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苯并(a)芘诱导的小鼠精子DNA损伤模型的转录组学和蛋白质组学特征

Transcriptomic and proteomic features of a mouse model of sperm DNA damage induced by benzo(a)pyrene.

作者信息

Zhang Chenming, Ma Yunfeng, Liu Wenbang, Ma Sicheng, Chen Zhelin, Hao XiaoHui, Sun Zixue, Wang Zulong

机构信息

Henan University of Chinese Medicine, Zhengzhou, Henan 450046, China; The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan 450003, China.

Henan University of Chinese Medicine, Zhengzhou, Henan 450046, China.

出版信息

Reprod Toxicol. 2024 Jun;126:108596. doi: 10.1016/j.reprotox.2024.108596. Epub 2024 Apr 17.

DOI:10.1016/j.reprotox.2024.108596
PMID:38641015
Abstract

This study replicated a mouse model of sperm DNA damage induced by benzo(a)pyrene (BaP), and the transcriptomic and proteomic features of the model were examined to clarify the pathways related to BaP-induced damage to sperm DNA. Male mice in the BaP group were subjected to BaP at a dosage of 100 mg/kg/d or an equivalent quantity of saline solution in the control group for 60 days. Subsequently, the DNA fragmentation index (DFI) in sperm was assessed using a sperm chromatin structure assay (SCSA). RNA-seq and data-independent acquisition (DIA) were used to identify the mRNA and protein expression patterns in the testis. The sperm DFI significantly increased in the BaP group. Compared to the control group, the BaP group exhibited differential expression of 240 genes (referred to as DEGs) and 616 proteins (referred to as DEPs). These molecules included Aldh1a1, Cyb5r3, Fads1, Oxsm, Rcn3, and Prss45. Pathways in cancer, the PI3K-Akt signaling pathway, metabolic pathways, and the MAPK signaling pathway were the primary areas where these genes showed enrichment. BaP can damage the DNA of sperm and affect metabolism, the PI3K-Akt pathway, and pathways associated with cancer signaling.

摘要

本研究复制了苯并(a)芘(BaP)诱导的小鼠精子DNA损伤模型,并检测了该模型的转录组和蛋白质组特征,以阐明与BaP诱导的精子DNA损伤相关的途径。BaP组雄性小鼠每天接受100 mg/kg的BaP处理,对照组接受等量的盐溶液处理,持续60天。随后,使用精子染色质结构分析(SCSA)评估精子中的DNA碎片化指数(DFI)。采用RNA测序和数据非依赖采集(DIA)技术鉴定睾丸中的mRNA和蛋白质表达模式。BaP组精子DFI显著升高。与对照组相比,BaP组有240个基因(称为差异表达基因,DEGs)和616种蛋白质(称为差异表达蛋白,DEPs)表达存在差异。这些分子包括醛脱氢酶1A1(Aldh1a1)、细胞色素b5还原酶3(Cyb5r3)、脂肪酸去饱和酶1(Fads1)、氧化应激诱导跨膜蛋白(Oxsm)、富含半胱氨酸的分泌蛋白3(Rcn3)和丝氨酸蛋白酶45(Prss45)。癌症相关通路、PI3K-Akt信号通路、代谢通路和MAPK信号通路是这些基因显示富集的主要区域。BaP可损伤精子DNA,并影响代谢、PI3K-Akt通路以及与癌症信号相关的通路。

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