scholarly journals Biochemical, thermographic, and follicular responses of murine models of hormone-treated bovine ovarian renal capsule xenografts

2017 ◽  
Vol 37 (5) ◽  
pp. 425-431 ◽  
Author(s):  
Muriel M.L. Pimentel ◽  
Fernanda A. Santos ◽  
Ana C.G. Teixeira ◽  
Roberta G. Izzo ◽  
Mikael A. Lima ◽  
...  

ABSTRACT: This study aimed to evaluate the characteristics of two different murine models of hormone-treated renal-encapsulated bovine ovarian tissue xenotransplantation. Two immunodeficient mouse models (BALB/c Nude and C57BL6 SCID) were xenografted with ovarian pieces from heifers and each group was subjected to two hormonal treatments of eCG or a combination of FSH+LH. Donor ovaries and recipients were evaluated by histology and infrared thermography at different times. At the time of xenograft collection, animals were evaluated for alterations in hepatorenal biochemistry. The statistical test used in the study was ANOVA, followed by Tukey’s test. Among the strains, 80% of C57BL6 SCID and 77% of BALB/c Nude mice showed development and vascularization of the transplanted tissue, which acquired cyclicity at 19 and 9 days post-transplant, respectively. Hemorrhagic follicles in xenografts induced with FSH+LH were found in the C57BL6 SCID strain. Infrared thermography was insufficient to distinguish the tissue donor recipient. In conclusion, the C57BL6 SCID strain appears to be the best host for ovarian xenografts, since the transplants in these mice were viable and showed robust follicular development. This work will aid future choices of immunodeficient strains for xenografting procedures.

2012 ◽  
Vol 24 (3) ◽  
pp. 461 ◽  
Author(s):  
L. Commin ◽  
S. Buff ◽  
E. Rosset ◽  
C. Galet ◽  
A. Allard ◽  
...  

The present study evaluated: (1) in vivo follicular development in canine ovarian tissue after slow freezing and xenotransplantation; and (2) the use of erythropoietin (EPO) as an angiogenic factor to optimise the transplantation procedure. Frozen–thawed ovarian tissue from five bitches was grafted into severe combined immunodeficient (SCID) mice (n = 47) treated with or without EPO (500 IU kg–1, once daily for 3 days) (Groups A and B, respectively) and analysed after 0, 1, 8 or 16 weeks. Follicle grade, follicle density, follicle morphology and stromal cells density were assessed by histological analysis, whereas vascularisation of the graft was quantified by immunohistochemistry with anti-α-smooth muscle actin antibody. Despite a massive loss of follicles after grafting, secondary follicle density was higher at 8 and 16 weeks than at 1 week regardless of EPO treatment. EPO significantly improved early follicle morphology and stromal cell density after 8 weeks and blood vessel density at 16 weeks after transplantation (P < 0.05). Intact secondary follicles with more than three granulosa cells layers were observed 16 weeks after transplantation. The results suggest that canine ovarian tissue can be successfully preserved by our slow-freezing protocol because the tissue showed follicular growth after xenotransplantation. EPO treatment did not lessen the massive loss of follicles after transplantation.


Ultrasound ◽  
2018 ◽  
Vol 27 (2) ◽  
pp. 85-93
Author(s):  
Justyna Janus ◽  
Baris Kanber ◽  
Wadhah Mahbuba ◽  
Charlotte Beynon ◽  
Kumar V Ramnarine ◽  
...  

