雄性在受孕前暴露于玉米赤霉烯酮会损害小鼠的雄性生育能力并降低体外受精胚胎的存活率

Preconception paternal exposure to zearalenone impairs male fertility and IVF embryo survival in mice

雄性在受孕前暴露于玉米赤霉烯酮会损害小鼠的雄性生育能力并降低体外受精胚胎的存活率

Authors:Peiwen Wang,Yaxin Chen,Yuan Jiao,Yating Zhu,Mengyao Wang,Dongmei Ji,Weiwei Zou,Yunxia Cao,Yajing Liu,Dan Liang

Source:Chemico-biological Interactions

PMID:40681136

DOI:10.1016/j.cbi.2025.111646

Abstract

Zearalenone (ZEA), a fungal mycotoxin commonly found in various human foods, exhibits a structural similarity to naturally occurring estrogen, raising significant concerns regarding its reproductive toxicity. This study aimed to assess the impact of preconceptional ZEA exposure on male reproductive health and early embryonic development. Healthy B6D2F1 male mice were exposed to corn oil or varying doses of ZEA for two weeks. Our findings revealed that ZEA exposure caused a notable reduction in sperm count and motility, accompanied by significant weight loss in the high-dose group. Additionally, high-dose ZEA exposure induced oxidative stress, mitochondrial dysfunction, and activation of the ERK and p38 MAPK signaling pathways. Furthermore, preconception paternal exposure to ZEA adversely affected in vitro fertilization (IVF) outcomes. Specifically, male mice exposed to high-dose ZEA exhibited significantly reduced fertilization rates and impaired embryonic development, resulting in embryonic arrest. Metabolic assessment of blastocysts demonstrated elevated levels of reactive oxygen species (ROS) and a pronounced decrease in mitochondrial membrane potential (MMP), indicating compromised developmental potential in blastocysts derived from sperm of ZEA-exposed males. In conclusion, this study highlights that high-dose ZEA exposure induces testicular damage, disrupts mitochondrial function, impairs early embryo quality post-IVF, and activates the p38/ERK MAPK signaling pathway.

Keywords: Apoptosis; Embryo development; MAPK signaling pathway; Mitochondrial dynamics; Zearalenone.

摘要

玉米赤霉烯酮(ZEA）是一种常见于多种人类食物中的真菌毒素，其结构与天然雌激素相似，因此引发了对其生殖毒性的严重担忧。本研究旨在评估孕前ZEA暴露对雄性生殖健康及早期胚胎发育的影响。健康B6D2F1雄性小鼠被分为两组，分别暴露于玉米油或不同剂量的ZEA，持续两周。研究结果显示，ZEA暴露导致精子数量和活力显著下降，高剂量组小鼠还伴随明显体重减轻。此外，高剂量ZEA暴露诱发氧化应激、线粒体功能障碍，并激活ERK和p38 MAPK信号通路。进一步研究发现，孕前父代ZEA暴露对体外受精(IVF）结果产生不利影响。具体而言，高剂量ZEA暴露的雄性小鼠表现出显著降低的受精率和受精后胚胎发育受损，导致胚胎停滞。对囊胚的代谢评估显示，活性氧(ROS）水平升高及线粒体膜电位(MMP）显著下降，表明来自ZEA暴露雄性精子的囊胚发育潜能受损。综上所述，本研究表明高剂量ZEA暴露会引起睾丸损伤、扰乱线粒体功能、影响IVF后早期胚胎质量，并激活p38/ERK MAPK信号通路。

关键词：凋亡；胚胎发育；MAPK信号通路；线粒体动态；玉米赤霉烯酮