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

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.