The accumulation of microplastics (MPs) within the environment caused serious ecological and health problems. Nevertheless, its systemic toxicity to organisms and its mechanisms lack effective evidence. This study established a model of MP exposure through the gavage of polystyrene (PS)-MPs particles to maternal mice on days 1 to 21 of lactation. The results demonstrated that PS-MPs were distributed widely in maternal mice, occurring mainly in the feces, colon, liver and mammary glands. Further experiments revealed that the gut and blood-milk barriers were disrupted, and pathological injury and inflammatory reactions were observed in the liver, gut, and mammary glands. Metabolomic and metagenome analysis indicated abnormalities in hepatic bile acid metabolism and significant alterations in the gut microbiota after exposure to PS-MPs. These alterations led to increased disruption of the intestine-liver axis. Notably, with fecal microbiota transplantation and antibiotic experiments, we observed that elimination of the intestinal microbiota reduced tissue inflammation and improved gut and blood-milk barrier leakage. These findings demonstrated that PS-MPs exaggerated intestine-liver axis disorders by inducing colonic injury, intestinal ecological dysregulation and abnormal hepatic bile acid metabolism. Furthermore, PS-MPs translocated via the intestine-liver axis and exerted broader toxic effects on mammary tissue. Overall, our study uncovered the transfer toxicity of PS-MPs in mice, proposing the possibility of a gut-liver-mammary axis.

The endometrium undergoes a series of complex changes to form a receptive endometrium (RE) that allows the embryo to be implanted. The inability to establish endometrial receptivity of livestock causes embryo implantation failure and considerable losses to animal husbandry. MicroRNAs (miRNAs) are a class of noncoding RNAs. Studies have found that miRNAs can regulate many critical physiological processes, including the establishment of RE during embryo implantation. miR-184 is highly expressed in the endometrial receptive period of dairy goats. This study aimed to explore the effect of miR-184 on endometrial epithelial cell (EEC) apoptosis and RE establishment. Stanniocalcin2 (STC2) is a direct target of miR-184, and miR-184 decreases the expression of STC2 in dairy goat EECs. miR-184 can activate EECs apoptosis through the RAS/RAF/MEK/ERK pathway. Additionally, miR-184 increases the expression levels of RE marker genes, such as forkhead box M1 (FOXM1) and vascular endothelial growth factor (VEGF). These findings indicate that miR-184 promotes the apoptosis of endometrial epithelial cells in dairy goats by downregulating STC2 via the RAS/RAF/MEK/ERK pathway, and that it may also regulate the establishment of RE in dairy goats.

The accumulation of ovarian granulosa cell (GC) apoptosis underlies follicular atresia. By comparing the previous sequencing results, miR-486 was found to be differentially expressed at higher levels in the monotocous goat than in the polytocous goat. Unfortunately, the miRNA-mediated mechanisms by which the GC fate is regulated are unknown in Guanzhong dairy goats. Therefore, we investigated miR-486 expression in small and large follicles, as well as its impact on normal GC survival, apoptosis and autophagy in vitro. Here, we identified and characterized miR-486 interaction with Ser/Arg-rich splicing factor 3 (SRSF3) using luciferase reporter analysis, detecting its role in GC survival, apoptosis and autophagy regulation through qRT-PCR, Western blot, CCK-8, EdU, flow cytometry, mitochondrial membrane potential and monodansylcadaverine, etc. Our findings revealed prominent effects of miR-486 in the regulation of GC survival, apoptosis and autophagy by targeting SRSF3, which might explain the high differential expression of miR-486 in the ovaries of monotocous dairy goats. In summary, this study aimed to reveal the underlying molecular mechanism of miR-486 regulation on GC function and its effect on ovarian follicle atresia in dairy goats, as well as the functional interpretation of the downstream target gene SRSF3.

Curcumin, a natural polyphenol with well-established antioxidant and anti-inflammatory properties, was evaluated for its protective effects against glyphosate (GLY)-induced mammary toxicity. Pregnant mice received GLY (50 or 250 mg/kg/day) with or without curcumin (150 mg/kg/day) by oral gavage; GLY dose-dependently disrupted alveolar architecture, caused marked inflammatory infiltration, and downregulated tight-junction proteins. In parallel, goat mammary epithelial cells (GMECs) were treated with GLY (1 or 7 mM) and curcumin (1 µM) to dissect acute cellular stress pathways. These complementary models address distinct aspects of GLY toxicity: the in vivo system reflects defined oral exposure, whereas the in vitro setting employs high concentrations to probe mechanistic events. Transcriptomic profiling combined with functional assays demonstrated that GLY triggered oxidative stress, endoplasmic reticulum stress, and intracellular Ca²⁺ overload, activated the TNFα/MAPK axis, suppressed STAT3 phosphorylation, and ultimately promoted apoptosis. Curcumin co-treatment alleviated these alterations at both structural and molecular levels. These findings indicate that curcumin can combat GLY-induced mammary injury by restoring cellular homeostasis and inhibiting apoptotic and inflammatory signaling, thereby protecting breast health.