Endometriosis leads to central nervous system-wide glial activation in a mouse model of endometriosis

Shah Tauseef Bashir, S.T. Bashir, Catherine Redden, Catherine R Redden, Kishori Raj, Rachel B Arcanjo, Sandra Stasiak, Quanxi Li, Andrew J Steelman, Romana A Nowak
Journal of neuroinflammation · 2023 · vol. 20(1) , pp. 59 · doi:10.1186/s12974-023-02713-0 · PMID:36879305 · PMC9987089 · W4323315034
article OA: gold CC0 ⤵ 21 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study found that endometriosis in mice causes increased microglial soma size and GFAP-positive area in multiple brain regions, along with elevated TNF and IL6 expression.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 ⓘ

This study used a syngeneic mouse model of endometriosis induced by intra-peritoneal transfer of uterine tissue fragments, with sham-surgery controls, and examined brain and spinal cord tissues across 4, 8, 16, and 32 days after induction. Using immunohistochemistry, the authors assessed microglial morphology with IBA1 and astrocyte area with GFAP in multiple brain regions, alongside inflammatory markers TNF and IL6, and they performed behavioral pain assays including burrowing and von Frey testing. Mice with endometriosis showed increased microglial soma size in several brain regions (cortex, hippocampus, thalamus, hypothalamus) at later timepoints, increased IBA1- and GFAP-positive area by day 16, and higher combined TNF/IL6 expression, while microglia and astrocyte counts were unchanged. The paper explicitly frames these results as the first report of central nervous system-wide glial activation, but the approach remains limited by its reliance on selected markers/regions and aggregated cytokine readouts, rather than more direct measures of glial function. This paper is centrally about endometriosis — it demonstrates CNS-wide glial activation (microglia and astrocytes) in a mouse model and links it to endometriosis-associated chronic pelvic pain–related behaviors.

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Abstract

BACKGROUND: Chronic pelvic pain (CPP) is a common symptom of endometriosis. Women with endometriosis are also at a high risk of suffering from anxiety, depression, and other psychological disorders. Recent studies indicate that endometriosis can affect the central nervous system (CNS). Changes in the functional activity of neurons, functional magnetic resonance imaging signals, and gene expression have been reported in the brains of rat and mouse models of endometriosis. The majority of the studies thus far have focused on neuronal changes, whereas changes in the glial cells in different brain regions have not been studied. METHODS: Endometriosis was induced in female mice (45-day-old; n = 6-11/timepoint) by syngeneic transfer of donor uterine tissue into the peritoneal cavity of recipient animals. Brains, spines, and endometriotic lesions were collected for analysis at 4, 8, 16, and 32 days post-induction. Sham surgery mice were used as controls (n = 6/timepoint). The pain was assessed using behavioral tests. Using immunohistochemistry for microglia marker ionized calcium-binding adapter molecule-1 (IBA1) and machine learning "Weka trainable segmentation" plugin in Fiji, we evaluated the morphological changes in microglia in different brain regions. Changes in glial fibrillary acidic protein (GFAP) for astrocytes, tumor necrosis factor (TNF), and interleukin-6 (IL6) were also evaluated. RESULTS: We observed an increase in microglial soma size in the cortex, hippocampus, thalamus, and hypothalamus of mice with endometriosis compared to sham controls on days 8, 16, and 32. The percentage of IBA1 and GFAP-positive area was increased in the cortex, hippocampus, thalamus, and hypothalamus in mice with endometriosis compared to sham controls on day 16. The number of microglia and astrocytes did not differ between endometriosis and sham control groups. We observed increased TNF and IL6 expression when expression levels from all brain regions were combined. Mice with endometriosis displayed reduced burrowing behavior and hyperalgesia in the abdomen and hind-paw. CONCLUSION: We believe this is the first report of central nervous system-wide glial activation in a mouse model of endometriosis. These results have significant implications for understanding chronic pain associated with endometriosis and other issues such as anxiety and depression in women with endometriosis.

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Condition tags

endometriosischronic_pelvic_pain

MeSH descriptors

Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Chronic Pain Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Animals Animals Animals Animals Animals

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