Bisphenol F-Associated Repeated Breeding Syndrome in Cows: Epidemiological Evidence and Protective Effects of...

Repeat breeding syndrome (RBS), characterized by repeated artificial insemination failure, is associated with ovarian dysfunction in ruminants and causes economic losses. Environmental endocrine-disrupting chemicals (EDCs), such as bisphenol F (BPF), may contribute to RBS, but the relationship between BPF exposure and RBS in cows remains unclear. In this study, we conducted an epidemiological investigation and clinical examinations in 111 adult Simmental cows, including 7 cows diagnosed with RBS, from two local farms, and measured the BPF levels in the drinking water, feed, and the serum samples. We further evaluated the protective effects of phillyrin, a bioactive compound derived from Forsythia suspensa, against BPF-induced ovarian toxicity using cow granulosa cells (CGCs). RBS mainly occurred in young cows with two or more parities. RBS cows showed signs of potential liver dysfunction, kidney injury, anemia, and fecal abnormalities suggestive of altered gut health, together with higher serum BPF levels and lower estradiol levels. Detectable BPF contamination in the drinking water and feed suggested environmental exposure as a possible contributor to RBS in cows. In vitro, BPF induced inflammatory and apoptotic responses in CGCs by upregulating pro-inflammatory and pro-apoptotic mediators, whereas phillyrin pretreatment markedly alleviated these effects. These findings suggest that BPF exposure might be associated with RBS in cows and phillyrin could be used as a promising natural agent for mitigating BPF-related reproductive toxicity.