The in vitro maturation efficiency of porcine oocytes is relatively low, and this limits the production of in vitro porcine embryos. Since melatonin is involved in mammalian reproductive physiology, in this study, we have explored whether endogenously produced melatonin can help in porcine oocyte in vitro maturation. We have found, for the first time in the literature, that mitochondria are the major sites for melatonin biosynthesis in porcine oocytes. This mitochondrially originated melatonin reduces ROS production and increases the activity of the mitochondrial respiratory electron transport chain, mitochondrial biogenesis, mitochondrial membrane potential, and ATP production. Therefore, melatonin improves the quality of oocytes and their in vitro maturation. In contrast, the reduced melatonin level caused by siRNA to knockdown AANAT (siAANAT) is associated with the abnormal distribution of mitochondria, decreasing the ATP level of porcine oocytes and inhibiting their in vitro maturation. These abnormalities can be rescued by melatonin supplementation. In addition, we found that siAANAT switches the mitochondrial oxidative phosphorylation to glycolysis, a Warburg effect. This metabolic alteration can also be corrected by melatonin supplementation. All these activities of melatonin appear to be mediated by its membrane receptors since the non-selective melatonin receptor antagonist Luzindole can blunt the effects of melatonin. Taken together, the mitochondria of porcine oocytes can synthesize melatonin and improve the quality of oocyte maturation. These results provide an insight from a novel aspect to study oocyte maturation under in vitro conditions.

Protein arginine methylation is a posttranslational modification catalyzed by protein arginine methyltransferases (PRMTs), which play critical roles in many biological processes. To date, nine PRMT family members, namely, PRMT1, 2, 3, 4, 5, 6, 7, 8, and 9, have been identified in mammals. Among them, PRMT7 is a type III PRMT that can only catalyze the formation of monomethylarginine and plays pivotal roles in several kinds of stem cells. It has been reported that PRMT7 is closely associated with embryonic stem cells, induced pluripotent stem cells, muscle stem cells, and human cancer stem cells. PRMT7 deficiency or mutation led to severe developmental delay in mice and humans, which is possibly due to its crucial functions in stem cells. Here, we surveyed and summarized the studies on PRMT7 in stem cells and development in mice and humans and herein provide a discussion of the underlying molecular mechanisms. Furthermore, we also discuss the roles of PRMT7 in cancer, adipogenesis, male reproduction, cellular stress, and cellular senescence, as well as the future perspectives of PRMT7-related studies. Overall, PRMT7 mediates the proliferation and differentiation of stem cells. Deficiency or mutation of PRMT7 causes developmental delay, including defects in skeletal muscle, bone, adipose tissues, neuron, and male reproduction. A better understanding of the roles of PRMT7 in stem cells and development as well as the underlying mechanisms will provide information for the development of strategies for in-depth research of PRMT7 and stem cells as well as their applications in life sciences and medicine.

In this study, we have investigated potential roles of cholestasis played in spermatogenesis in the cholestatic animal model generated by giving the mice DDC diet. The data showed that cholestasis jeopardized the testicular structure and function by downregulating the expressions of genes related to the androgen's synthesis. Mechanistically, the cholestasis disturbers the liver's tryptophan metabolism and its metabolites. These tryptophan metabolites including serotonin, 5-Hydroxyindoleacetic acid, 4-(2-Aminophenyl)-2,4-dioxobutanoic acid and Quinoline-4,8-diol were significantly reduced in the cholestatic mice model compared to their controlled counterparts. These tryptophan metabolites are the endogenous ligands of AHR and their levels are positively correlated to the expressions of genes related to the androgen's synthesis and AHR. Notably, supplementation of AHR ligand ITE promoted the expression of genes related to the testosterone synthesis and alleviated abnormal spermatogenesis. In addition, the bacteria that disturbed the tryptophan metabolism in cholestatic mice were identified by 16S rDNA sequencing and Spearman correlation analysis. Briefly, we have identified a cholestasis associated gut microbiota-testis axis. This axis is responsible for the cholestasis induced abnormal spermatogenesis and male reproductive dysfunction. Breaking vicious cycle of this axis may be a suitable strategy to prevent and treat the cholestasis associated male infertility.

