We investigated the potential ability of quercetin to protect against lipopolysaccharide (LPS)-induced intestinal oxidative stress in broiler chickens and the potential role of the Nrf2 (nuclear factor erythroid 2-related factor 2) signaling pathway. One-day-old broiler chickens (n = 240) were randomized into four groups: saline-challenged broiler chickens fed a basal diet (Con), LPS-challenged broiler chickens on a basal diet (LPS), and LPS-treated broiler chickens on a basal diet containing either 200 or 500 mg/kg of quercetin (Que200+LPS or Que500+LPS). Quercetin (200 mg/kg) significantly alleviated LPS-induced decreased duodenal, jejunal, and illeal villus height and increased the crypt depth in these regions. Quercetin significantly inhibited LPS-induced jejunal oxidative stress, including downregulated reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels, and it upregulated superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. Quercetin relieved LPS-induced jejunal mitochondria damage and upregulated mitochondrial DNA copy number-related gene expression, including cytochrome c oxidase subunit 1 (COX1), ATP synthase F0 subunit 6 (ATP6), and NADH dehydrogenase subunit 1 (ND1). Quercetin attenuated the LPS-induced inhibition of Nrf2 activation, translocation, and downstream gene expression, including heme oxygenase-1 (HO-1), NAD (P) H dehydrogenase quinone 1 (NQO1), and manganese superoxide dismutase (SOD2). Additionally, quercetin attenuated the LPS-inhibition of c-Jun N-terminal kinase (JNK), Extracellular Regulated protein Kinases (ERK), and p38MAPK (p38) phosphorylation in the MAPK pathway. Thus, quercetin attenuated LPS-induced oxidative stress in the intestines of broiler chickens via the MAPK/Nrf2 signaling pathway.

Oxidative-stress-induced apoptosis of granulosa cells is considered to be a main driver of follicular atresia. Increasing evidence suggests a protective effect of melatonin against oxidative damage but the mechanism remains unclear. The aim of this study is to investigate the effects of melatonin on mitophagy and apoptosis of bovine ovarian granulosa cells under oxidative stress, and to clarify the mechanism. Our results indicate that melatonin inhibited H₂O₂-induced apoptosis and mitochondrial injury of bovine ovarian granulosa cells, as revealed by decreased apoptosis rate, reactive oxygen species (ROS) levels, Ca²⁺ concentration, and cytochrome C release and increased mitochondrial membrane potential (ΔΨm). Simultaneously, melatonin promoted mitophagy of bovine ovarian granulosa cells through increasing the expression of PTEN-induced putative kinase 1 (PINK1), PARKIN, BECLIN1, and LC3II/LC3I; decreasing the expression of sequestosome 1 (SQSMT1); and promoting mitophagosome and lysosome fusion. After treatment with a mitophagy inhibitor CsA, we found that melatonin alleviated apoptosis and mitochondrial injury through promoting mitophagy in bovine ovarian granulosa cells. Furthermore, melatonin promoted the expression of silent information regulator 1 (SIRT1) and decreased the expression level of forkhead transcription factors class O (type1) (FoxO1). By treatment with an SIRT1 inhibitor EX527 or FoxO1 overexpression, the promotion of melatonin on mitophagy as well as the inhibition on mitochondrial injury and apoptosis were reversed in bovine ovarian granulosa cells. In conclusion, our results suggest that melatonin could promote mitophagy to attenuate oxidative-stress-induced apoptosis and mitochondrial injury of bovine ovarian granulosa cells via the SIRT1/FoxO1 signaling pathway.

There are microbial communities in and on the bodies of all multicellular organisms, and this microbiota can have a significant impact on the biology of the host. Most studies have focused on the microbiome of the skin, mouth, and gut, whereas relatively little is known about the reproductive microbiome. From the perspective of the bovine reproductive tract, uterine diseases such as metritis and endometritis are traditionally viewed to result only from interactions occurring between the host animal and pathogens originating from either the environment or ascension from the vagina. This outdated opinion has been refuted by recent advanced studies that propose that, in addition to bacteria colonization through the extrinsic and ascending pathways to the vagina, bacteria can also move from the gut to the uterus, which is also associated with reproductive tract disorders. This has led to the concept of the “endogenous route hypothesis”, which has vital inferences for comprehending the etiology of metritis and endometritis. Furthermore, it has opened up the possibility of developing new prophylactic and therapeutic agents as alternatives to antimicrobial agents. In addition, the unveiling of next-generation sequencing technology makes it more convenient to perform detailed sequencing and analysis of data on the cervical, vaginal, and uterine flora and to further study uncultured bacteria in these niches—most importantly, the cervical niche, which previously was thought to have lower bacterial complexity. Research conducted to date has proven that the composition of microflora in a community varies widely between environmental sites, host niches, and health status. Furthermore, it has also been suggested that the occurrence of endometritis in the dairy and beef cattle reproductive tract is neither casual nor indirect but multifactorial. Whether disturbance in the variety of the microflora in the reproductive tract (dysbiosis) has a role in determining the sensitivity to metritis and endometritis is not yet known. This article outlines the current progress in understanding the microflora with regards to the bovine reproductive tract. The compositions of microflora in various niches of the reproductive tract are briefly elucidated. In addition, the functional role of these microflora communities in the reproductive tract is discussed, with particular emphasis on the association of bacterial flora with reproductive disorders and failures. Finally, prophylaxis and therapeutic approaches based on the new comprehension of the effects of antimicrobials, probiotics, and bacteriophages on the composition of the reproductive tract microflora are also considered.