Chronic endometritis: A prevalent yet poorly understood entity

Margulies, Samantha L.; Flores, Valerie A.; Parkash, Vinita; Pal, Lubna

doi:10.1002/ijgo.13962

Cited by 10 publications

(5 citation statements)

References 21 publications

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“…At last, Considering the absence of a clear understanding of chronic endometritis diagnosis, we still need to further explore the diagnostic criteria of endometritis to facilitate the management and treatment of patients. 36 , 37 …”

Section: Discussionmentioning

confidence: 99%

LPS-Induced Activation of the cGAS-STING Pathway is Regulated by Mitochondrial Dysfunction and Mitochondrial DNA Leakage in Endometritis

Li¹,

Wen²,

Liu³

et al. 2022

JIR

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Introduction: Chronic endometritis is a common disease in women of childbearing age and can cause pelvic inflammatory disease. The cGAS-STING pathway plays an important role in many inflammatory diseases. Purpose: The aim of this study was to investigate the relationship between the cGAS-STING pathway and endometritis. Methods: We collected endometrium samples from patients with endometritis to detect changes in the cGAS-STING pathway. In vitro, human endometrial stromal cells (HESC) were stimulated with lipopolysaccharide (LPS), and a mouse STING gene-knockout model was established by CRISPR/cas9 for STING to further explore the mechanism underlying its effects in endometritis. We used Western blotting (WB) and immunohistochemical staining to detect the variations in protein levels and real-time PCR to study the variations in gene expression. Results: We observed the activation of the cGAS-STING pathway and an increase in the expression of cytokine-encoding genes, including IL-8, IL-6, IL-1β, and IFN-β1, in endometrial tissues of patients with endometritis. Stimulation of HESCs using LPS demonstrated increase in the expression of proteins involved the cGAS-STING pathway and the gene expression of inflammatory cytokines. STING-knockdown experiments demonstrated a decrease in the gene expression levels of inflammatory cytokines. Moreover, we also identified the translocation of IRF3 and STING after LPS stimulation. Regarding mitochondrial function, LPS led to an increase in reactive oxygen species levels and a reduction in mitochondrial membrane potential. However, we observed that the mitochondrial DNA (mtDNA) leaked into the cytoplasm, upregulating the levels of proteins involved in the cGAS-STING pathway upon LPS stimulation. Furthermore, our results showed that LPS induced hyperemia, inflammatory factor production, and expression of Pho-TBK1 in wild-type mice compared with the levels in control mice, and STING gene-knockdown alleviated these effects. Conclusion: LPS induces mitochondrial dysfunction in endometrial stromal cells, resulting in mtDNA leakage and promoting endometritis by stimulating the cGAS-STING pathway.

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Section: Discussionmentioning

confidence: 99%

LPS-Induced Activation of the cGAS-STING Pathway is Regulated by Mitochondrial Dysfunction and Mitochondrial DNA Leakage in Endometritis

Li¹,

Wen²,

Liu³

et al. 2022

JIR

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“…In recent years, the Human Microbiome Project (HMP) has found that about 9% of human microbiota exists in female genital tract ( Margulies et al., 2022 ). In the past, it was believed that female genital tract microorganisms only inhabit the vagina, vulva, anus and so on.…”

Section: Introductionmentioning

confidence: 99%

“…These low abundance microbiota constitute the intrauterine microecology. Many studies, including HMP, have found the importance of microorganisms and their genomes in human health and disease ( Chen et al., 2017 ; Margulies et al., 2022 ). So we boldly speculate that chronic endometritis (CE), endometrial polyps (EP), and even endometrial cancer may occur when the microbiota in the uterus changes or pathogens invade.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the microbiota composition in the genital tract of infertile patients with chronic endometritis or endometrial polyps

