Male infertility and perfluoroalkyl and poly-fluoroalkyl substances: evidence for alterations in phosphorylation of proteins and fertility-related functional attributes in bull spermatozoa†.

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Arumugam Kumaresan, Pankaj Yadav, Manish Kumar Sinha, Pradeep Nag, Ebenezer Samuel King John Peter, Jay S Mishra, Sathish Kumar
{"title":"Male infertility and perfluoroalkyl and poly-fluoroalkyl substances: evidence for alterations in phosphorylation of proteins and fertility-related functional attributes in bull spermatozoa†.","authors":"Arumugam Kumaresan, Pankaj Yadav, Manish Kumar Sinha, Pradeep Nag, Ebenezer Samuel King John Peter, Jay S Mishra, Sathish Kumar","doi":"10.1093/biolre/ioae089","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Perfluoroalkyl and poly-fluoroalkyl substances (PFAS) are pervasive environmental pollutants and potential threats to reproductive health. Epidemiological studies have established an association between PFAS and male infertility, but the underlying mechanisms are unclear.</p><p><strong>Objectives: </strong>Investigate the effect of perfluorooctane sulfonic acid (PFOS), the most prevalent and representative PFAS, on bull sperm protein phosphorylation and function.</p><p><strong>Methods: </strong>We exposed bull sperm to PFOS at 10 (average population exposure) and 100 μM (high-exposure scenario), and analyzed global proteomic and phosphoproteomic analysis by TMT labeling and Nano LC-MS/MS. We also measured sperm fertility functions by flow cytometry.</p><p><strong>Results: </strong>PFOS at 10-μM altered sperm proteins linked to spermatogenesis and chromatin condensation, while at 100 μM, PFOS affected proteins associated with motility and fertility. We detected 299 phosphopeptides from 116 proteins, with 45 exhibiting differential expression between control and PFOS groups. PFOS dysregulated phosphorylation of key proteins (ACRBP, PRKAR2A, RAB2B, SPAG8, TUBB4B, ZPBP, and C2CD6) involved in sperm capacitation, acrosome reaction, sperm-egg interaction, and fertilization. PFOS also affected phosphorylation of other proteins (AQP7, HSBP9, IL4I1, PRKAR1A, and CCT8L2) related to sperm stress resistance and cryotolerance. Notably, four proteins (PRM1, ACRBP, TSSK1B, and CFAP45) exhibited differential regulation at both proteomic and phosphoproteomic levels. Flow cytometric analysis confirmed that PFOS increased protein phosphorylation in sperm and also decreased sperm motility, viability, calcium, and mitochondrial membrane potential and increased mitochondrial ROS in a dose-dependent manner.</p><p><strong>Conclusions: </strong>This study demonstrates that PFOS exposure negatively affects phosphorylation of proteins vital for bull sperm function and fertilization.</p>","PeriodicalId":3,"journal":{"name":"ACS Applied Electronic Materials","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402523/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Electronic Materials","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/biolre/ioae089","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, ELECTRICAL & ELECTRONIC","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Perfluoroalkyl and poly-fluoroalkyl substances (PFAS) are pervasive environmental pollutants and potential threats to reproductive health. Epidemiological studies have established an association between PFAS and male infertility, but the underlying mechanisms are unclear.

Objectives: Investigate the effect of perfluorooctane sulfonic acid (PFOS), the most prevalent and representative PFAS, on bull sperm protein phosphorylation and function.

Methods: We exposed bull sperm to PFOS at 10 (average population exposure) and 100 μM (high-exposure scenario), and analyzed global proteomic and phosphoproteomic analysis by TMT labeling and Nano LC-MS/MS. We also measured sperm fertility functions by flow cytometry.

Results: PFOS at 10-μM altered sperm proteins linked to spermatogenesis and chromatin condensation, while at 100 μM, PFOS affected proteins associated with motility and fertility. We detected 299 phosphopeptides from 116 proteins, with 45 exhibiting differential expression between control and PFOS groups. PFOS dysregulated phosphorylation of key proteins (ACRBP, PRKAR2A, RAB2B, SPAG8, TUBB4B, ZPBP, and C2CD6) involved in sperm capacitation, acrosome reaction, sperm-egg interaction, and fertilization. PFOS also affected phosphorylation of other proteins (AQP7, HSBP9, IL4I1, PRKAR1A, and CCT8L2) related to sperm stress resistance and cryotolerance. Notably, four proteins (PRM1, ACRBP, TSSK1B, and CFAP45) exhibited differential regulation at both proteomic and phosphoproteomic levels. Flow cytometric analysis confirmed that PFOS increased protein phosphorylation in sperm and also decreased sperm motility, viability, calcium, and mitochondrial membrane potential and increased mitochondrial ROS in a dose-dependent manner.

Conclusions: This study demonstrates that PFOS exposure negatively affects phosphorylation of proteins vital for bull sperm function and fertilization.

男性不育与全氟烷基和多氟烷基物质:公牛精子中蛋白质磷酸化和生育相关功能属性改变的证据。
背景:全氟烷基和多氟烷基物质(PFAS)是一种普遍存在的环境污染物,也是影响生殖健康的新风险因素。尽管流行病学证据支持这些物质与男性不育之间存在联系,但人们对它们对男性生育能力的具体影响仍然知之甚少:调查全氟辛烷磺酸(PFOS)(最普遍、最常见的全氟辛烷磺酸)对公牛精子蛋白质磷酸化的影响,磷酸化是精子功能和生育能力的翻译后修饰过程:我们将公牛精子暴露于 10 μM(平均人群水平)和 100 μM(高暴露水平)的全氟辛烷磺酸中,并通过 TMT 标记和 NanoLC-MS/MS 分析了全蛋白质组和磷酸化蛋白质组的概况。我们还通过流式细胞术测量了精子的生育功能:结果:10 μM 的全氟辛烷磺酸会改变与精子发生和染色质凝聚有关的精子蛋白质,而 100 μM 的全氟辛烷磺酸则会影响与活力和生育力有关的蛋白质。我们从 116 个蛋白质中检测到 299 个磷酸肽,其中 45 个在对照组和全氟辛烷磺酸组之间有差异表达。PFOS 使参与精子获能、顶体反应、精卵相互作用和受精的关键蛋白(ACRBP、PRKAR2A、RAB2B、SPAG8、TUBB4B、ZPBP 和 C2CD6)的磷酸化失调。全氟辛烷磺酸还影响了与精子抗应激性和低温耐受性有关的其他蛋白质(AQP7、HSBP9、IL4I1、PRKAR1A 和 CCT8L2)的磷酸化。值得注意的是,有 4 种蛋白质(PRM1、ACRBP、TSSK1B 和 CFAP45)在蛋白质组和磷酸化蛋白质组水平上表现出不同的调控。流式细胞分析证实,全氟辛烷磺酸增加了精子中的蛋白质磷酸化,降低了精子活力、存活率、钙和膜电位,并以剂量依赖的方式增加了线粒体 ROS:这项研究表明,接触全氟辛烷磺酸会对对公牛精子功能和受精至关重要的蛋白质磷酸化产生不利影响。此外,全氟辛烷磺酸的浓度会影响这些影响的严重程度。本研究中全面的公牛精子磷酸化蛋白质组学数据有助于我们了解与环境暴露相关的男性不育症的分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信