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患子宫内膜异位症母马的子宫肌层转录组变化。

The myometrial transcriptome changes in mares with endometrosis.

作者信息

Drzewiecka Ewa Monika, Molcan Tomasz, Sadowska Agnieszka, Piotrowska-Tomala Katarzyna, Słyszewska Magda, Dias Graça Ferreira, Skarżyński Dariusz Jan, Szóstek-Mioduchowska Anna

机构信息

Institute of Animal Reproduction and Food Research, Polish Academy of Sciences in Olsztyn, 10-748, Olsztyn, Poland.

Molecular Biology Laboratory, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences in Olsztyn, 10-748, Olsztyn, Poland.

出版信息

Sci Rep. 2025 Jan 25;15(1):3173. doi: 10.1038/s41598-025-86742-0.

DOI:10.1038/s41598-025-86742-0
PMID:39863666
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11762791/
Abstract

Mares with endometrosis exhibit histological changes not only in the endometrium but also in the myometrium that suggest possible functional impairment. The molecular background of these changes is not well understood. We hypothesize that the transcriptomic profile of the mare myometrium varies depending on the degree of endometrosis in mares. Myometria were collected from mares in the mid-luteal phase of the estrous cycle with endometrium categories I, IIA, IIB, and III (∑n = 23), according to Kenney and Doig´s histopathological classification. Myometrial RNA was isolated and subjected to RNA-seq analysis to identify differentially expressed transcriptionally active regions (deTARs) and their contribution to signaling pathways (KEGG database) and biological processes (GO terms). In results, 665, 491 and 499 deTARs were found in the myometrium of mares with endometrium IIA vs I, IIB vs I and III vs I, respectively. 200 common deTARs in the myometrium across all stages of endometrosis (IIA, IIB, and III) vs I were identified. Evaluated deTARs enriched several KEGG pathways including calcium signaling, cAMP signaling, oxytocin signaling, ECM-receptor interaction, and focal adhesion, and were classified into various GO terms including adaptive immune response, tissue homeostasis, muscle contractions, muscle development, and other. In conclusion, transcriptomic alterations in the myometrium of mares with endometrosis may indicate an impaired function of the contractile machinery, mechanisms regulating calcium influx and handling, as well as changes in ECM composition, leading to a decreased contractile activity and structural changes in the myometrium of affected mares.

摘要

患有子宫内膜异位症的母马不仅子宫内膜会出现组织学变化,子宫肌层也会出现此类变化,这表明可能存在功能受损。这些变化的分子背景尚不清楚。我们推测,母马子宫肌层的转录组图谱会因母马子宫内膜异位症的程度而异。根据肯尼和多伊格的组织病理学分类,在发情周期的黄体中期从患有I、IIA、IIB和III类子宫内膜的母马身上采集子宫肌层(n = 23)。分离子宫肌层RNA并进行RNA测序分析,以鉴定差异表达的转录活性区域(deTAR)及其对信号通路(KEGG数据库)和生物学过程(GO术语)的贡献。结果发现,在患有IIA期与I期、IIB期与I期以及III期与I期子宫内膜的母马子宫肌层中,分别发现了665个、491个和499个deTAR。确定了在子宫内膜异位症所有阶段(IIA、IIB和III期)与I期的子宫肌层中共有200个deTAR。评估的deTAR丰富了几种KEGG通路,包括钙信号传导、cAMP信号传导、催产素信号传导、ECM-受体相互作用和粘着斑,并被分类为各种GO术语,包括适应性免疫反应、组织稳态、肌肉收缩、肌肉发育等。总之,患有子宫内膜异位症的母马子宫肌层的转录组改变可能表明收缩机制功能受损、调节钙内流和处理的机制以及ECM组成发生变化,导致受影响母马子宫肌层的收缩活性降低和结构改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f8/11762791/3042bc22646c/41598_2025_86742_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f8/11762791/c5f4c401b2b1/41598_2025_86742_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f8/11762791/f46403e659d0/41598_2025_86742_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f8/11762791/9e0572737d4c/41598_2025_86742_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f8/11762791/a03910e4fcf9/41598_2025_86742_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f8/11762791/28004c85aaea/41598_2025_86742_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f8/11762791/3042bc22646c/41598_2025_86742_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f8/11762791/c5f4c401b2b1/41598_2025_86742_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f8/11762791/f46403e659d0/41598_2025_86742_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f8/11762791/9e0572737d4c/41598_2025_86742_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f8/11762791/a03910e4fcf9/41598_2025_86742_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f8/11762791/28004c85aaea/41598_2025_86742_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8f8/11762791/3042bc22646c/41598_2025_86742_Fig6_HTML.jpg

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本文引用的文献

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Eur J Pharmacol. 2024 Apr 5;968:176343. doi: 10.1016/j.ejphar.2024.176343. Epub 2024 Jan 26.
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PGF induces a pro-labour phenotypical switch in human myometrial cells that can be inhibited with PGF receptor antagonists.前列腺素F(PGF)可诱导人子宫肌层细胞发生促分娩表型转换,而这种转换可被PGF受体拮抗剂抑制。
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The physiological basis with uterine myometrium contractions from electro-mechanical/hormonal myofibril function to the term and preterm labor.
从电机械/激素肌原纤维功能到足月和早产时子宫肌层收缩的生理基础。
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Transcriptomic profiling of mare endometrium at different stages of endometrosis.转录组谱分析马子宫内膜在子宫内膜异位症不同阶段的变化。
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The potential role of miRNAs and regulation of their expression in the development of mare endometrial fibrosis.miRNAs 的潜在作用及其在母马子宫内膜纤维化发展中的表达调控。
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