Crosstalk between trace elements and T-cell immunity during early-life health in pigs.

With gradual ban on the use of antibiotics, the deficiency and excessive use of trace elements in intestinal health is gaining attention. In mammals, trace elements are essential for the development of the immune system, specifically T-cell proliferation, and differentiation. However, there remain significant gaps in our understanding of the effects of certain trace elements on T-cell immune phenotypes and functions in pigs. In this review, we summarize the specificity, development, subpopulations, and responses to pathogens of porcine T cells and the effects of functional trace elements (e.g., iron, copper, zinc, and selenium) on intestinal T-cell immunity during early-life health in pigs. Furthermore, we discuss the current trends of research on the crosstalk mechanisms between trace elements and T-cell immunity. The present review expands our knowledge of the association between trace elements and T-cell immunity and provides an opportunity to utilize the metabolism of trace elements as a target to treat various diseases.

Identification of Candidate Genes for Min Pig Villi Hair Traits by Genome-Wide Association of Copy Number Variation.

The Min pig is a famous native pig breed in northeast China, which has the special genetic character of villi hair growth in cold seasons. At present, little research has focused on the genetic mechanism of villi hair growth in Min pigs. Copy number variations (CNVs) are a type of variant that may influence many traits. In this study, we first investigated the phenotype of Large White × Min pigs' F2 pig villi hair in detail and then performed a CNV-based genome-wide association study (GWAS) between CNVs and pig villi hair appearance. Finally, a total number of 15 significant CNVRs were found to be associated with Min pig villi hair. The most significant CNVR was located on chromosome 1. Nearest gene annotation analysis indicated that the pig villi hair traits may be associated with the biological process of the G-protein-coupled receptor signaling pathway. QTL overlapping analysis found that among the CNVRs, 14 CNVRs could be co-located with known QTLs. Some genes such as MCHR2, LTBP2, and GFRA2 may be candidate genes for pig villi traits and are worth further study. Our study may provide a basic reference for the selection and breeding of cold-resistant pigs and outdoor breeding.

Characterization of Growth Secondary Hair in Min Pig Activated by Follicle Stem Cell Stimulated by Wnt and BMP Signaling Pathway.

In China, the national-level protected pig, the Min pig, is characterized by the development of secondary hairs and hair follicles in winter. Factors that dominate the genotype in the growth of secondary hairs are not clear through the concrete cell signaling pathways. This study compared hair phenotypes based on morphological structure, transcriptomics, and potential targeting molecules in the breeds of Min, Berkshire, and Yorkshire pigs. The results indicated that Min pigs have specific characteristics for the growth of secondary hairs compared with the Berkshire and Yorkshire pigs. The transcriptome analyses and quantitative reverse transcription-polymerase chain reaction results revealed that secondary hair growth was activated by follicle stem cells. The specific inhibitors of Wnt and BMP were studied using respective signals. The density of follicles, activity of follicle stem cells, and relative gene expression results have shown that Wnt and BMP stimulate the activity of follicle stem cells, and the Wnt signaling molecule has a significantly better effect than the BMP signaling molecule on stem cells. Wnt and BMP can promote the growth of local secondary hair and gene expression. Therefore, this study was conducted to verify the development mechanisms of secondary hairs, which have potential applications in laboratory animals and comparative medicine.

Transcriptome Analysis Reveals Genes Contributed to Min Pig Villi Hair Follicle in Different Seasons.

The Min pig, a local pig breed in China, has a special trait which has intermittent villus and coat hair regeneration. However, the regulation and mechanism of villus in Min pigs have not yet been described. We observed and described the phenotype of Min pig dermal villi in detail and sequenced the mRNA transcriptome of Min pig hair follicles. A total of 1520 differentially expressed genes (DEG) were obtained.K-means hierarchical clustering showed that there was a significant expression pattern difference in winter compared with summer. Gene enrichment and network analysis results showed that the hair growth in Min pigs was closely related to the composition of desmosomes and regulated by an interaction network composed of eight core genes, namely DSP, DSC3, DSG4, PKP1, TGM1, KRT4, KRT15, and KRT84. Methylation analysis of promoters of target genes showed that the PKP1 gene was demethylated. Our study will help to supplement current knowledge of the growth mechanism of different types of hair.

