Kimberley E Sala-Hamrick, Kai Wang, Bambarendage P U Perera, Maureen A Sartor, Laurie K Svoboda, Dana C Dolinoy
{"title":"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。","authors":"Kimberley E Sala-Hamrick, Kai Wang, Bambarendage P U Perera, Maureen A Sartor, Laurie K Svoboda, Dana C Dolinoy","doi":"10.1080/15592294.2025.2542879","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2542879"},"PeriodicalIF":3.2000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341058/pdf/","citationCount":"0","resultStr":"{\"title\":\"Sex-stratified piRNA expression analysis reveals shared functional impacts of perinatal lead (Pb) exposure in murine hearts.\",\"authors\":\"Kimberley E Sala-Hamrick, Kai Wang, Bambarendage P U Perera, Maureen A Sartor, Laurie K Svoboda, Dana C Dolinoy\",\"doi\":\"10.1080/15592294.2025.2542879\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":11767,\"journal\":{\"name\":\"Epigenetics\",\"volume\":\"20 1\",\"pages\":\"2542879\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341058/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Epigenetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/15592294.2025.2542879\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/10 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epigenetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/15592294.2025.2542879","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/10 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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.
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