Deep Invasive Endometriosis Lesions of the Rectosigmoid May Be Related to Alterations in Cell Kinetics

Bassi, Marco; Arias, Victor; Filho, Nicolau D’Amico; Gueuvoghlanian-Silva, Bárbara Yasmin; Abrão, Maurício Simões; Podgaec, Sérgio

doi:10.1177/1933719115574341

Cited by 9 publications

(6 citation statements)

References 36 publications

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“…Endometriosis is a systemic and reversible inflammatory condition, and treatment of endometriosis has been shown to be beneficial for future fertility and improved pregnancy outcomes[ 17 , 50 ]. Previous studies have shown that the expression of TOP2A was significantly lower in the endometriosis group than in the control group [ 34 ], indicating that the expression pattern of TOP2A in endometriosis is the same as that in RIF in our study. Therefore, we hypothesized that the expression changes of TOP2A may be helpful for evaluating the status and function of the endometrium.…”

Section: Discussionsupporting

confidence: 76%

“…However, it is highly expressed in ovarian cancer and breast cancer, and its expression is closely related to tumor progression, recurrence and poor prognosis [ 32 , 33 ]. Bassi MA et al found that the expression of TOP2A in the endometrium is decreased in patients with endometriosis [ 34 ]. Therefore, we speculate that TOP2A may lead to implantation failure by affecting the proliferation and differentiation of endometrial stromal cells in patients with RIF.…”

Section: Discussionmentioning

confidence: 99%

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TOP2A deficit-induced abnormal decidualization leads to recurrent implantation failure via the NF-κB signaling pathway

Wang

Chen

et al. 2022

Reprod Biol Endocrinol

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Background Successful implantation is a complex process that is influenced by embryo quality, endometrial receptivity, immune factors, and the specific type of in vitro fertilization protocol used. DNA topoisomerase IIα (TOP2A) is a well-known protein involved in cell proliferation; however, its expression and effect on the endometrium in recurrent implantation failure (RIF) have not been fully elucidated. Methods The human endometrial tissues of healthy controls and patients with RIF were collected. A proteomic analysis was performed to evaluate the differentially expressed proteins between the RIF group and the fertile control group. The expression patterns of TOP2A in the human preimplantation endometrium of the patients with RIF were determined by immunohistochemical staining, Western blotting and qRT-PCR. TOP2A knockdown (sh-TOP2A) T-HESCs were generated using lentiviruses. The expression of TOP2A in T-HESCs was manipulated to investigate its role in decidualization. The TOP2A-related changes in decidualization were screened by mRNA sequencing in decidualized TOP2A knockdown and control T-HESCs and then confirmed by Western blotting and immunofluorescence staining. TOP2A-deficient mice were generated by injection of TOP2A-interfering adenovirus on GD2.5 and GD3.5. Results We performed a proteomic analysis of endometrial tissues to investigate the potential pathogenesis of RIF by comparing the patients with RIF and the matched controls and found that TOP2A might be a key protein in RIF. TOP2A is ubiquitously expressed in both stromal and glandular epithelial cells of the endometrium. The data indicate that TOP2A expression is significantly lower in the mid-secretory endometrium of women with RIF. TOP2A expression was downregulated under stimulation by 8-bromo-cAMP and MPA. Ablation of TOP2A resulted in upregulated expression of decidual biomarkers and morphological changes in the cells. Mechanistic analysis revealed that TOP2A regulates the NF-κB signaling pathway in decidualized T-HESCs. The TOP2A-deficient mice exhibited lower fetal weights. Conclusions Our findings revealed that abnormal expression of TOP2A affects decidualization and changes the “window of implantation”, leading to RIF. TOP2A participates in the processes of decidualization and embryo implantation, functioning at least in part through the NF-κB pathway. Regulating the expression of TOP2A in the endometrium may become a new strategy for the prevention and treatment of RIF.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

TOP2A deficit-induced abnormal decidualization leads to recurrent implantation failure via the NF-κB signaling pathway

Wang

Chen

et al. 2022

Reprod Biol Endocrinol

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“…Another study found the TP53 expression to be the highest in OMA, followed by colorectal endometriosis (presumably DE) and then SPE—all in the epithelial , but not stromal, component . One study found no difference in TP53 expression between ectopic and control endometrium, the others found no TP53 expression in endometriosis, OMA, and DE . One recent study reported downregulation of TP53 in OMA, which is concomitant with increased expression of genes involved in autophagy and elevated protein expression of heme oxygenase‐1 (HO‐1), a sign of oxidative stress …”

