Animal Studies in Endometriosis: A Review

Story, Lisa; Kennedy, Stephen

doi:10.1093/ilar.45.2.132

Cited by 84 publications

(84 citation statements)

References 36 publications

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“…Part of this may be due to a lack of sufficient and adequate animal models. 76 Angiogenesis has been shown to play a role in endometriosis both in human disease and in animal models. We show that growth of endometriotic lesions and early angiogenesis can be monitored noninvasively using a model of luciferase transgenic mice.…”

Section: Discussionmentioning

confidence: 99%

A Novel Noninvasive Model of Endometriosis for Monitoring the Efficacy of Antiangiogenic Therapy

Becker

Wright

Satchi‐Fainaro

et al. 2006

The American Journal of Pathology

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Endometriosis, the presence of ectopic endometrial tissue, is a common disease associated with high morbidity and socioeconomic problems. Angiogenesis, the formation of new blood vessels, plays an important role in the formation and growth of endometriotic lesions. We have created a novel, noninvasive model to monitor the growth of these lesions and the associated angiogenesis in vivo. First, we generated luciferase-expressing transgenic mice by inserting the human ubiquitin C promoter coupled to the firefly luciferase reporter. Injection of luciferin in these mice causes full-body bioluminescence, which can be detected using a lowlight CCD camera. Endometrial tissue from these transgenic mice was surgically implanted into nonluminescent recipients. Bioluminescence of lesions was noninvasively imaged after intravenous or intraperitoneal injection of luciferin. Transabdominal luminescence compared well with the location of the transgenic endometriotic lesions, and lesion size correlated with the intensity of luminescence. Systemic treatment with the angiogenesis inhibitors caplostatin and endostatin peptide mP-1 delayed and suppressed the onset and intensity of the luminescent signal. Caplostatin suppressed the growth of endometriotic lesions by 59% compared with controls. This novel, noninvasive model of endometriosis provides a means to study early angiogenesis in vivo and to monitor endometriotic growth and the efficacy of systemic antiangiogenic therapy.

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Section: Discussionmentioning

confidence: 99%

A Novel Noninvasive Model of Endometriosis for Monitoring the Efficacy of Antiangiogenic Therapy

Becker

Wright

Satchi‐Fainaro

et al. 2006

The American Journal of Pathology

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“…Despite the clear advantages of using animal models in biomedical research, whether results obtained using experimental models of disease could be extrapolated to the human scenario remains controversial (4)(5)(6)(7). Therefore, animal models need to be carefully evaluated to ensure that they accurately represent the disease they are meant to mimic.…”

Section: Introductionmentioning

confidence: 99%

Molecular profiling of experimental endometriosis identified gene expression patterns in common with human disease

Flores

Rivera

Ruiz

et al. 2007

Fertility and Sterility

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OBJECTIVE-To validate a rat model of endometriosis using cDNA microarrays by identifying common gene expression patterns beween experimental and natural disease. DESIGN-Autotransplantation rat model. SETTING-Medical school department. ANIMALS-Female Sprague-Dawley rats.INTERVENTIONS-Endometriosis was surgically-induced by suturing uterine horn implants next to the small intestine's mesentery. Control rats received sutures with no implants. After 60 days, endometriotic implants and uterine horn were obtained. MAIN OUTCOME MEASURES-Gene expression levels determined by cDNA microarrays and QRT-PCR.METHODS-Cy5-labeled cDNA was synthesized from total RNA obtained from endometriotic implants. Cy3-labeled cDNA was synthesized using uterine RNA from a control rat. Gene expression levels were analyzed after hybridizing experimental and control labeled cDNA to PIQOR ™ Toxicology Rat Microarrays (Miltenyi Biotec) containing 1,252 known genes. Cy5/Cy3 ratios were determined and genes with >2-fold higher or <0.5-fold lower expression levels were selected. Microarray results were validated by QRT-PCR.RESULTS-We observed differential expression of genes previously shown to be upregulated in patients, including growth factors, inflammatory cytokines/receptors, tumor invasion/metastasis factors, adhesion molecules, and anti-apoptotic factors.CONCLUSIONS-This study presents evidence in support of using this rat model to study the natural history of endometriosis and test novel therapeutics for this incurable disease.

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“…Controlled experiments in humans are difficult due to limitations on repeated imaging and surgical biopsies for disease monitoring (Story and Kennedy, 2004). Therefore, animal models provide an invaluable tool for studying complex diseases like endometriosis.…”

Section: Rhesus Macaque As a Model For Endometriosismentioning

confidence: 99%

Spontaneous endometriosis in rhesus macaques: evidence for a genetic association with specific Mamu-A1 alleles

Kondova¹,

Braskamp²,

Heidt³

et al. 2017

Primate Biol.

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Abstract. Endometriosis is a poorly understood common debilitating women's reproductive disorder resulting from proliferative and ectopic endometrial tissue associated with variable clinical symptoms including dysmenorrhea (painful menstrual periods), dyspareunia (pain on intercourse), female infertility, and an increased risk of malignant transformation. The rhesus macaque (Macaca mulatta) develops a spontaneous endometriosis that is very similar to that seen in women. We hypothesized that specific major histocompatibility complex (MHC) alleles may contribute to the pathogenesis of endometriosis. As part of a collaboration between the Biomedical Primate Research Centre (BPRC) in the Netherlands and the New England Primate Research Center (NEPRC) in the United States, we analyzed DNA sequences of MHC class I (Macaca mulatta, Mamu-A1) and class II (Mamu-DRB) alleles from rhesus macaques with endometriosis and compared the allele frequencies with those of age-matched healthy macaques. We demonstrate that two MHC class I alleles are overrepresented in diseased macaques compared to controls: Mamu-A1*001, 33.3 % in BPRC animals with endometriosis vs. 11.6 % in healthy macaques (p = 0.007), and Mamu-A1*007, 21.9 % NEPRC rhesus macaques vs. 6.7 %, (p = 0.003). We provide evidence that select MHC class I alleles are associated with endometriosis in rhesus macaques and suggest that the disease pathogenesis contribution of MHC class I warrants further research.

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Animal Studies in Endometriosis: A Review

Cited by 84 publications

References 36 publications

A Novel Noninvasive Model of Endometriosis for Monitoring the Efficacy of Antiangiogenic Therapy

A Novel Noninvasive Model of Endometriosis for Monitoring the Efficacy of Antiangiogenic Therapy

Molecular profiling of experimental endometriosis identified gene expression patterns in common with human disease

Spontaneous endometriosis in rhesus macaques: evidence for a genetic association with specific Mamu-A1 alleles

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