the lower the sperm production, andconsequently the tissue injury increases.

Pathomechanisms of Autoimmune Based Testicular Inflammation.

Infection and inflammation of the male reproductive tract are relevant causes of infertility. Inflammatory damage occurs in the special immunosuppressive microenvironment of the testis, a hallmark termed testicular immune privilege, which allows tolerance to neo-antigens from developing germ cells appearing at puberty, long after the establishment of systemic immune tolerance. Experimental autoimmune orchitis (EAO) is a well-established rodent model of chronic testicular inflammation and organ specific autoimmunity that offers a valuable in vivo tool to investigate the pathological and molecular mechanisms leading to the breakdown of the testicular immune privilege. The disease is characterized by the infiltration of the interstitium by immune cells (mainly macrophages, dendritic cells, and T cells), formation of autoantibodies against testicular antigens, production of pro-inflammatory mediators such as NO, MCP1, TNFα, IL6, or activins and dysregulation of steroidogenesis with reduced levels of serum testosterone. EAO leads to sloughing of germ cells, atrophic seminiferous tubules and fibrotic remodeling, parameters all found similarly to changes in human biopsies from infertile patients with inflammatory infiltrates. Interestingly, testosterone supplementation during the course of EAO leads to expansion of the regulatory T cell population and inhibition of disease development. Knowledge of EAO pathogenesis aims to contribute to a better understanding of human testicular autoimmune disease as an essential prerequisite for improved diagnosis and treatment.

Report of urinary bladder rupture following obstructive urolithiasis in rams of Romanov sheep flock

A 4-year old Romanov ram with a history of anorexia, severe depression, and anuria for 4 days was referred to the Veterinary Teaching Hospital of Lorestan University. In the clinical examinations of the ram, no penile protrusion from prepuce, pain, straining; decreased body temperature; and increased heart rate and respiration rate were observed. For further evaluation, the blood sample was taken, and ultrasound of the abdominal area and ultrasound-guided cystocentesis were performed. The results indicated dehydration; leukocytosis; increased serum urea, creatinine, magnesium, and cholesterol; and decreased serum calcium concentrations. The ultra-sonographic findings demonstrated that the bladder was swollen and full of urine, however, without rupture. Despite the treatment, the ram was culled after 5 days and necropsy for investigating macroscopic changes, and tissue sampling was done. Macroscopic examination indicated a fibrinopurulent layer around the right kidney, and jagged stones with various sizes and shapes in the kidney and urinary tract were observed. Microscopic results showed atrophy and degeneration of renal tubules, destruction of tubules and glomeruli, fibrosis of the kidney, and increase in the thickness of the bladder wall.

The novel role of resveratrol in attenuating cisplatin induced testicular toxicity in rats.

Objectives: To evaluate the anti-oxidative role of Resveratrol in Cisplatin-induced testicular toxicity in Albino Wistar rats. Study Design: Quasi-experimental study. Settings: Department of Physiology and Postgraduate Laboratory of ISRA University Hyderabad. Period: Six months from March to September 2019. Material & Methods: Twenty-four male albino Wistar rats were distributed equally into; Group-I (Control), Group-II (Cisplatin), Group-III (Cisplatin + Resveratrol). Difference in mean pre and post-experimental body weight was observed while analysis of oxidative markers, semen parameters, and histomorphology was carried out in all three groups. SPSS ver. 22 was used to analyze the data. Results: The mean body weight decreased from 241.7±8.5 gm to 196.50±9.34 gm and from 237±7.4 gm to 210.0 ± 6.50gm in groups II and III respectively. Statistically significant reduction in semen parameters (sperm count, motility and viability) was observed in Group-II compared with Group-C (p<0.05). Oxidative markers were also significantly depleted in Group-II in comparison to Group-C (p<0.05). Histologically, testicular structure was found to be intact in Group-I. Marked changes were observed in testicular histology of Group-II while Group-III displayed less testicular damage. Irregular, regressive and atrophic seminiferous tubules were seen in Group-II. Most seminiferous tubules having normal morphology were observed in Group-III while the number of atrophic and degenerative seminiferous tubules also decreased significantly. Conclusion: Resveratrol therapy is a potent protective regime showing promising results in cisplatin-induced testicular toxicity and oxidative stress.