Introduction The efficacy of preclinical ultrasound at providing a quantitative assessment of mouse models of vascular disease is relatively unknown. In this study, preclinical ultrasound was used in combination with a semi-automatic image processing method to track arterial distension alterations in mouse models of abdominal aortic aneurysm and atherosclerosis. Methods Longitudinal B-mode ultrasound images of the abdominal aorta were acquired using a preclinical ultrasound scanner. Arterial distension was assessed using a semi-automatic image processing algorithm to track vessel wall motion over the cardiac cycle. A standard, manual analysis method was applied for comparison. Results Mean arterial distension was significantly lower in abdominal aortic aneurysm mice between day 0 and day 7 post-onset of disease (p < 0.01) and between day 0 and day 14 (p < 0.001), while no difference was observed in sham control mice. Manual analysis detected a significant decrease (p < 0.05) between day 0 and day 14 only. Atherosclerotic mice showed alterations in arterial distension relating to genetic modification and diet. Arterial distension was significantly lower (p < 0.05) in Ldlr−/− (++/−−) mice fed high-fat western diet when compared with both wild type (++/++) mice and Ldlr−/− (++/−−) mice fed chow diet. The manual method did not detect a significant difference between these groups. Conclusions Arterial distension can be used as an early marker for the detection of arterial disease in murine models. The semi-automatic analysis method provided increased sensitivity to differences between experimental groups when compared to the manual analysis method.


2010 ◽  
Vol 24 (3) ◽  
pp. 552-560 ◽  
Author(s):  
Nebojsa Andric ◽  
Mika Thomas ◽  
Mario Ascoli

Abstract Ovarian follicular development and differentiation is characterized by dramatic changes in aromatase (Cyp19a1) expression. In preovulatory follicles, activation of the FSH receptor increases aromatase expression until the surge of LH decreases it. Here we provide in vivo evidence that down-regulation of Cyp19a1 by the LH surge requires efficient signaling through the epidermal growth factor receptor (EGFR). The human chorionic gonadotropin (hCG)-induced down-regulation of Cyp19a1 expression in the two different mouse models with inactivating mutations of the EGFR (wa2 and velvet) is impaired but not abolished. The hCG-induced phosphorylation of ovarian ERK1/2, expression of C/EBPβ, and the phosphorylation of Connexin43 (two downstream targets of ERK1/2 action) are also decreased in these two mouse models. In contrast, disruption of EGFR signaling does not have any affect on the hCG-induced phosphorylation of cAMP response element-binding protein or AKT. This study provides the first in vivo evidence linking the LH receptor, the EGFR, and ERK1/2 as sequential components of a pathway that regulates ovarian Cyp19a1 expression.


1928 ◽  
Vol 5 (4) ◽  
pp. 283-291
Author(s):  
ALEXANDER LIPSCHUTZ

The comparative condition of ovarian fragments has been studied in fully grown isolated rabbits, some of which possessed normal ovaries, whilst in others the normal amount of ovarian tissue had been previously reduced by partial castration. No pronounced increase in weight of ovarian tissue was observed in cases of partial castration though the experiments lasted 4½ months; this is contrary to what has been observed in young rabbits. The features characteristic of ovarian fragments in partially castrated hosts were quite definite: (1) the total number of primary follicles was greatly reduced as compared with ovarian fragments present in normal females; (2) the number of large follicles (with a diameter of not less than 1 mm.) in an ovarian fragment grown in a partially castrated animal was not less than that in both ovaries of a normal animal. A diminution in the total number of primary follicles was observed also when calculated per mg. of the original mass of the fragment. The maximum diameter of the follicles in the ovarian fragments in partially castrated rabbits was not greater than in normal ovaries. These observations are in accordance with the "Law of follicular constancy." The deviations from the law of follicular constancy which were formerly observed in partial castration (persistence of mature follicles and formation of follicular cysts) are probably to be explained by a disturbance of the normal balance between formation and use of "X-substances" necessary for follicular development; this disturbance possibly represents a final stage in the life of an ovarian fragment after extensive use has been made of primary follicles. The meaning of ovarian hypertrophy is also discussed. It is suggested that the integrative processes which take place in an ovarian fragment after partial castration are not to be characterised by increase of weight but only by those processes which are dictated by the law of follicular constancy.