As the global climate changes, high temperatures will cause heat stress, which significantly affects the productive efficiency of livestock. Currently, there is a lack of efficient methods to use in targeting this issue. In this study, we report that melatonin supplementation may represent an alternative method to reduce the negative impact of heat stress on livestock, particularly in Hainan black goats. Our results show that melatonin treatment increased the average daily gain of Hainan black goats that were exposed to constantly high temperatures for two months compared to controls. Our mechanistic exploration revealed that melatonin treatment not only reduced the oxidative stress and inflammatory reaction caused by heat stress but also improved goats’ metabolic capacity, promoting their growth and development. More importantly, for the first time, we observed that melatonin treatment modified the abundance of the intestinal microflora, altering the metabolism of the goats, which further improved their tolerance to constant heat stress.

The mycotoxin zearalenone (ZEN), commonly found in contaminated food and feed, poses a significant threat to human and animal health, particularly to reproductive function. Mitigating its toxicity represents a critical research priority in food safety. Apigenin (AP) is a naturally occurring dietary flavonoid with phytoestrogenic properties and exhibits diverse pharmacological activities. In this study, we investigated the protective effects of AP against ZEN-induced apoptosis and oxidative stress in Swine Testis (ST) cells and elucidated its underlying mechanisms. The identity of ST cells was verified via RT-PCR and agarose gel electrophoresis. ST cells were treated with 40 μM ZEN and 1 μM and 0.1 μM AP for 24 h. Cell viability was detected via CCK8 and EdU assays, cytotoxicity was evaluated via LDH assay, cell cycle and apoptosis levels were analyzed via flow cytometry, and the mechanism by which AP alleviated the damage caused by ZEN to ST cells was preliminarily revealed using RNA-Seq technology. Further, the expression levels of related genes and proteins were detected by qRT-PCR and Western blot. Our results show that 1 μM or 0.1 μM AP effectively attenuated the cytotoxicity induced by 40 μM ZEN in ST cells, as evidenced by restored cell viability, reduced the LDH level, normalized cell cycle progression, reduced apoptotic rates, and enhanced antioxidant capacity. RNA-Seq analysis was coupled with molecular validation and used to elucidate the mechanisms underlying AP-mediated protection against ZEN-induced cellular injury. It is shown that ZEN suppressed the expression of LRP5, a pivotal gene in the Wnt signaling pathway, along with its downstream effector c-Myc. Conversely, treatment with 1 μM or 0.1 μM AP upregulated the expression of LRP5, iASPP, and TRAF2 at both transcriptional and translational levels. Importantly, the protective effects of AP were abrogated with IWR-1-endo, a specific Wnt pathway inhibitor, confirming pathway dependency. Collectively, our findings show that AP alleviates ZEN-induced oxidative stress and apoptosis in ST cells through the upregulation of LRP5 and subsequent activation of the Wnt signaling pathway. This study provides molecular evidence supporting the potential clinical application of AP as a preventive agent against ZEN-induced reproductive toxicity.

In dairy cow, the peripartum metabolic stage is critical as may affect post-partum metabolic and reproductive recovery, colostrum quality, and overall reproductive fitness. This study aimed to evaluate the effects of varying doses of α-ketoglutarate (AKG) on lactation performance, reproductive performance, immune function, and antioxidant capacity in periparturient dairy cows. A total of 180 periparturient dairy cows were randomly assigned to four groups, with each cow receiving 1 g, 5 g, or 10 g of AKG in their prepartum diets. Results indicated that feeding 5 g and 10 g of AKG significantly increased the colostrum fat and protein content, reduced somatic cell counts, and improved daily milk yield. Regarding reproduction, AKG supplementation regulated reproductive hormones, increased postpartum estrogen levels, improved conception rates, and shortened the interval between breeding periods. For immune and antioxidant functions, AKG significantly increased serum IL-10 levels while reducing TNF-α and interleukins 1β and 6. It also significantly elevated glutathione peroxidase (GSH-PX) levels, reducing oxidative stress and demonstrating anti-inflammatory and immunomodulatory effects. Additionally, cows receiving medium-to-high doses of AKG had a significantly lower incidence of postpartum diseases such as mastitis. In conclusion, appropriate AKG supplementation can improve lactation performance, reproductive performance, immune function, and overall health in periparturient dairy cows, providing a theoretical basis for its use in dairy cow nutrition management.