Liang

Ling

Zhang

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundThe previous researches show that infertile patients have a higher incidence of endometritis and endometrial polyps, and the occurrence of these two diseases is related to changes in the microbiota of the genital tract. We aim to determine the composition and changing characteristics of the microbiota in the genital tract (especially the endometrium) of infertile patients with chronic endometritis or endometrial polyps, and find the correlation between it and the occurrence of diseases.MethodsThis is a prospective study. We collected genital tract biopsy samples from 134 asymptomatic infertile patients receiving assisted reproductive therapy before embryo transfer. Through pathological examination and 16S ribosomal RNA(16S rRNA) sequencing, we determined the distribution of chronic endometritis and endometrial polyps in these patients, as well as their distribution of reproductive tract microorganisms.ResultsCompared with the normal control group, the microbial group of reproductive tract in patients with chronic endometritis and endometrial polyps is changed, and there are significant species differences and relative abundance differences in the vagina, cervix and uterine cavity. Lactobacillus, the dominant flora of female genital tract, showed a change in abundance in patients with endometrial diseases. Endometrial microbiota composed of Staphylococcus, Gardnerella, Atopobium, Streptococcus, Peptostreptococcus, Chlamydia, Fusobacterium, Acinetobacter, etc. are related to chronic endometritis and endometrial polyps.ConclusionThe results showed that, compared with the normal control group, the endometrial microbiota of infertile patients with chronic endometritis or endometrial polyps did have significant changes in the relative abundance distribution of species, suggesting that changes in local microecology may be an important factor in the occurrence of disease, or even adverse pregnancy outcomes. The further study of endometrial microecology may provide a new opportunity to further improve the diagnosis and treatment strategy of chronic endometritis.

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“…There is still no consensus regarding the clinical significance of CE, with no definitive evidence to support the hypothesis that CE is always associated with adverse reproductive outcomes ( 9 , 10 ). The higher prevalence of CE in patients with recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), and preterm delivery, however, does support the belief that CE may adversely affect some reproductive outcomes in IVF ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Chronic endometritis diagnosed using a cut-off of ≥5 CD138 plasma cells significantly affects the reproductive outcomes of frozen embryo transfer: a case-control study

Bulut,

Yeğinaltay,

Tunç

et al. 2023

J Turkish German Gynecol Assoc

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Objective: To investigate the clinical significance of a diagnosis of chronic endometritis (CE) made using a diagnostic cut-off of ≥1 or ≥5 CD138 plasma cells per high power field (HPF) in asymptomatic patients undergoing in vitro fertilization (IVF) with frozen embryo transfer (FET). Material and Methods: In this retrospective case-control study, 1,865 patients underwent freeze-all-IVF treatment between January and December 2019, with 419 undergoing endometrial biopsies at oocyte retrieval. Of the 419 biopsy-patients, 301 have since undergone first FET. The processed endometrial biopsies of the 301 patients underwent immunohistochemical (IHC) examination with anti-CD138 to count CD138+ plasma cells per HPF. CE diagnosis was defined as 0 CD138 plasma cells (control-group), ≥1 CD138 plasma cells (CE control -group) or ≥5 CD138 plasma cells (CE disease -group) per HPF. Results: Twenty-six (8.6%) patients were retrospectively diagnosed having ≥1 CD138 plasma cells, and five patients (1.7%) having ≥5 CD138 plasma cells (CE disease -group) per HPF. The live birth and pregnancy loss rates of the three groups were 52.7% and 27.9%, 53.8% and 26.3% and 20.0% and 66.7%, respectively. The antral follicle count (AFC) of the three groups were 15.0 (9.0-22.0), 10.5 (7.75-15.25), and 6.0 (5.0-14.0), respectively. Conclusion: Asymptomatic patients diagnosed with CE with ≥5 CD138 plasma cells per HPF, had the lowest live birth and highest pregnancy loss rates, with these patients also having significantly reduced AFC.

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Chronic endometritis: A prevalent yet poorly understood entity

Cited by 10 publications

References 21 publications

LPS-Induced Activation of the cGAS-STING Pathway is Regulated by Mitochondrial Dysfunction and Mitochondrial DNA Leakage in Endometritis

LPS-Induced Activation of the cGAS-STING Pathway is Regulated by Mitochondrial Dysfunction and Mitochondrial DNA Leakage in Endometritis

Analysis of the microbiota composition in the genital tract of infertile patients with chronic endometritis or endometrial polyps

Chronic endometritis diagnosed using a cut-off of ≥5 CD138 plasma cells significantly affects the reproductive outcomes of frozen embryo transfer: a case-control study

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