性别分层piRNA表达分析揭示围产期铅(Pb)暴露对小鼠心脏功能的共同影响。

IF 3.2 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-08-10 DOI:10.1080/15592294.2025.2542879
Kimberley E Sala-Hamrick, Kai Wang, Bambarendage P U Perera, Maureen A Sartor, Laurie K Svoboda, Dana C Dolinoy
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引用次数: 0

摘要

piwi相互作用RNA (piRNA)在心脏中的表达情况尚不清楚,特别是在性别差异方面。piRNA表达改变在心血管疾病(CVD)中有报道,尽管暴露于金属铅(Pb)与CVD风险密切相关,但没有研究调查Pb对心脏piRNA的影响。本研究旨在表征小鼠心脏中piRNA的表达,并评估与人类相关的母体铅暴露对成年后代心脏piRNA表达的性别特异性影响。使用高碘酸钠排除小RNA并随后测序从整个小鼠心脏中鉴定pirna。对照组小鼠在性别分析中表达了18956个pirna;性别特异性分析显示,女性心脏中有9231个pirna,男性心脏中有5972个pirna。基因组图谱显示,28-41%与内含子一致,12-28%与外显子一致。比较对照组和铅暴露心脏,我们发现女性(847)比男性(187)有更多潜在的铅诱导表达变化(p值1)。这些pirna在涉及心脏功能和心血管疾病发展相关生物过程的基因附近显著富集,包括线粒体功能、能量代谢和心肌结构(FDR)
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sex-stratified piRNA expression analysis reveals shared functional impacts of perinatal lead (Pb) exposure in murine hearts.

The landscape of PIWI-interacting RNA (piRNA) expression in the heart is poorly understood, particularly regarding sex differences. Altered piRNA expression has been reported in cardiovascular disease (CVD), and although exposure to the metal lead (Pb) is strongly associated with CVD risk, no studies have investigated Pb's effects on cardiac piRNAs. This study aimed to characterize piRNA expression in the murine heart and assess sex-specific effects of human-relevant maternal Pb exposure on adult offspring cardiac piRNA expression. piRNAs were identified from whole mouse hearts using sodium periodate exclusion of small RNA and subsequent sequencing. Control mice expressed 18,956 piRNAs in combined-sex analysis; sex-specific analyses revealed 9,231 piRNAs in female hearts and 5,972 piRNAs in male hearts. Genomic mapping showed 28-41% aligned to introns, while 12-28% mapped to exons. Comparing control and Pb-exposed hearts, we found more potential Pb-induced expression changes in females (847) compared to males (187) (p-value < 0.05 and |logFC| > 1). These piRNAs were significantly enriched near genes involved in biological processes related to heart function and CVD development, including mitochondrial function, energy metabolism, and cardiac muscle structure (FDR < 0.05). Overall, we characterized combined and sex-stratified piRNA expression in both control and Pb-exposed murine hearts. In addition to providing a foundation for sex-specific piRNA expression in the heart, these findings suggest a novel epigenetic mechanism by which developmental Pb exposure may impact CVD risk later in life. Future studies will link these sex-specific molecular changes to Pb-induced alterations in cardiac function.

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来源期刊
Epigenetics
Epigenetics 生物-生化与分子生物学
CiteScore
6.80
自引率
2.70%
发文量
82
审稿时长
3-8 weeks
期刊介绍: Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed. Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to): DNA methylation Nucleosome positioning and modification Gene silencing Imprinting Nuclear reprogramming Chromatin remodeling Non-coding RNA Non-histone chromosomal elements Dosage compensation Nuclear organization Epigenetic therapy and diagnostics Nutrition and environmental epigenetics Cancer epigenetics Neuroepigenetics
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