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 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.

Milk-production is one of the most important economic traits in dairy goats. Fundamentally, increasing milk-production at the genetic level can provide potential genetic markers for improving milk-production in dairy goats. Previous studies have shown that milk-production traits in dairy goats are highly polygenic and can be influenced by multiple genes. We therefore performed high-throughput sequencing on 350 Saanen dairy goats and conducted a genome-wide association study (GWAS) on the sequencing and production data. A total of 9,667,930 valid SNPs were identified, among which approximately 51% of the mutations were synonymous changes, and apart from unknown mutations, only a few changes affected gene expression. Finally, 318 SNP loci and 244 candidate genes were selected. We selected 10 loci most likely to influence these traits for large-scale population-based identification. Finally, four candidate genes, CDC14A, F11, RBPJL and ZFAND2A, were identified as the most likely to affect milk-production traits in dairy goats. To prevent spurious association analyses, we conducted subsequent experiments. Further results showed that the four candidate genes could regulate the proliferation and secretion of dairy goat mammary epithelial cells by regulating MAPK, mTOR and other pathways. These findings provide more valuable genetic markers and a theoretical basis for better understanding the intrinsic mechanisms of dairy goat mammary glands.