Intratubular epithelial-mesenchymal transition and tubular atrophy after kidney injury in mice.

Tubular atrophy is a common pathological feature of kidney fibrosis. Although fibroblasts play a predominant role in tissue fibrosis, the role of repairing tubular epithelia in tubular atrophy is unclear. We demonstrated the essential role of focal adhesion kinase (FAK)-mediated intratubular epithelial-mesenchymal transition (EMT) in the pathogenesis of tubular atrophy after severe ischemia-reperfusion injury (IRI). Actively proliferating tubular epithelia undergoing intratubular EMT were noted in the acute phase of severe IRI, resulting in tubular atrophy in the chronic phase, reflecting failed tubular repair. Furthermore, FAK was phosphorylated in the tubular epithelia in the acute phase of severe IRI, and its inhibition ameliorated both tubular atrophy and interstitial fibrosis in the chronic phase after injury. In vivo clonal analysis of single-labeled proximal tubular epithelial cells after IRI using proximal tubule reporter mice revealed substantial clonal expansion after IRI, reflecting active epithelial proliferation during repair. The majority of these proliferating epithelia were located in atrophic and nonfunctional tubules, and FAK inhibition was sufficient to prevent tubular atrophy. In vitro, transforming growth factor-β induced FAK phosphorylation and an EMT phenotype, which was also prevented by FAK inhibition. In an in vitro tubular epithelia gel contraction assay, transforming growth factor-β treatment accelerated gel contraction, which was suppressed by FAK inhibition. In conclusion, injury-induced intratubular EMT is closely related to tubular atrophy in a FAK-dependent manner.

Four-week repeated dose oral toxicity study of KDS2010, a novel selective monoamine oxidase B inhibitor, in Sprague Dawley rats

Repeated dose oral toxicity and toxicokinetic of KDS2010, a new drug for Parkinson's disease, was investigated after 4-week repeated oral administration at 30, 50, 75, or 100 mg/kg/day in rats. Body weight and body weight gain decreased in rats of both sexes in the 75 and 100 mg/kg groups, and food consumption was reduced in male rats of the 75 and 100 mg/kg male groups. Histological alterations were observed in the kidney (urothelial hyperplasia, inflammatory cell infiltration in the renal pelvis, tubular vacuolation/degeneration, basophilic tubules, and hyaline droplets in the proximal tubules) of the 75 and 100 mg/kg male groups and the 50 and 100 mg/kg female groups. The 75 and 100 mg/kg male groups showed adverse effect in the testes (degeneration/exfoliation of germ cells, seminiferous tubules atrophy) and epididymis (cellular debris, oligospermia). These changes were partially recovered after a 2-week recovery period. However, basophilic tubules and hyaline droplets in the proximal tubules in the kidney and germ cell degeneration/exfoliation in the testis were not recovered. In toxicokinetics study, systemic exposure to KDS2010 increased proportionally in both sexes by in a dose -dependent manner. In addition, repeated administration for 4 weeks led to increased tendency of systemic exposure in both sexes compared with that in Day 1. In conclusion, KDS2010 was shown to target the kidney and testis with a no-observed-adverse-effect level of 50 and 30 mg/kg/day for males and females, respectively.

Lack of retinoid acid receptor-related orphan receptor alpha accelerates and melatonin supplementation prevents testicular aging.

