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Proteomic analysis of the eutopic endometrium of patients with internal or external ademomyosis

ABSTRACT: Adenomyosis is a common benign gynecological condition causing abnormal uterine bleeding, dysmenorrhea, chronic pelvic pain, as well as infertility . Histologically, adenomyosis is defined by the presence of ectopic endometrial glands and stroma surrounded by hypertrophic and hyperplastic myometrium . Recent studies have defined two distinct phenotypes of adenomyosis based on the location of adenomyotic lesions within the myometrium: either predominantly in the inner layer (internal adenomyosis) or more confined to the outer layer (external adenomyosis) . Patients with external and internal adenomyosis phenotypes present radiological and clinical-demographic differences (. Although the exact etiology of the disease remains debated, some authors suggest that internal adenomyosis results from endometrial invasion or de novo from metaplasia of embryonic or adult stem cell transformation within the myometrium, while external adenomyosis may occur through invasion from adjacent endometriotic lesions or from differentiation of endometrial stem cells deposited during retrograde menstruation. In this work we compare the protein expression profile of the endometria of patients with either internal or external adenomyosis using a DIA-based label free approach.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Uterine Endometrium

DISEASE(S): Endometriosis Of Uterus

SUBMITTER: Mikel Azkargorta

LAB HEAD: Felix Elortza

PROVIDER: PXD055131 | Pride | 2025-01-14

REPOSITORIES: pride

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			Action	DRS
	231110_231019A_MValdes_10_S1-A10_1_11830.RAW	Raw
	231110_231019A_MValdes_11_S1-A11_1_11831.RAW	Raw
	231110_231019A_MValdes_12_S1-A12_1_11832.RAW	Raw
	231110_231019A_MValdes_13_S1-B1_1_11833.RAW	Raw
	231110_231019A_MValdes_14_S1-B2_1_11834.RAW	Raw

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Project description:Abstract: Objective: Adenomyosis is a clinical disorder defined by the presence of endometrial glands and stroma within the myometrium, the pathogenesis of which is poorly understood. We postulate that dysregulation of genes and pathways in eutopic endometrium may predispose to ectopic implantation. No study, to our knowledge, has examined the global transcriptome of isolated eutopic endometrium from women with clinically significant adenomyosis. Design: Laboratory-based study with full IRB approval and consents. Material and Methods: Endometrial sampling was performed on hysterectomy specimens (proliferative phase) from symptomatic women with pathologically-confirmed diffuse adenomyosis (n=3). Controls (n=5) were normo-ovulatory subjects without adenomyosis. All subjects were free from leiomyoma, endometriosis, and hormonal exposures. Isolated purified total RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway analysis. Validation of several genes was undertaken by QRT-PCR. Results: Comparison of transcriptomes of proliferative endometrium from women with and without adenomyosis revealed 140 up-regulated and 884 down-regulated genes in samples from women with adenomyosis compared to controls. Highly differentially expressed genes include those involved in regulation of apoptopsis, steroid hormone responsiveness, and proteins involved in extracellular matrix remodeling, as well as microRNAs of unknown significance. Affected canonical pathways included eukaryotic initiation factor 2 signaling, oxidative phosphorylation, mitochondrial dysfunction, estrogen receptor signaling, and mTOR signaling. Conclusions: The eutopic endometrium in patients with adenomyosis has fundamental abnormalities that may predispose to invasion and survival beyond the myometrial interface. Key Words: adenomyosis, endometrium, microarray, microRNA, endometriosis, apoptosis, signaling. Abstract: Objective: Adenomyosis is a clinical disorder defined by the presence of endometrial glands and stroma within the myometrium, the pathogenesis of which is poorly understood. We postulate that dysregulation of genes and pathways in eutopic endometrium may predispose to ectopic implantation. No study, to our knowledge, has examined the global transcriptome of isolated eutopic endometrium from women with clinically significant adenomyosis. Design: Laboratory-based study with full IRB approval and consents. Material and Methods: Endometrial sampling was performed on hysterectomy specimens (proliferative phase) from symptomatic women with pathologically-confirmed diffuse adenomyosis (n=3). Controls (n=5) were normo-ovulatory subjects without adenomyosis. All subjects were free from leiomyoma, endometriosis, and hormonal exposures. Isolated purified total RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway analysis. Validation of several genes was undertaken by QRT-PCR. Results: Comparison of transcriptomes of proliferative endometrium from women with and without adenomyosis revealed 140 up-regulated and 884 down-regulated genes in samples from women with adenomyosis compared to controls. Highly differentially expressed genes include those involved in regulation of apoptopsis, steroid hormone responsiveness, and proteins involved in extracellular matrix remodeling, as well as microRNAs of unknown significance. Affected canonical pathways included eukaryotic initiation factor 2 signaling, oxidative phosphorylation, mitochondrial dysfunction, estrogen receptor signaling, and mTOR signaling. Conclusions: The eutopic endometrium in patients with adenomyosis has fundamental abnormalities that may predispose to invasion and survival beyond the myometrial interface. Key Words: adenomyosis, endometrium, microarray, microRNA, endometriosis, apoptosis, signaling. A total of 8 samples were used and analyzed by disease state. Endometrial samples from hysterectomy specimens in proliferative phase of menstrual cycle from symptomatic women with pathologically-confirmed diffuse adenomyosis were compared with endometrial samples from normo-ovulatory healthy subjects with no endometrial or uterine pathology.

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Proteomic analysis of the eutopic endometrium of patients with internal or external ademomyosis

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