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.

本项目研究的雄性大鼠暴露于全氟化学品（PFCs）的影响导致睾丸、附睾和精囊发生显著的组织学改变。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的氧化应激（OS）标志物（如丙二醛（MDA））水平显著升高。此外，免疫组织化学显示，与对照组相比，全氟辛烷磺酸和全氟辛酸组的OS标志物MDA、4-羟基壬烯醛（4-HNE）和8-羟基鸟苷（8-OHdG）的表达明显较高。此外，交配研究后，与接触全氟辛烷磺酸或全氟辛酸的雄性大鼠交配的雌性大鼠所产下的新生儿存活率明显低于对照组。此外，在为期4周的记录期间，PFOS和PFOA组新生儿的体重明显低于对照组新生儿。目前，对第一代进行了观察和随访，直到进行新的交配研究，因此我们可以评估对第二代的影响。此外，第一代的表观遗传将通过分析精子DNA甲基化来研究。在本研究的发现中，一个突出的发现是暴露于PFCs的大鼠产生的精子的强烈的受精后效应。PFCs对大鼠精子的DNA损伤是如此强烈，以至于影响新生儿的存活。

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.