The role of retinoid acid receptor-related orphan receptor alpha (RORα) on male reproductive functions during aging is unclear. Here, we analyze the morphological changes in the testis of both young and aged RORα-deficient mice, with and without melatonin supplementation. Young mutants showed vacuolation, degeneration and pyknosis of spermatogenic epithelium and Sertoli cells. Aged mutants showed atrophy of the seminiferous tubules and absence of mitotic spermatogenic cells. Absence of sperms in many tubules, loss of acrosomal cap, vacuolation and hypertrophy of Sertoli cells were detected in aged mice, with a significant reduction in the number of seminiferous tubules and a significant increase in the number of Leydig cells and telocytes. Repair in seminiferous tubules and interstitial tissues with enhancement of spermatogenesis was observed in melatonin-treated aged mice. Young mutants overexpressed VEGF that was weaker in aged animals and observed only in the spermatocytes, while melatonin increased VEGF expression in spermatocytes and spermatids. Caspase 3 increased in both young and aged mutant mice in all seminiferous tubules and interstitium; caspase 3 immunostaining in seminiferous tubules, however, showed a normal pattern of apoptosis with melatonin supplementation. The present study reports that age-dependent testicular changes in RORα mutant mice were recovered by melatonin treatment.

Investigation of protective effects of lithium borate on spermatogenesis and testes histopathology against cadmium-induced acute toxicity in rats

In this study, protective effects of lithium borate LTB on spermatogenesis as well as histopathological and immunohistochemical findings of testes in experimentally induced acute Cadmium Cd toxicity in rats were determined. Twenty-eight male Wistar albino rats, were used, weighing 200-220 g. Rats were randomly divided into 4 groups: Control, Cd, LTB, and LTB + Cd. Rats were anesthetized with ketamine at the end of the sixth day, blood was taken from their hearts, and the rats were decapitated. Typically, the control and LTB groups exhibited similar values. Compared with those observed for the control group, the sperm morphology i.e. abnormal sperm count increased for the Cd group, while the FSH, LH, total testosterone levels, sperm motility, and density decreased in a statistically significant manner. Clearly, no adverse effects of LTB on the sperm motility, density, and sperm morphology i.e. abnormal sperm count were observed, but LTB decreased the negative effects of Cd toxicity. Abnormal disturbances in the head and tail areas of the sperms increased; thus, the total abnormal sperm rate increases, leading to the decreased fertilization capacity. The histopathological examination of testicular tissues revealed severe haemorrhage and hyperaemia in intertubular intervals, tubule atrophy, severe degenerative and necrotic changes in spermatocytes, tubule wall thinning, and necrosis in basal germ cells. In immunohistochemically Caspase-3, 8-OHdG, and COX-2 staining, changes in the control and LTB groups were not detected, while the Cd toxicity group exhibited severe expression in the testis tissue. Histopathological and immunohistochemical changes were significantly decreased in the LTB + Cd group compared to the Cd group. In conclusion, in this study it was determined that LTB has protective effects on Cd-induced testicular toxicity in rats.

Methyl parathion causes genetic damage in sperm and disrupts the permeability of the blood-testis barrier by an oxidant mechanism in mice

Methyl parathion (Me-Pa) is an extremely toxic organophosphorus pesticide still used in developing countries. It has been associated with decreased sperm function and fertility and with oxidative and DNA damage. The blood-testis barrier (BTB) is a structure formed by tight junction (TJ) proteins in Sertoli cells and has a critical role in spermatogenesis. We assessed the effect of repeated doses of Me-Pa (3−12 mg/kg/day for 5 days, i.p.) on sperm quality, lipid oxidation, DNA integrity, and BTB permeability in adult male mice and explored oxidation as a mechanism of toxicity. Me-Pa caused dose-dependent effects on sperm quality, lipoperoxidation, and DNA integrity. Testis histology results showed the disruption of spermatogenesis progression and atrophy of seminiferous tubules. The pesticide opened the BTB, as evidenced by the presence of a biotin tracer in the adluminal compartment of the seminiferous tubules. This effect was not observed after 45 days of exposure when a spermatogenic cycle had completed. The coadministration of the antioxidant α-tocopherol (50 mg/kg/day for 5 days, oral) prevented the effects of Me-Pa on sperm quality, DNA and the BTB, indicating the importance of oxidative stress in the damage generated by Me-Pa. As evidenced by immunochemistry, no changes were found in the localization of the TJ proteins of the BTB, although oxidation (carbonylation) of total proteins in testis homogenates was detected. Our results show that Me-Pa disturbs the BTB and that oxidation is involved in the observed toxic effects on sperm cells.