2005 ◽  
Vol 49 (7) ◽  
pp. 2634-2641 ◽  
Author(s):  
Jeffry D. Shearer ◽  
Linda Siemann ◽  
Mary Gerkovich ◽  
Robert V. House

ABSTRACT The biological activity of a new intravenous (i.v.) preparation of human vaccinia immune globulin (VIGIV) was evaluated in two mouse models of vaccinia virus (VV) infection. In a mouse tail lesion model, female CD-1 mice were inoculated i.v. with 7 × 104 PFU of VV to produce >10 lesions per tail 8 days later. In a mouse lethality model, female severe combined immunodeficient (SCID) mice were inoculated i.v. with 3 × 104 PFU of VV to produce 100% mortality within 45 days. The ability of VIGIV to reduce tail lesion formation in CD-1 mice and mortality in SCID mice was determined by (i) pretreatment of a lethal VV dose with VIGIV prior to i.v. inoculation into SCID mice and (ii) i.v. administration of VIGIV to CD-1 and SCID mice the day before and up to 8 days after VV infection. VIGIV reduced the proportion of CD-1 mice with >10 tail lesions in a dose-related manner when VIGIV was given 1 day before and up to 1 day after VV inoculation. The pretreatment of VV with VIGIV prolonged survival and decreased mortality. VIGIV (100 and 400 mg/kg) prolonged survival when given up to 4 days after VV inoculation, and the 400-mg/kg dose reduced the mortality rate by 80% when given the day before or immediately after VV inoculation. The biological activity of VIGIV was demonstrated in both the immunocompetent and immunocompromised murine models. The timing of treatment relative to VV inoculation appeared to be important for the demonstration of VIGIV's biological activity.


2003 ◽  
Vol 14 (3) ◽  
pp. 154-174 ◽  
Author(s):  
Tamizchelvi Thyagarajan ◽  
Satish Totey ◽  
Mary Jo S. Danton ◽  
Ashok B. Kulkarni

Targeted gene disruption in mice is a powerful tool for generating murine models for human development and disease. While the human genome program has helped to generate numerous candidate genes, few genes have been characterized for their precise in vivo functions. Gene targeting has had an enormous impact on our ability to delineate the functional roles of these genes. Many gene knockout mouse models faithfully mimic the phenotypes of the human diseases. Because some models display an unexpected or no phenotype, controversy has arisen about the value of gene-targeting strategies. We argue in favor of gene-targeting strategies, provided they are used with caution, particularly in interpreting phenotypes in craniofacial and oral biology, where many genes have pleiotropic roles. The potential pitfalls are outweighed by the unique opportunities for developing and testing different therapeutic strategies before they are introduced into the clinic. In the future, we believe that genetically engineered animal models will be indispensable for gaining important insights into the molecular mechanisms underlying development, as well as disease pathogenesis, diagnosis, prevention, and treatment.


2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Jian Xu ◽  
Si-Yang Li ◽  
Deepak V. Almeida ◽  
Rokeya Tasneen ◽  
Kala Barnes-Boyle ◽  
...  

ABSTRACT Novel regimens combining bedaquiline and pretomanid with either linezolid (BPaL regimen) or moxifloxacin and pyrazinamide (BPaMZ regimen) shorten the treatment duration needed to cure tuberculosis (TB) in BALB/c mice compared to that of the first-line regimen and have yielded promising results in initial clinical trials. However, the independent contribution of the investigational new drug pretomanid to the efficacy of BPaMZ has not been examined, and its contribution to BPaL has been examined only over the first 2 months of treatment. In the present study, the addition of pretomanid to BL increased bactericidal activity, prevented emergence of bedaquiline resistance, and shortened the duration needed to prevent relapse with drug-susceptible isolates by at least 2 months in BALB/c mice. Addition of pretomanid to bedaquiline, moxifloxacin, and pyrazinamide (BMZ) resulted in a 1-log10 greater CFU reduction after 1 month of treatment and/or reduced the number of mice relapsing in each of 2 experiments in BALB/c mice and in immunocompromised nude mice. Bedaquiline-resistant isolates were found at relapse in only one BMZ-treated nude mouse. Treatment of infection with a pyrazinamide-resistant mutant in BALB/c mice with BPaMZ prevented selection of bedaquiline-resistant mutants and reduced the proportion of mice relapsing compared to that for BMZ treatment alone. Among severely ill C3HeB/FeJ mice with caseous pneumonia and cavitation, BPaMZ increased median survival (≥60 versus 21 days) and reduced median lung CFU by 2.4 log10 at 1 month compared to the level for BMZ. In conclusion, in 3 different mouse models, pretomanid contributed significantly to the efficacy of the BPaMZ and BPaL regimens, including restricting the selection of bedaquiline-resistant mutants.