Section: Mutations Of Cancer Driver Genes In Endometriosis and Their mentioning

confidence: 99%

“…95 One study found no difference in TP53 expression between ectopic and control endometrium, 96 the others found no TP53 expression in endometriosis, 97 OMA, 98,99 and DE. 100 One recent study reported downregulation of TP53 in OMA, which is concomitant with increased expression of genes involved in autophagy and elevated protein expression of heme oxygenase-1 (HO-1), a sign of oxidative stress. 101 Based on the findings published so far and reviewed above, there are reasons to believe that TP53 is likely to be downregulated or even silenced in endometriotic lesions.…”

Section: Tp53mentioning

confidence: 99%

Cancer driver mutations in endometriosis: Variations on the major theme of fibrogenesis

Guo

2018

Reprod Medicine & Biology

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BackgroundOne recent study reports cancer driver mutations in deep endometriosis, but its biological/clinical significance remains unclear. Since the natural history of endometriosis is essentially gradual progression toward fibrosis, it is thus hypothesized that the six driver genes reported to be mutated in endometriosis (the RP set) may play important roles in fibrogenesis but not necessarily malignant transformation.MethodsExtensive PubMed search to see whether RP and another set of driver genes not yet reported (NR) to be mutated in endometriosis have any roles in fibrogenesis. All studies reporting on the role of fibrogenesis of the genes in both RP and NR sets were retrieved and evaluated in this review.ResultsAll six RP genes were involved in various aspects of fibrogenesis as compared with only three NR genes. These nine genes can be anchored in networks linking with their upstream and downstream genes that are known to be aberrantly expressed in endometriosis, piecing together seemingly unrelated findings.ConclusionsGiven that somatic driver mutations can and do occur frequently in physiologically normal tissues, it is argued that these mutations in endometriosis are not necessarily synonymous with malignancy or premalignancy, but the result of enormous pressure for fibrogenesis.

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“…Endometriosis is a gynecological disorder affecting 10% to 15% of women in reproductive age; up to 70% of the patients have pelvic pain and 48% have fertility problems [1,2]. The disease is characterized by the presence of stromal and/or endometrial glandular epithelium outside the uterus and is classified in three different types: superficial, ovarian and deep endometriosis [3][4][5]. Endometriosis was first described in the seventeenth century and, despite all research efforts in the last 30 years, its pathogenesis is still unclear [6].…”

Section: Introductionmentioning

confidence: 99%

Microbiome Profile of Deep Endometriosis Patients: Comparison of Vaginal Fluid, Endometrium and Lesion

Hernandes

Silveira²,

Sereia³

et al. 2020

Diagnostics

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This work aimed to identify and compare the bacterial patterns present in endometriotic lesions, eutopic endometrium and vaginal fluid from endometriosis patients with those found in the vaginal fluid and eutopic endometrium of control patients. Vaginal fluid, eutopic endometrium and endometriotic lesions were collected. DNA was extracted and the samples were analyzed to identify microbiome by high-throughput DNA sequencing of the 16S rRNA marker gene. Amplicon sequencing from vaginal fluid, eutopic endometrium and endometriotic lesion resulted in similar profiles of microorganisms, composed most abundantly by the genus Lactobacillus, Gardnerella, Streptococcus and Prevotella. No significant differences were found in the diversity analysis of microbiome profiles between control and endometriotic patients; however deep endometriotic lesions seems to present different bacterial composition, less predominant of Lactobacillus and with more abundant Alishewanella, Enterococcus and Pseudomonas.

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Deep Invasive Endometriosis Lesions of the Rectosigmoid May Be Related to Alterations in Cell Kinetics

Abstract: Changes in cell proliferation but not in the AI in rectosigmoid endometriosis are indicative of an imbalance in cell kinetics that may lead to the development of the disease.

Cited by 9 publications

References 36 publications

TOP2A deficit-induced abnormal decidualization leads to recurrent implantation failure via the NF-κB signaling pathway

TOP2A deficit-induced abnormal decidualization leads to recurrent implantation failure via the NF-κB signaling pathway

Cancer driver mutations in endometriosis: Variations on the major theme of fibrogenesis

Microbiome Profile of Deep Endometriosis Patients: Comparison of Vaginal Fluid, Endometrium and Lesion

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