Characterization and distribution of sialic acids in human testicular seminoma

Aberrant content of sialic acids (Sias) has been observed in various human cancer types in different organs. Sias have been implicated in cancerous transformation, invasiveness and metastasis, and in the escaping of cancer cells from immune surveillance. Indeed, Sias are commonly regarded as important biomarkers to distinguish cancer cells from their healthy counterparts. However, scarce and not exhaustive investigations have been performed on Sia content in testicular cancers and, in particular, in seminoma, one of the most common malignant testicular tumors. Hence, the aim of this study was to investigate the content and distribution of Sias with different glycosidic linkage, namely α2,3 and α2,6 galactose- or N-acetyl-galactosamine-linked Sias and polymeric Sia (polySia), in the germinal and stromal components of human testes affected by seminoma compared to normal testicular tissue. Structural changes in seminoma tissue were examined using hematoxylin-eosin staining. α2,3 and α2,6 linked Sias were evaluated by lectin histochemistry (Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA)), while confocal immunofluorescence was used for polySia detection. Histopathological findings in seminoma tissue included loss of seminiferous tubules replaced by clusters of uniform polygonal cells with a clear cytoplasm, bundles of fibrotic tissue, numerous microvessels and some atrophic tubules. The content of α2,3 and α2,6 linked Sias was lost in almost all seminoma components respect to normal tissue, with the exception of microvessels in which it was higher. On the contrary, polySia level was increased in all the seminoma components compared to normal testicular tissue. Our findings suggest that an aberrant content of different Sias might have important and differential roles in seminoma development and progression. In particular, polySia might be implicated in seminoma progression by promoting cancer invasiveness and regulating the cross-talk between cancer cells, reactive stroma and vessels. Thus, the possibility that polySia might represent an important biomarker for seminoma deserves further investigation.

Effect of Bleomycin, Etoposide, and Cisplatin Treatment on Spermatogonia Cell and Malondialdehyde Level in Male Rats

Co-administration of bleomycin, etoposide, and cisplatin (BEP) becomes standart chemotherapy for testicular cancer because it has brought a cure rate of more than 90%. Impact of the treatment to the outcome become a concern, particularly the adverse effect on a long-term reproductive health risk to cancer survivors. There is no evidence, when the damage to the testes began due to the administration of BEP chemotherapy, makes the indication of treatment still controversial. The aim of this study is to determine the effects of BEP on Spermatogonial cell and MDA levels outcome in an animal model. Male wistar rats (Rattus norvegicus) aged 13-15 weekswere treated daily with BEP for three cycles, 33 hours each. It was divided into one control group received 1cc of normal saline, and three groups received three cycles of 0.5 x dose-levels of BEP (Intraperitoneally; 0.75 mg/kg, 7.5 mg/kg, and 1.5 mg/kg). Cell number of Spermatogonia cells were calculated from HE-stained specimens and observed under light microscope (Olympus BX-51) using 400x magnification (high power field) Thiobarbituric acid (TBA) test method used to measure malondialdehyde (MDA) level by spectrophotometry. The result was a significant decrease in the average number of Spermatogonia cells (p = 0.003) between the control group and others. This is caused by excessive exposure to BEP chemotherapy, which cause atrophy of the seminiferous tubules and content of germ cells in the tubules has decreased, accompanied by the appearance of immature germ cells that enter the lumen. A significant increase in MDA levels (p = 0.001) occurred after the administration of the third cycle of BEP chemotherapy. In conclusion, BEP chemotherapy adversely affect the number of Spermatogonia cells and MDA level. The third cycle BEP chemotherapy significantly more destructive compared to the first and second cycle.

Evaluation of Renal Function in Obstructed Ureter Model Using 99mTc-DMSA.