Reproduction ◽  
2011 ◽  
Vol 141 (4) ◽  
pp. 481-490 ◽  
Author(s):  
V von Schönfeldt ◽  
R Chandolia ◽  
L Kiesel ◽  
E Nieschlag ◽  
S Schlatt ◽  
...  

Improvements in cancer survival rates have renewed interest in the cryopreservation of ovarian tissue for fertility preservation. We used the marmoset as a non-human primate model to assess the effect of different cryoprotectives on follicular viability of prepubertal compared to adult ovarian tissue following xenografting. Cryopreservation was performed with dimethylsulfoxide (DMSO), 1,2-propanediol (PrOH), or ethylene glycol (EG) using a slow freezing protocol. Subsequently, nude mice received eight grafts per animal from the DMSO and the PrOH groups for a 4-week grafting period. Fresh, cryopreserved–thawed, and xenografted tissues were serially sectioned and evaluated for the number and morphology of follicles. In adult tissue, the percentage of morphologically normal primordial follicles significantly decreased from 41.2±4.5% (fresh) to 13.6±1.8 (DMSO), 9.5±1.7 (PrOH), or 6.8±1.0 (EG) following cryopreservation. After xenografting, the percentage of morphologically normal primordial (26.2±2.5%) and primary follicles (28.1±5.4%) in the DMSO group was significantly higher than that in the PrOH group (12.2±3 and 5.4±2.1% respectively). Proliferating cell nuclear antigen (PCNA) staining suggests the resumption of proliferative activity in all cellular compartments. In prepubertal tissues, primordial but not primary follicles display a similar sensitivity to cryopreservation, and no significant differences between DMSO and PrOH following xenografting were observed. In conclusion, DMSO shows a superior protective effect on follicular morphology compared with PrOH and EG in cryopreserved tissues. Xenografting has confirmed better efficacy of DMSO versus PrOH in adult but not in prepubertal tissues, probably owing to a greater capacity of younger animals to compensate for cryoinjury.


2002 ◽  
Vol 11 (3) ◽  
pp. 115-132 ◽  
Author(s):  
Ernesto Bockamp ◽  
Marko Maringer ◽  
Christian Spangenberg ◽  
Stephan Fees ◽  
Stuart Fraser ◽  
...  

The ability to engineer the mouse genome has profoundly transformed biomedical research. During the last decade, conventional transgenic and gene knockout technologies have become invaluable experimental tools for modeling genetic disorders, assigning functions to genes, evaluating drugs and toxins, and by and large helping to answer fundamental questions in basic and applied research. In addition, the growing demand for more sophisticated murine models has also become increasingly evident. Good state-of-principle knowledge about the enormous potential of second-generation conditional mouse technology will be beneficial for any researcher interested in using these experimental tools. In this review we will focus on practice, pivotal principles, and progress in the rapidly expanding area of conditional mouse technology. The review will also present an internet compilation of available tetracycline-inducible mouse models as tools for biomedical research ( http://www.zmg.uni-mainz.de/tetmouse/ ).


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