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、附睾和精囊的显著组织学改变。与对照组相比，暴露于全氟辛烷磺酸（PFOS）和全氟辛酸盐（PFOA）的雄性大鼠睾丸组织中的氧化应激（OS）标记物（如丙二醛（MDA））水平明显更高。此外，免疫组织化学显示，与对照组相比，PFOS和PFOA组的OS标记物MDA、4-羟基壬烯醛（4-HNE）和8-羟基鸟苷（8-OHdG）的表达显著升高。此外，在交配研究之后，与全氟辛烷磺酸或暴露于全氟辛烷磺酸的雄性大鼠交配的雌性大鼠所生的新生儿存活率明显低于对照组。在4周的记录期内，PFOS组和PFOA组新生儿的体重均显著低于对照组。目前，第一代被观察和跟踪，直到新的交配研究进行，所以我们可以评估对第二代的影响。此外，将通过分析精子DNA甲基化来研究第一代的表观遗传。在本研究的发现中，一个突出的发现是暴露于pfc的大鼠产生的精子的强烈受精后效应。大鼠精子中pfc引起的DNA损伤是如此强烈，以至于影响了新生儿的生存。