Urinary obstruction is a condition of impaired urinary drainage, which may result in progressive renal deterioration. This study applied 99mTc-labeled dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy to a rabbit model of right ureter obstruction and evaluated its utility in studying obstructive renal diseases. Complete unilateral ureter obstruction in rabbits was generated by complete ligation of the right ureter. Renal function was investigated during a 4-week post-obstruction period by obtaining planar images of 99mTc-DMSA activity following ear vein injection. Renal blood perfusion was evaluated by non-invasive scintigraphy in conjunction with parallel histological and hematological examinations. Renal perfusion was remarkably and rapidly reduced in the ureter-obstructed kidneys. During the experimental period, the size of left kidney appeared normal in the scintigraphic images, but the ureter-obstructed right kidney progressively became larger. Histopathological examination showed flattening and atrophy of tubules, enlargement of interstitial areas, accumulation of extracellular martices and infiltration of inflammatory cells in the obstreucted kidney. 99mTc-DMSA scintigraphy is a sensitive, non-invasive method to assess renal function in unilateral kidney diseases.

Reno-protection of Urine-derived Stem Cells in A Chronic Kidney Disease Rat Model Induced by Renal Ischemia and Nephrotoxicity.

Purpose: Drug-induced nephrotoxicity can occur in patients with pre-existing renal dysfunction or renal ischemia, potentially leading to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Prompt treatment of CKD and the related side effects is critical in preventing progression to ESRD. The goal of this study was to demonstrate the therapeutic potential of urine-derived stem cells (USC) to treat chronic kidney disease-induced by nephrotoxic drugs and renal ischemia.Materials and methods: Human USC were collected, expanded and characterized by flow cytometry. A CKD model was induced by creating an ischemia-reperfusion injury and gentamicin administration. Twenty-eight adult immunodeficient rats were divided into three groups: PBS-treated group (n=9), USC-treated group (n=9), and sham group with age-matched control animals (n=10). Cell suspension of USC (5 x 106 / 100µl / kidney) or PBS was injected bilaterally into the renal parenchyma 9 weeks after CKD model creation. Renal function was evaluated by collection blood and urine samples to measure serum creatinine and glomerulus filtration rate. The kidneys were harvested 12 weeks after cell injection. Histologically, the extent of glomerulosclerosis and tubular atrophy, the amount of collagen deposition, interstitial fibrosis, inflammatory monocyte infiltration, and expression of transforming growth factor beta 1 (TGF-ß1), and superoxide dismutase 1 (SOD-1) were examined.Results: USC expressed renal parietal epithelial cells (CD24, CD29 and CD44). Renal function, measured by GFR and serum Cr in USC-treated group were significantly improved compared to PBS-treated animals (p<0.05). The degree of glomerular sclerosis and atrophic renal tubules, the amount of fibrosis, and monocyte infiltration significantly decreased in USC-treated group compared to the PBS group (p<0.05). The level of TGF-ß1 expression in renal tissues was also significantly lower in the PBS group, while the level of SOD-1 expression was significantly elevated in the USC group, compared to PBS group (p<0.05).Conclusions: The present study demonstrates the nephron-protective effect of USC on renal function via anti-inflammatory, anti-oxidative stress, and anti-fibrotic activity in a dual-injury CKD rat model. This provides an alternative treatment for CKD in certain clinical situations, such as instances where CKD is due to drug-induced nephrotoxicity and renal ischemia.

Evaluating the protective effect of resveratrol, Q10, and alpha-lipoic acid on radiation-induced mice spermatogenesis injury: A histopathological study.