Removal of antibiotic resistance genes and mobile genetic elements in a three-stage pig manure management system: The implications of microbial community structure.

In this work, the removal of antibiotic resistance genes (ARGs) in the industrial-scale pig manure management system has been investigated. Additionally, the implications of mobile genetic elements (MGEs) and microbial community structure have been discussed. During the whole period of manure management, 19 ARGs and 7 MGEs were obtained from the system. The results identified that the 9 ARGs and 2 MGEs were removed from the pig manure-based materials after composting, while 5 ARGs and 2 MGEs were still remained, indicating that the ARGs/MGEs could not be removed completely as contaminants by composting. The pig farm without additional antibiotics in-feed was still faced with the risk of ARGs/MGEs from outside. Microbial community analysis illuminated that a greater decrease in the abundance of norank_f__JG30-KF-CM45, Corynebacterium, Terrisporobacter, Truepera, Salinispora and Clostridium, was responsible for the removal of ARGs/MGEs. The genes, including tnpA-01, tnpA-02, tnpA-05, Tp614, tetQ, tetM-01, tetR-02, tetX, cfxA, floR, dfrA1 and ermF exhibited significantly positive correlation with fungal communities. Fungal community analysis verified that a remarkable decrease in the abundance of Aspergillus and Thermomyces after composting was responsible for the ARGs/MGEs removal. The results elucidated the crucial roles of the related bacterial and fungal communities in the removal of ARGs/MGEs. The compound microbial agent assisted the temperature rise of composting, thereby changing the related microbial community structure and resulting in ARGs/MGEs removal.

Improvement of Ulcerative Colitis by Aspartate via RIPK Pathway Modulation and Gut Microbiota Composition in Mice.

The intestine requires a great deal of energy to maintain its health and function; thus, energy deficits in the intestinal mucosa may lead to intestinal damage. Aspartate (Asp) is an essential energy source in the intestinal mucosa and plays a vital part in gut health. In the current study, we hypothesized that dietary supplementation of Asp could alleviate DSS-induced colitis via improvement in the colonic morphology, oxidative stress, cell apoptosis, and microbiota composition in a mouse model of dextran. Asp administration decreased the disease activity index, apoptosis, myeloperoxidase, eosinophil peroxidase, and proinflammatory cytokine (IL-1ß and TNF-α) concentrations in the colonic tissue, but improved the body weight, average daily food intake, colonic morphology, and antioxidant-related gene (GPX1 and GPX4) expression in DSS-treated mice. Expression levels of RIPK1 and RIPK3 were increased in the colon following Asp administration in the DSS-induced mice, whereas the MLKL protein expression was decreased. 16S rRNA sequencing showed that Asp treatment increased the abundance of Lactobacillus and Alistipes at the gene level, and Bacteroidetes at the phylum level, but decreased the abundance of Actinobacteria and Verrucomicrobia at the phylum level. Asp may positively regulate the recovery of DSS-induced damage by improving the immunity and antioxidative capacity, regulating RIPK signaling and modulating the gut microbiota composition.

Ferroptosis and Its Multifaceted Role in Cancer: Mechanisms and Therapeutic Approach.

