Kieran Brennan, Raminta Vaiciuleviciute, Ilona Uzieliene, Jolita Pachaleva, Zaneta Kasilovskiene, Lina Piesiniene, Eiva Bernotiene, Margaret M Mc Gee
{"title":"Menstrual blood serum extracellular vesicles reveal novel molecular biomarkers and potential endotypes of unexplained infertility.","authors":"Kieran Brennan, Raminta Vaiciuleviciute, Ilona Uzieliene, Jolita Pachaleva, Zaneta Kasilovskiene, Lina Piesiniene, Eiva Bernotiene, Margaret M Mc Gee","doi":"10.1038/s41598-025-95818-w","DOIUrl":null,"url":null,"abstract":"<p><p>Several biomolecules have been previously associated with unexplained infertility (uIF) in blood and uterine samples, immune cells and their secreted factors, endometrial tissue, menstrual blood, serum, and stromal cells, however they do not comprehensively represent different uIF endotypes and their isolation/detection involves invasive diagnostic methods and lacks precision. This ex-vivo study was performed on extracellular vesicles (EVs) from menstrual blood collected on cycle day 2 from 9 fertile volunteers and 8 women with uIF. Menstrual blood serum (MBS) EVs were isolated from fertile and uIF MBS using Iodixanol Density Gradient Centrifugation and quantified by flow cytometry. EVs were characterized according to MISEV2023 guidelines. Comprehensive proteomic analysis of MBS EVs and EV-depleted MBS showed significant changes in uIF proteome, mostly affecting cell adhesion, immune response, apoptosis, response to oxidative stress and lipid metabolism. These processes were previously linked to pathologies of the female reproductive system but never investigated in uIF and were used to stratify patients into distinct molecular endotypes. Area under the curve (AUC) analysis was used to determine the optimum set of biomarkers for each of the uIF molecular endotypes. These findings provide new insights into uIF that could facilitate personalised treatment approaches.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"11974"},"PeriodicalIF":3.8000,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Scientific Reports","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41598-025-95818-w","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Several biomolecules have been previously associated with unexplained infertility (uIF) in blood and uterine samples, immune cells and their secreted factors, endometrial tissue, menstrual blood, serum, and stromal cells, however they do not comprehensively represent different uIF endotypes and their isolation/detection involves invasive diagnostic methods and lacks precision. This ex-vivo study was performed on extracellular vesicles (EVs) from menstrual blood collected on cycle day 2 from 9 fertile volunteers and 8 women with uIF. Menstrual blood serum (MBS) EVs were isolated from fertile and uIF MBS using Iodixanol Density Gradient Centrifugation and quantified by flow cytometry. EVs were characterized according to MISEV2023 guidelines. Comprehensive proteomic analysis of MBS EVs and EV-depleted MBS showed significant changes in uIF proteome, mostly affecting cell adhesion, immune response, apoptosis, response to oxidative stress and lipid metabolism. These processes were previously linked to pathologies of the female reproductive system but never investigated in uIF and were used to stratify patients into distinct molecular endotypes. Area under the curve (AUC) analysis was used to determine the optimum set of biomarkers for each of the uIF molecular endotypes. These findings provide new insights into uIF that could facilitate personalised treatment approaches.
期刊介绍：
We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections.
Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021).
•Engineering
Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live.
•Physical sciences
Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics.
•Earth and environmental sciences
Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems.
•Biological sciences
Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants.
•Health sciences
The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