BackgroundTestis is one of the most sensitive organs against the toxic effect of ionizing radiation. Exposure to even a low dose of radiation during radiotherapy, diagnostic radiology, or a radiological event could pose a threat to spermatogenesis. This may lead to temporary or permanent infertility or even transfer of genomic instability to the next generations.Objective In this study, we evaluated the protective effect of treatment with three natural antioxidants; resveratrol, alpha lipoic acid, and coenzyme Q10 on radiation-induced spermatogenesis injury.Materials and Methods30 NMRI mice (6-8 wk, 30 5 gr) were randomly divided into six groups (n = 5/each) as 1) control; 2) radiation; 3) radiation + resveratrol; 4) radiation + alpha lipoic acid; 5) radiation + resveratrol + alpha lipoic acid; and 6) radiation+ Q10. Mice were treated with 100 mg/kg resveratrol or 200 mg/kg alpha lipoic acid or a combination of these drugs. Also, Q10 was administered at 200 mg/kg. All treatments were performed daily from two days before to 30 min before irradiation. Afterward, mice were exposed to 2 Gy Co gamma rays; 37 days after irradiation, the testicular samples were collected and evaluated for histopathological parameters.Results Results showed that these agents are able to alleviate some toxicological parameters such as basal lamina and epididymis decreased sperm density. Also, all agents were able to increase Johnsen score. However, they could not protect against radiation-induced edema, atrophy of seminiferous tubules, and hyperplasia in Leydig cells.ConclusionThis study indicates that resveratrol, alpha-lipoic acid, and Q10 have the potential to reduce some of the side effects of radiation on mice spermatogenesis. However, they cannot protect Leydig cells as a source of testosterone and seminiferous tubules as the location of sperm maturation.

Protective role of glutamine against cadmium-induced testicular dysfunction in Wistar rats: Involvement of G6PD activity

BackgroundEndocrine disruptor such as cadmium has been widely reported to cause testicular toxicity, which contributes to recent decline in male fertility worldwide. Glutamine, the most abundant amino acid in the body has been demonstrated to exert protective effects in cellular toxicity. However, its role in testicular toxicity is unknown. The present study is therefore aimed at investigating the effects of glutamine supplementation on cadmium-induced testicular toxicity, and the possible involvement of glucose-6-phosphate dehydrogenase (G6PD) activity. Materials and methodMale Wistar rats weighing 160–190 g were allotted into 4 groups (n = 5/group): The groups received vehicle (distilled water; p.o.), glutamine (1gkg−1; p.o.), cadmium chloride (5mgkg−1p.o.) and Cadmium chloride plus glutamine respectively, daily for 30 days. Biochemical and histological analyses were performed with appropriate method. ResultsAdministration of cadmium significantly decreased body weight, sperm count, motility and viability, as well as altered sperm morphology and progressivity. Cadmium also caused atrophy of the seminiferous tubule in addition to disrupted testicular architecture, lumen, Sertoli cells and spermatogonia. Similarly, serum and testicular aspartate transaminase, and malondialdehyde significantly increased, and G6PD, glutathione, nicotinamide adenine dinucleotide phosphate and nitric oxide significantly decreased with corresponding decrease in follicle stimulating hormone, luteinizing hormone and testosterone in cadmium-treated animals compared with control groups. However, supplementation with glutamine attenuated these alterations. ConclusionThe present study demonstrates that cadmium induces testicular dysfunction that is attributable to defective G6PD and accompanied by increased lipid peroxidation and impaired NO-dependent endothelial function. Interestingly, glutamine supplementation ameliorates cadmium-induced testicular dysfunction through enhancement of G6PD activity.

Effect of electroacupuncture on renal fibrosis in spontaneously hypertension rats and its related mechanisms

