Sex Differences in Experimentally Induced Colitis in Mice: a Role for Estrogens

Bábíčková, Janka; Tóthová, Ľubomíra; Lengyelová, E.; Bartoňová, Anastázie; Hodosy, Július; Gardlík, Roman; Celec, Peter

doi:10.1007/s10753-015-0180-7

Cited by 110 publications

(69 citation statements)

References 43 publications

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“…It indicates the presence of a higher number of granulocytes in the intestine of colitic males compared to females. Nevertheless, this is consistent with previous studies, while it can be theorized that testosterone might also influence the activity of neutrophils, which are the main MPO producers [43–45]. …”

Section: Discussionsupporting

confidence: 93%

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Sex Differences in the Effect of Resveratrol on DSS-Induced Colitis in Mice

Wagnerová

Bábíčková

Lipták

et al. 2017

Gastroenterology Research and Practice

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Resveratrol is a natural polyphenol studied for its possible protective properties in inflammatory bowel diseases. Moreover, it has been shown to interact with estrogen receptors. In the present study, we aimed to investigate possible diverse effects of resveratrol on female and male mice in DSS-induced colitis. Thirty-seven C57BL/6 mice (21 female and 16 male) were divided into three groups for each sex. The first group received pure water (CTRL). The other two groups received 1.5% dextran sulfate sodium (DSS) to induce colitis from which one group was treated with resveratrol (DSS + RSV). Intake of 1.5% DSS caused weight loss in all DSS groups compared to control mice. Weight loss, stool consistency, and discomfort did not show any protective effect of resveratrol in males and showed even adverse effects in females. In females, the activity of myeloperoxidase was lower compared to that in males. However, colon length and spleen weight showed no sex differences, which can indicate the induction of only mild colitis in mice. Resveratrol did not have any effect on TNF-alpha levels. Taken together, these results for the first time propose possible diverse effects of resveratrol in DSS-induced colitis model depending on the sex of the animal. However, this conclusion must be confirmed by further analyses.

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Section: Discussionsupporting

confidence: 93%

“…In our previous study, we showed that during DSS-induced colitis, female mice have milder course of disease presumably mediated by estradiol [43]. We attribute the opposite results of the current study to the ability of resveratrol to interact with estrogen receptors and especially its feature as possible estrogen inhibitor [25, 29].…”

Section: Discussioncontrasting

confidence: 57%

Sex Differences in the Effect of Resveratrol on DSS-Induced Colitis in Mice

Wagnerová

Bábíčková

Lipták

et al. 2017

Gastroenterology Research and Practice

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“…For example, estradiol supplementation of ovariectomized mice ameliorated the severity of colitis [21]. Villa et al [22] showed that the activation of the intracellular estrogen receptor by estradiol shortened the LPS-induced pro-inflammatory phase and, by influencing the intrinsic and extrinsic programs, triggered the resolution of inflammation in RAW 264.7 cells through the regulation of the SOCS3 and STAT3 signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

G Protein-Coupled Receptor 30 (GPR30) Expression Pattern in Inflammatory Bowel Disease Patients Suggests its Key Role in the Inflammatory Process. A Preliminary Study

Włodarczyk

Sobolewska-Włodarczyk

Cygankiewicz

et al. 2020

JGLD

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Background & Aims: G protein-coupled receptor 30 (GPR30) is a recently de-orphanized estrogen receptor that mediates the effects of estrogens on different cells. It has been postulated that in inflammatory bowel diseases (IBD) activation of GPR30 blocks the pathways dependent on pro-inflammatory cytokines. The aim of our study was to investigate GPR30 expression in patients with IBD and its potential implication in future therapies.Methods. Fifty-seven patients were enrolled in our study: 20 subjects with Crohn’s disease (CD), 22 with ulcerative colitis (UC) and 15 controls. In each subject, biopsies were taken from various left-colonic locations. Gene and protein expression of GPR30 was quantified using real time RT-PCR or Western blot.Results: GPR30 mRNA and protein expression were detected in all tested colonic tissues. No significant differences in GPR30 gene expression were observed. In non-inflamed areas, GPR30 protein was strongly increased in CD patients, but moderately in UC patients (p= 0.014 and p=0.143, respectively, vs. controls). In CD patients, a significantly lower GPR30 protein content in inflamed than in non-inflamed tissue was observed (p=0.039). The change was independent of patient gender.Conclusion: Our observations indicate that GPR30 may play a role in the development and progression of inflammatory lesions in IBD, thus affecting disease severity, and consequently IBD treatment. Therefore, GPR30 may become an attractive target for novel anti-IBD drugs, particularly in CD.Abbreviations: CRP: C-reactive protein; C-IBS: constipation-predominant IBS; CD: Crohn’s disease; D-IBS: diarrhea-predominant IBS; ER: Estrogen; GPER: G protein – coupled estrogen receptor 1; GPR30: G protein-coupled receptor 30; GI: gastrointestinal; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; IBD: inflammatory bowel diseases; IL: Interleukin; ICAM-1: intracellular cell adhesion molecule-1; IBS: irritable bowel syndrome; PDL: periodontal ligament; Th: T helper; TNF-α: tumor necrosis factor-α; UC: ulcerative colitis; VCAM-1: vascular cell adhesion molecule-1; WBC: white blood cells.

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“…Oestrogen therefore acts at multiple levels of the GIT and plays an important role in maintaining health or causing disease. Estrogens are implicated in driving experimental colitis in mouse models [55], although certain murine colitis models are not affected by estrogens [56]. …”

Section: Sex Hormones Drive Microbiota Differences In Rodent Modelsmentioning

confidence: 99%

The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility

et al. 2018

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Sex differences in immunity are well described in the literature and thought to be mainly driven by sex hormones and sex-linked immune response genes. The gastrointestinal tract (GIT) is one of the largest immune organs in the body and contains multiple immune cells in the GIT-associated lymphoid tissue, Peyer’s patches and elsewhere, which together have profound effects on local and systemic inflammation. The GIT is colonised with microbial communities composed of bacteria, fungi and viruses, collectively known as the GIT microbiota. The GIT microbiota drives multiple interactions locally with immune cells that regulate the homeostatic environment and systemically in diverse tissues. It is becoming evident that the microbiota differs between the sexes, both in animal models and in humans, and these sex differences often lead to sex-dependent changes in local GIT inflammation, systemic immunity and susceptibility to a range of inflammatory diseases. The sexually dimorphic microbiome has been termed the ‘microgenderome’. Herein, we review the evidence for the microgenderome and contemplate the role it plays in driving sex differences in immunity and disease susceptibility. We further consider the impact that biological sex might play in the response to treatments aimed at manipulating the GIT microbiota, such as prebiotics, live biotherapeutics, (probiotics, synbiotics and bacteriotherapies) and faecal microbial transplant. These alternative therapies hold potential in the treatment of both psychological (e.g., anxiety, depression) and physiological (e.g., irritable bowel disease) disorders differentially affecting males and females.

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Sex Differences in Experimentally Induced Colitis in Mice: a Role for Estrogens

Cited by 110 publications

References 43 publications

Sex Differences in the Effect of Resveratrol on DSS-Induced Colitis in Mice

Sex Differences in the Effect of Resveratrol on DSS-Induced Colitis in Mice

G Protein-Coupled Receptor 30 (GPR30) Expression Pattern in Inflammatory Bowel Disease Patients Suggests its Key Role in the Inflammatory Process. A Preliminary Study

The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility

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