The copper chelator ammonium tetrathiomolybdate inhibits the progression of experimental endometriosis in TNFR1-deficient mice Original paper
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Women’s Health
Women’s Health
Women’s health, a vital aspect of medical science, encompasses various conditions unique to women’s physiological makeup. Historically, women were often excluded from clinical research, leading to a gap in understanding the intricacies of women’s health needs. However, recent advancements have highlighted the significant role that the microbiome plays in these conditions, offering new insights and potential therapies. MicrobiomeSignatures.com is at the forefront of exploring the microbiome signature of each of these conditions to unravel the etiology of these diseases and develop targeted microbiome therapies.
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Metals
Metals
OverviewHeavy metals play a significant and multifaceted role in the pathogenicity of microbial species. Their involvement can be viewed from two primary perspectives: the toxicity of heavy metals to microbes and the exploitation of heavy metals by microbial pathogens to establish infections and evade the host immune response. Understanding these aspects is critical for both […]
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What Was Studied?
This study evaluated the therapeutic potential of ammonium tetrathiomolybdate (TM), a copper chelator, in inhibiting the progression of experimental endometriosis (EDT) in TNFR1-deficient mice. It explored TM’s effects on copper and estradiol concentrations, lesion development, angiogenesis, oxidative stress, and inflammatory pathways. The research aimed to address how TM mitigates EDT in a worsened state caused by TNFR1 deficiency, a condition characterized by reduced cell death and increased lesion proliferation.
Who Was Studied?
The subjects were TNFR1-deficient female C57BL/6 mice divided into three groups: sham-operated (KO Sham), EDT-induced (KO EDT), and EDT-induced with TM treatment (KO EDT+TM). EDT was induced via autologous uterine tissue transplantation into the intestinal mesentery, and TM was administered orally postoperatively. Experimental outcomes were evaluated one month after EDT induction.
Most Important Findings
The study revealed several critical findings. First, EDT induction significantly elevated copper and estradiol levels in the peritoneal fluid, both of which were restored to physiological levels with TM treatment. TM also reduced lesion volume and weight, decreased cell proliferation, and suppressed angiogenesis, as evidenced by lower blood vessel counts and reduced expression of Vegfa, Fgf2, and Pdgfb. Furthermore, TM altered oxidative stress markers, decreasing the activity of superoxide dismutase (SOD) and catalase (CAT) while increasing lipid peroxidation, suggesting a pro-oxidative environment conducive to apoptotic signaling.
From a microbiome perspective, copper’s role as a metalloestrogen and its involvement in estradiol synthesis underline the relevance of copper chelation in addressing estrogen-dependent diseases like endometriosis. By reducing copper levels, TM may disrupt microbial contributions to oxidative stress and inflammation, though direct microbiome-specific findings were not explored.
Greatest Implications
The study’s findings suggest TM’s dual role in reducing pro-inflammatory and pro-angiogenic pathways while restoring copper and estradiol homeostasis. These mechanisms are vital for mitigating EDT progression, particularly in the context of TNFR1 deficiency, where pathological signaling is exacerbated. Clinically, TM represents a potential adjunct therapy for managing endometriosis, particularly in cases resistant to conventional hormone treatments. The findings also reinforce the broader therapeutic relevance of targeting trace metals like copper in inflammatory and estrogen-dependent conditions.
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.
Metalloestrogens
Metalloestrogens are metals that activate the estrogen receptor in the absence of estradiol.