To observe the effect of electroacupuncture (EA) on blood pressure, renal fibrosis and expression of tissue inhibitors of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor 1 (PAI-1), and alpha smooth muscle actin (α-SMA) in spontaneous hypertension rats (SHR), so as to explore its mechanisms underlying improving hypertensive renal damage. Forty male SHR (15 weeks in age) were randomly divided into 5 groups: model, medication (Losartan), Shenshu, Geshu, and Shenshu＋Geshu groups(n=8 rats in each group), and the same age-old male 8 Wistar-Kyoto (WKY) rats were used as the normal control group. Rats of the medication group were treated by gavage of Losartan potassium solution (3 mg/mL, 30 mg·kg-1·d-1, once a day for 12 weeks), and those of the 3 EA groups treated by EA stimulation of bilateral "Shenshu" (BL23), "Geshu"(BL17) or both BL23 and BL17 (2 Hz/100 Hz, 1 mA, 15 min each time, once every other day for 12 weeks). The systolic blood pressure of the tail artery was measured before, and 4, 8 and 12 weeks after the intervention. The expression of TIMP-1, PAI-1 and α-SMA proteins of the right kidney tissue was measured by immunohistochemistry. Histopathological changes of the right renal tissue were observed under light microscope after H.E. stain. The blood pressure was significantly higher in the mo-del group than those in the normal control group (P<0.01), and considerably decreased at the 4th , 8th, and 12th week of the interventions in the medication and 3 EA groups (P<0.01). The expression levels of renal TIMP-1, PAI-1 and α-SMA proteins were notably higher in the model group than those in the normal control group and considerably decreased at the 12th week of the interventions in the medication and 3 EA groups than in the model group (P<0.01). H.E. staining of the renal tissue showed disordered arrangement of the renal cells, congestion and dilation of capillaries with thickened vascular wall, renal tubule atrophy and lumen stenosis with some necrosis of renal tubules, protein tubule and cell tubules, increase of some glomerular mesangial matrix and hyperplasia of fibrous tissue in the model group, which was re-latively milder in the medication and 3 EA groups. EA of BL23 and BL17 can reduce the blood pressure in SHR, which may be related to its function in down-regulating expression of TIMP-1, PAI-1 and α-SMA proteins.

Transplantation of adipose-derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model.

Aims/IntroductionAdipose‐derived mesenchymal stem cell (ASC) transplantation is a promising therapy for diabetic nephropathy (DN). However, intravascular administration of ASCs is associated with low engraftment in target organs. Therefore, we considered applying the cell sheet technology to ASCs. In this study, ASC sheets were directly transplanted into the kidneys of a DN rat model, and therapeutic consequences were analyzed.Materials and MethodsAdipose‐derived mesenchymal stem cells were isolated from adipose tissues of 7‐week‐old enhanced green fluorescent protein rats, and ASC sheets were prepared using a temperature‐responsive culture dish. A DN rat model was established from 5‐week‐old Spontaneously Diabetic Torii fatty rats. Seven‐week‐old DN rats (n = 21) were assigned to one of the following groups: sham‐operated (n = 6); ASC suspension (6.0 × 106 cells/mL) administered intravenously (n = 7); six ASC sheets transplanted directly into the kidney (n = 8). The therapeutic effect of the cell sheets was determined based on urinary biomarker expression and histological analyses.ResultsThe ASC sheets survived under the kidney capsule of the DN rat model for 14 days after transplantation. Furthermore, albuminuria and urinary tumor necrosis factor‐α levels were significantly lower in the ASC sheets transplanted directly into the kidney group than in the sham‐operated and ASC suspension administered intravenously groups (P < 0.05). Histologically, the ASC sheets transplanted directly into the kidney group presented mild atrophy of the proximal tubule and maintained the renal tubular structure.ConclusionsTransplantation of ASC sheets directly into the kidney improved transplantation efficiency and suppressed renal injury progression. Therefore, the ASC sheet technology might be a promising novel treatment for DN.

Dietary soybean oil, canola oil and partially-hydrogenated soybean oil affect testicular tissue and steroid hormone levels differently in the miniature pig

The present study was conducted to examine the influence of dietary canola oil (CAN) and partially-hydrogenated soybean oil (HSO) compared to soybean oil (SOY, control) on the morphology and function of testes using miniature pigs as the test subject. Male miniature pigs were fed a diet containing 10%SOY, 9%CAN+1%SOY, or 9%HSO+1%SOY for 18 months. The scheduled autopsies revealed no abnormalities in histopathological examination of the major organs, except the testes. Atrophy of the seminiferous tubules and hyperplasia in the Leydig cells were found in the SOY and CAN groups. DNA microarray analysis indicated downregulation in the CAN and the HSO groups of genes encoding for gonadotropins in the pituitary gland and of enzymes and proteins involved in steroid hormone metabolism in the testes, compared to the SOY group. Plasma levels of sex hormones in the CAN and HSO groups tended to be higher and testosterone and dihydrotestosteorne in the HSO group were significantly higher than in the SOY group. These results demonstrate that testes are morphologically and functionally affected by the dietary oils, while the plasma steroid hormone levels do not necessarily reflect the gene expression, probably owing to feedback regulation via the gonadal hormones in the hypothalamus-pituitary-gonadal axis.