Ferroptosis, a new type of non-apoptotic cell death modality, is different from other modes of cell death and has been primarily found in tumor cells. Previous studies have reported that ferroptosis can be triggered by specific modulators (e.g., drugs, nutrients, and iron chelators), leading to increased intracellular lipid reactive oxygen species (ROS) accumulation and iron overload. Recent reports have shown that ferroptosis at the cellular and organism levels can prevent an inflammatory storm and cancer development. Emerging evidence suggests potential mechanisms (e.g., system Xc-, glutathione peroxidase 4 (GPX4), lipid peroxidation, glutathione (GSH), and iron chelators) are involved in ferroptosis, which may mediate biological processes such as oxidative stress and iron overload to treat cancer. To date, there are at least three pathways that mediate ferroptosis in cancer cells: system Xc-/GSH/GPX4, FSP1/CoQ10/NAD(P)H, and ATG5/ATG7/NCOA4. Here, we summarize recent advances in the occurrence and development of ferroptosis in the context of cancer, the associations between ferroptosis and various modulators, and the potential mechanisms and therapeutic strategies targeting ferroptosis for the treatment of cancer.

Glutamine in suppression of lipopolysaccharide-induced piglet intestinal inflammation: The crosstalk between AMPK activation and mitochondrial function.

The study was conducted to investigate the regulatory mechanism of glutamine (Gln) on intestinal inflammation in an Escherichia coli lipopolysaccharide (E. coli LPS)-induced in vivo and in vitro models. Piglets (n = 8) weaned at 21 d of age were fed a basal diet (control and LPS groups) or 1% Gln diet (Gln + LPS group) ad libitum for 4 weeks. On d 22, 24, 26 and 28, piglets in the LPS and Gln + LPS groups were intraperitoneally injected with E. coli LPS. Intestinal porcine epithelial cells (IPEC-J2) (n = 6) induced by LPS were used to assess related mechanisms and compound C was used to inhibit adenosine 5'-monophosphate-activated protein kinase (AMPK) activity. Our current results showed that compared with the LPS treatment, the Gln + LPS treatment had better growth performance and greater villus height (P < 0.05), and the Gln + LPS treatment reduced the rate of diarrhea by 6.4% (P < 0.05); the Gln + LPS treatment decreased serum tumor necrosis factor (TNF-ɑ), interleukin-6 (IL-6), K+, cortisol and insulin levels, whereas increased (P < 0.05) serum immunoglobulin M and epidermal growth factor levels; the Gln + LPS treatment increased (P < 0.05) the expression of aquaporins and AMPK pathway-associated targets in the jejunum and ileum of piglets, whereas decreased the expression of ion transporters (P < 0.05). The in vitro results showed that 4 mmol/L Gln administration could inhibit (P < 0.05) cell apoptosis and interleukin-1ß (IL-1ß), IL-6 and TNF-ɑ secretion in LPS-induced IPEC-J2 cells, promote (P < 0.05) mitochondrial respiratory metabolism and increase (P < 0.05) the number of mitochondria and mitochondrial membrane potential. The activity of AMPK was elevated by 70% to 300% in Gln-treated IPEC-J2 cells under LPS challenge or normal conditions. Our results indicate that pre-administration of Gln to piglets suppresses intestinal inflammation by modulating the crosstalk between AMPK activation and mitochondrial function.

Mycotoxins in livestock feed in China - Current status and future challenges.

Mycotoxins are toxic metabolites or secondary metabolites produced by fungi and exist widely in all kinds of food and feed raw materials. They have led to many poisoning events and brought huge economic losses to livestock and poultry breeders every year. At present, the main challenges in the field of feed mycotoxin prevention and control are the high contamination rate, high coexistence rate, high detection cost and lagging research and development of prevention and control technology. Based on research data and results published by Chinese scholars in academic journals at home and abroad in recent years, this paper summarizes the status and causes of mycotoxin contamination in different feeds in China. At the same time, problems exist in the detection of mycotoxin contamination in Chinese feed. It is hoped to provide guidelines for the prevention and control of mycotoxin contamination.

A global meta-analysis of animal manure application and soil microbial ecology based on random control treatments.

