The revelation of the mechanism of the post-fertilization effect of paternal exposure on endocrine disruptors on the development and fertilizing capacity of the male offspring.

揭示父本暴露内分泌干扰物的受精后效应对雄性子代发育和受精能力的影响机制。

• 批准号: 20K18092
• 负责人: ツナピ パナイオタ
• 金额: $ 2.66万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2020
• 资助国家: 日本
• 起止时间: 2020-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20K18092/
• 关键词: pefluorinated chemicals; male infertility; testis; sperm; oxidative stress; epigenetic inheritance; endocrine disruptor; perfluorinated chemicals; male gamete; mitochondria; post-fertilization

The effects of perfluorinated chemicals (PFCs) exposure of male rats that were investigated in this project resulted in significant histological alterations in the testis, epididymis and seminal vesicles. The levels of oxidative stress (OS) markers, such as malondialdehyde (MDA) were significantly higher in the testicular tissue of male rats that were exposed to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) compared to the Control group. Furthermore, immunohistochemistry demonstrated significantly high expression of OS markers MDA, 4-hydroxynonenal (4-HNE) and 8-hydroxyguanosine (8-OHdG) in the PFOS and PFOA groups compared to the Control group.Additionally, after mating studies, the newborns that were delivered from female rats that mated with PFOS or PFOA-exposed male rats had significantly low survival rate compared to the Control group. Moreover the body weight of the PFOS and PFOA group newborns was significantly lower compared to the Control group newborns during all the recording period which lasted 4 weeks.Currently the 1st generation is observed and followed up until new mating studies are performed so we can evaluate the effects on the 2nd generation. Additionally the epigenetic inheritance in the first generation will be investigated by analyzing spermatozoa DNA methylation.Among the findings of the present study, one that stands out is the strong post-fertilization effect of the spermatozoa that were produced by rats exposed to PFCs. The DNA damage that is induced by PFCs in the rat sperm is so strong that affects the survival of the newborns.

本项目研究的雄性大鼠接触全氟化学品 (PFC) 的影响导致睾丸、附睾和精囊发生显着的组织学改变。与对照组相比，暴露于全氟辛烷磺酸（PFOS）和全氟辛酸（PFOA）的雄性大鼠睾丸组织中氧化应激（OS）标志物（例如丙二醛（MDA））的水平显着升高。此外，免疫组织化学显示，与对照组相比，PFOS 和 PFOA 组中 OS 标志物 MDA、4-羟基壬烯醛 (4-HNE) 和 8-羟基鸟苷 (8-OHdG) 的表达显着升高。此外，经过交配研究，雌性大鼠与暴露于 PFOS 或 PFOA 的雄性大鼠交配所产下的新生儿 与对照组相比，存活率明显较低。此外，在长达 4 周的记录期内，PFOS 和 PFOA 组新生儿的体重显着低于对照组新生儿。目前对第一代进行观察和随访，直到进行新的交配研究，以便我们评估对第二代的影响。此外，还将通过分析精子 DNA 甲基化来研究第一代的表观遗传。在本研究的结果中，最引人注目的是暴露于 PFC 的大鼠产生的精子的强烈受精后效应。 PFC 在大鼠精子中引起的 DNA 损伤非常严重，会影响新生儿的存活。