A comparison of parasites, pathological conditions and condition index of wild and farmed populations of Magallana bilineata (Roding, 1798) from Vembanad Lake, west coast of India

This study forms the first attempt to assess the health status, studying parasites and pathologies in wild or natural and farmed or cultured populations of the Indian backwater oyster, Magallana bilineata (= Crassostrea madrasensis Preston, 1916), the mainstay of oyster farming in the country. The Condition index, prevalence of infection, intensity, and seasonal variations in parasites and pathological conditions were studied. Wild oyster population was infected/infested with protozoan (Perkinsus beihaiensis, Nematopsis sp., Sphenophrya sp., and Stegotricha sp.), metazoan (cestodes and crustaceans), and shell (Polydora spp. and Cliona spp.) parasites and pathological conditions (digestive tubule atrophy, ceroid bodies, haemocytic infiltration, tissue necrosis, neoplastic disorders, and prokaryotic inclusions). Farmed population exhibited only a single protozoan (P. beihaiensis), a metazoan (Polydora sp.) infection and two pathological conditions (digestive tubule atrophy and ceroid bodies) in the tissues. The occurrence, prevalence and intensity rates for parasites and pathological conditions were significantly lower in farmed population compared to the wild population at the study site. Prevalence for parasites and pathologies were observed to be higher during dry season. The condition index (CI) values, which indicate the general health status of the oysters, were also significantly higher for the farmed population. The exposure period and the location of oysters in the habitat had a significant influence on the condition index and parasitic load in the population. None of the parasites were OIE listed; however the presence of a potential pathogen (P. beihaiensis) and pathological conditions warrants regular monitoring of the stocks and water quality at the culture site.

Prenatal exposures to bisphenol A and di (2-ethylhexyl) phthalate disrupted seminiferous tubular development in growing male rats

Endocrine-disrupting compounds (EDCs) are found in the environment due to their use in industrial and manufacturing activities. Exposure of the population to bisphenol A (BPA) and di (2-ethylhexyl) phthalate (DEHP) is significant because they are present in many consumer products. EDCs target the reproductive tract because they express high levels of steroid hormone receptors, which act as transcriptional factors to regulate reproductive development. In the present study, timed-pregnant Long-Evans female rats (n = 8–10) were administered BPA and DEHP by oral gavage at 2.5 or 25 μg/kg body weight and 5 or 50 μg/kg body weight, respectively. Exposures to chemicals were limited to the period between gestational days 12 and 21 followed by assessment of testicular development in male offspring in the postnatal period. Leydig cells and Sertoli cells are the two major somatic cells present in the testis. The 17β-hydroxysteroid dehydrogenase (17β-HSD) steroidogenic enzyme is a marker for Leydig cell maturation, whereas transferrin is a marker for Sertoli cell differentiation. At day 10 post-partum, testes were obtained from cohorts of control and chemical-exposed male rats and processed to measure 17β-HSD and transferrin expression levels in western blots. Compared to control, 17βHSD enzyme protein was increased in BPA-treated rats but levels were decreased in animals exposed to DEHP (P < 0.05). Transferrin protein was decreased in male rats exposed to both BPA and DEHP compared to control animals (P < 0.05). To assess qualitative cellular changes within the spermatogenic epithelium, testes were obtained from separate cohorts of male rats at 35 days of age and processed for histopathological analysis. Results showed that prenatal exposures of male rats to BPA and DEHP caused disruption of the spermatogenic epithelium evident as disorganization and atrophy of seminiferous tubules as well as desquamation of germ cells into the tubular lumen. Together, results from the present study support the view that developmental exposures to environmentally relevant levels of BPA and DEHP are associated with disruptions of testicular cell development, which have implications for endocrine and exocrine functions of testis.