The processes involved in soil domestication have altered the soil microbial ecology. We examined the question of whether animal manure application affects the soil microbial ecology of farmlands. The effects of global animal manure application on soil microorganisms were subjected to a meta-analysis based on randomized controlled treatments. A total of 2303 studies conducted in the last 30 years were incorporated into the analysis, and an additional 45 soil samples were collected and sequenced to obtain 16S rRNA and 18S rRNA data. The results revealed that manure application increased soil microbial biomass. Manure application alone increased bacterial diversity (M-Z: 7.546 and M-I: 8.68) and inhibited and reduced fungal diversity (M-Z: -1.15 and M-I: -1.03). Inorganic fertilizer replaced cattle and swine manure and provided nutrients to soil microorganisms. The soil samples of the experimental base were analyzed, and the relative abundances of bacteria and fungi were altered compared with no manure application. Manure increased bacterial diversity and reduced fungal diversity. Mrakia frigida and Betaproteobacteriales, which inhibit other microorganisms, increased significantly in the domesticated soil. Moreover, farm sewage treatments resulted in a bottleneck in the manure recovery rate that should be the focus of future research. Our results suggest that the potential risks of restructuring the microbial ecology of cultivated land must be considered.

Serine Supplementation in the Diets of Late Gestating and Lactating Sows Improves Selenium Nutritional Status in Sows and Their Offspring.

Serine can regulate selenoprotein expression, and dietary serine is correlated with the contents of plasma selenoprotein P (Sepp1) and milk selenium (Se) in lactating mothers. Based on this, we investigated the effects of serine supplementation in the diets of late gestating and lactating sows on Sepp1 and Se contents in sows and their offspring. A total of 72 sows were assigned to four groups. During the experiment, sows were fed either a basal diet or basal diets supplemented with three different levels of serine. The results showed that maternal dietary serine had no effect on the Se content in the serum of sows and their offspring, whereas it significantly increased the Se content in the liver of piglets at the age of 21 days. Maternal dietary serine significantly increased Sepp1 content, either in the serum of sows or that in their offspring at the ages of 3 days, 7 days, and 21 days. Additionally, maternal dietary serine significantly increased litter weight and the average body weight of piglets at the age of 11 days. Notably, a positive correlation was found between the average body weight of piglets at the age of 11 days and serum Sepp1 content in piglets, at the age of either 3 days or 7 days. In conclusion, maternal dietary serine supplementation could improve Se nutritional status in sows and their offspring. These beneficial changes may contribute to the higher body weight of the offspring.

Exogenous and Endogenous Serine Deficiency Exacerbates Hepatic Lipid Accumulation.

Serine is involved in the regulation of hepatic lipid metabolism. However, whether exogenous or endogenous serine deficiency affects lipid accumulation in the liver and related mechanisms is unclear. Here, we investigated the effects of serine deficiency on hepatic fat accumulation in mice fed a serine-deficient diet or in mice supplemented with the D-3-phosphoglycerate dehydrogenase (PHGDH) inhibitor NCT-503. Both treatments produced an increase in body weight and liver weight and higher triglyceride content in the liver. Both treatments also exacerbated hepatic inflammatory responses and oxidative stress. Importantly, NCT-503 supplementation significantly inhibited PHGDH activity and decreased the serine content in the liver. Dietary serine deficiency significantly affected the colonic microbiota, characterized by a decreased ratio of Firmicutes/Bacteroidetes and decreased proportion of Bifidobacterium. Dietary serine deficiency additionally resulted in significantly decreased colonic and serum acetate and butyrate levels. The collective results indicate that NCT-503 supplementation may contribute to overaccumulation of hepatic lipid, by causing hepatic serine deficiency, while dietary serine deficiency may produce similar outcomes by affecting the gut-microbiota-liver axis.

Pollution by Antibiotics and Antimicrobial Resistance in LiveStock and Poultry Manure in China, and Countermeasures.

