Zearalenone (ZEA) is one of the common mycotoxins in feeds. ZEA and its metabolites have estrogen-like activity and can competitively bind to estrogen receptors, causing reproductive dysfunction and damage to reproductive organs. The toxicity mechanism of ZEA mainly inhibits the antioxidant pathway and antioxidant enzyme activity, induces cell cycle arrest and DNA damage, and blocks the process of cellular autophagy to produce toxic effects. In animal husbandry practice, when animals ingest ZEA-contaminated feed, it is likely to lead to abortion in females, abnormal sperm viability in males with inflammatory reactions in various organs, and cancerous changes in the reproductive organs of humans when they ingest contaminated animal products. In this paper, we reviewed in detail how ZEA induces oxidative damage by inducing the generation of reactive oxygen species (ROS) and regulating the expression of genes related to oxidative pathways, induces germ cell apoptosis through the mitochondrial and death receptor pathways, and activates the expression of genes related to autophagy in order to induce cellular autophagy. In addition, the molecular detoxification mechanism of ZEA is also explored in this paper, aiming to provide a new direction and theoretical basis for the development of new ZEA detoxification methods to better reduce the global pollution and harm caused by ZEA.

The sex-specific prevalence of adrenal diseases has been known for a long time. However, the reason for the high prevalence of these diseases in females is not completely understood. Mouse studies have shown that the adult adrenal gland is sexually dimorphic at different levels such as transcriptome, histology, and cell renewal. Here we used RNA-seq to show that in prepubertal mice, male and female adrenal glands were not only sexually dimorphic but also responded differently to the same external stimulus. We previously reported that thyroid hormone receptor β1 (TRβ1) in the adrenal gland is mainly expressed in the inner cortex and the fate of this TRβ1-expressing cell population can be changed by thyroid hormone (triiodothyronine; T3) treatment. In the present study, we found that adrenal glands in prepubertal mice were sexually dimorphic at the level of the transcriptome. Under T3 treatment, prepubertal females had 1162 genes differentially expressed between the saline and T3 groups, whereas in males of the same age, only 512 genes were T3-responsive. Immunostaining demonstrated that several top sexually dimorphic T3-responsive genes, including Cyp2f2 and Dhcr24, were specifically expressed in the adrenal inner cortex, precisely in an area partially overlapping with the X-zone. Under T3 treatment, a unique cortical layer that surrounds the adrenal X-zone expanded significantly, forming a distinct layer peculiar to females. Our findings identified novel marker genes for the inner adrenal cortex, indicating there are different sub-zones in the zona fasciculata. The results also highlight the sex-specific response to thyroid hormone in the mouse adrenal gland.

Zearalenone (ZEA) is a mycotoxin produced by Fusarium spp. fungi and is widely found in moldy corn, wheat, barley, and other grains. ZEA is distributed to the whole body via blood circulation after metabolic transformation in animals. Through oxidative stress, immunosuppression, apoptosis, autophagy, and mitochondrial dysfunction, ZEA leads to hepatitis, neurodegenerative diseases, cancer, abortion, and stillbirth in female animals, and decreased sperm motility in male animals. In recent years, due to the influence of climate, storage facilities, and other factors, the problem of ZEA pollution in global food crops has become particularly prominent, resulting in serious problems for the animal husbandry and feed industries, and threatening human health. Resveratrol (RSV) is a natural product with therapeutic activities such as anti-inflammatory, antioxidant, and anticancer properties. RSV can alleviate ZEA-induced toxic effects by targeting signaling pathways such as NF-κB, Nrf2/Keap1, and PI3K/AKT/mTOR via attenuating oxidative damage, inflammatory response, and apoptosis, and regulating cellular autophagy. Therefore, this paper provides a review of the protective effect of RSV against ZEA-induced toxicity and its molecular mechanism, and discusses the safety and potential clinical applications of RSV in the search for natural mycotoxin detoxification agents.

Zearalenone (ZEA), a prevalent mycotoxin in moldy feeds, induces apoptosis by disrupting cellular homeostasis, leading to multi-organ damage, particularly in the kidneys, intestines, and reproductive system. Selenomethionine (SeMet), a natural amino acid with antioxidant and anticancer properties, was investigated for its protective effects against ZEA-induced nephrotoxicity. In this study, rabbits were exposed to ZEA and varying concentrations of SeMet, followed by renal tissue analysis. Pathological examination revealed significant structural damage in ZEA-treated kidneys, including glomerular atrophy, fibrosis, impaired glycogenolysis, and inflammatory injury due to dysregulated pro-inflammatory and anti-inflammatory factor expression. Mechanistically, ZEA suppressed PI3K/Akt/mTOR signaling, triggering excessive autophagy initiation but impairing autophagic flux, ultimately disrupting cellular homeostasis. This dysregulation upregulated pro-apoptotic proteins (Cyt C, Caspase-3, Caspase-9) while downregulating Bcl-2, exacerbating renal apoptosis. SeMet supplementation counteracted these effects by restoring PI3K/Akt/mTOR pathway activity, normalizing autophagy, and rebalancing apoptotic protein expression. Notably, 0.35 mg/kg SeMet demonstrated optimal renal protection. These findings highlight SeMet's potential as a dietary supplement to mitigate ZEA-induced kidney injury via modulation of autophagy and apoptosis pathways.