The demand for animal protein has increased considerably worldwide, especially in China, where large numbers of livestock and poultry are produced. Antibiotics have been widely applied to promote growth and prevent diseases. However, the overuse of antibiotics in animal feed has caused serious environmental and health risks, especially the wide spread of antimicrobial resistance (AMR), which seriously affects animal and human health, food safety, ecosystems, and the sustainable future development of animal protein production. Unfortunately, AMR has already become a worldwide challenge, so international cooperation is becoming more important for combatting it. China's efforts and determination to restrict antibiotic usage through law enforcement and effective management are of significance. In this review, we address the pollution problems of antibiotics; in particular, the AMR in water, soil, and plants caused by livestock and poultry manure in China. The negative impact of widespread and intensive use of antibiotics in livestock production is discussed. To reduce and mitigate AMR problems, we emphasize in this review the development of antibiotic substitutes for the era of antibiotic prohibition.

The Associated Regulatory Mechanisms of Zinc Lactate in Redox Balance and Mitochondrial Function of Intestinal Porcine Epithelial Cells.

Zinc lactate (ZnLA) is a new organic zinc salt which has antioxidant properties in mammals and can improve intestinal function. This study explored the effects of ZnLA and ZnSO4 on cell proliferation, Zn transport, antioxidant capacity, mitochondrial function, and their underlying molecular mechanisms in intestinal porcine epithelial cells (IPEC-J2). The results showed that addition of ZnLA promoted cell proliferation, inhibited cell apoptosis and IL-6 secretion, and upregulated the mRNA expression and concentration of MT-2B, ZNT-1, and CRIP, as well as affected the gene expression and activity of oxidation or antioxidant enzymes (e.g., CuZnSOD, CAT, and Gpx1, GSH-PX, LDH, and MDA), compared to ZnSO4 or control. Compared with the control, ZnLA treatment had no significant effect on mitochondrial membrane potential, whereas it markedly increased the mitochondrial basal OCR, nonmitochondrial respiratory capacity, and mitochondrial proton leakage and reduced spare respiratory capacity and mitochondrial reactive oxygen (ROS) production in IPEC-J2 cells. Furthermore, ZnLA treatment increased the protein expression of Nrf2 and phosphorylated AMPK, but reduced Keap1 and p62 protein expression and autophagy-related genes LC3B-1 and Beclin mRNA abundance. Under H2O2-induced oxidative stress conditions, ZnLA supplementation markedly reduced cell apoptosis and mitochondrial ROS levels in IPEC-J2 cells. Moreover, ZnLA administration increased the protein expression of Nrf2 and decreased the protein expression of caspase-3, Keap1, and p62 in H2O2-induced IPEC-J2 cells. In addition, when the activity of AMPK was inhibited by Compound C, ZnLA supplementation did not increase the protein expression of nuclear Nrf2, but when Compound C was removed, the activities of AMPK and Nfr2 were both increased by ZnLA treatment. Our results indicated that ZnLA could improve the antioxidant capacity and mitochondrial function in IPEC-J2 cells by activating the AMPK-Nrf2-p62 pathway under normal or oxidative stress conditions. Our novel finding also suggested that ZnLA, as a new feed additive for piglets, has the potential to be an alternative for ZnSO4.

Ulva prolifera Extract Alleviates Intestinal Oxidative Stress via Nrf2 Signaling in Weaned Piglets Challenged With Hydrogen Peroxide.

Background: Ulva prolifera extract contains a variety of functional active substances. Whether these substances had any beneficial effects on the small intestine of weaned piglets under oxidative stress remained unknown. Method: We explored the effects of U. prolifera extract on oxidative stress and related mechanisms in weaned piglets and intestinal porcine epithelial cells (IPEC-J2) challenged with hydrogen peroxide. Results: U. prolifera extract was found to mainly consist of polyphenols and unsaturated fatty acids. U. prolifera extract increased total antioxidant capacity and superoxide dismutase (SOD) activity, while it decreased malondialdehyde content, in the serum of weaned piglets challenged with hydrogen peroxide. Moreover, U. prolifera extract increased mRNA expression of SOD and catalase, as well as the intestinal expression of nuclear NF-E2-related factor 2 (Nrf2), both in vitro and in vivo. Furthermore, U. prolifera extract decreased reactive oxygen species and improved mitochondrial respiration in IPEC-J2 cells treated with hydrogen peroxide. However, AMPK inhibition did not affect nuclear Nrf2 expression and only partially affected the effects of U. prolifera extract on oxidative stress. Conclusion: We suggest that U. prolifera extract alleviates oxidative stress via Nrf2 signaling, but independent of AMPK pathway in weaned piglets challenged with hydrogen peroxide. These results shed new insight into the potential applications of U. prolifera extract as a therapeutic agent for the prevention and treatment of oxidative stress-induced intestinal diseases.

Glutamate and aspartate alleviate testicular/epididymal oxidative stress by supporting antioxidant enzymes and immune defense systems in boars.

Several potential oxidative agents have damaging effects on mammalian reproductive systems. This study was conducted to investigate the effects of glutamate (Glu) and aspartate (Asp) supplementation on antioxidant enzymes and immune defense systems in the outer scrotum of boars injected with H2O2. A total of 24 healthy boars were randomly divided into 4 treatment groups: control (basal diet, saline-treated), H2O2 (basal diet, H2O2-challenged outer scrotum (1 mL kg-1 BW)), Glu (basal diet +2% Glu, H2O2-challenged), and Asp (basal diet+2% Asp, H2O2-challenged). Our results showed that both Glu and Asp supplementation improved testicular morphology and decreased the genital index in the H2O2-treated boars. Glu and Asp administration increased the antioxidant enzyme activities and affected the testicular inflammatory cytokine secretion but had no effect on sex hormone levels. Furthermore, the mRNA expression of CAT, CuZnSOD, and GPx4 was altered in the testes and epididymis of boars treated with Asp and Glu. Glu and Asp supplementation also modulated the expression of TGF-ß1, IL-10, TNF-α, IL-6 and IL-1ß in the testis and epididymis. These results indicate that dietary Glu and Asp supplementation might enhance antioxidant capacity and regulate the secretion and expression of inflammatory cytokines to protect the testes and epididymis of boars against oxidative stress.

Transcriptome profiling of the liver among the prenatal and postnatal stages in chickens.

The liver is an important organ that has pivotal functions in the synthesis of several vital proteins, the metabolism of various biologically useful materials, the detoxification of toxic substances, and immune defense. Most liver functions are not mature at a young age and many changes happen during postnatal liver development, which lead to differential functions of the liver at different developmental stages. However, the transcriptome details of what changes occur in the liver after birth and the molecular mechanisms for the regulation of the developmental process are not clearly known in chickens. Here, we used RNA-sequencing to analyze the transcriptome of chicken liver from the prenatal (at an embryonic day of 13) to the postnatal stages (at 5 wk and 42 wk of age). A total of approximately 161.17 Gb of raw data were obtained, with 4,127 putative and 539 differentially expressed lncRNAs, and with 13,949 putative and 6,370 differentially expressed mRNAs. Coexpression of lncRNAs-mRNAs in hepatic transcriptome analysis showed that the liver plays important roles in providing energy for organisms through the mitochondrial respiratory chain in chickens, meanwhile, acting as a crucial part of antioxidant stress. The developmental transcriptome date revealed that antioxidant defenses are likely to act on chicken embryo development and that significant functional changes during postnatal liver development are associated with the liver maturation of chickens. These results provide a timeline for the functional transcriptome transition from the prenatal to adult stages in chickens and will be helpful to reveal the underlying molecular mechanisms of liver development.

Targeting peptide-enhanced antibody and CD11c+ dendritic cells to inclusion bodies expressing protective antigen against ETEC in mice.

Enterotoxigenic Escherichia coli (ETEC) remains a massive burden in developing countries with increasing morbidity and mortality rates; it is also an important pathogen in the farming industry and is a leading cause of bacterial diarrhea. Our previous study showed that nanometer-sized inclusion bodies (IBs) of the fimbrial adhesin subunit protein (FaeG), mutation heat-stable enterotoxin a (mSTa), heat-labile enterotoxin b (LTb), and STb (nontargeting) fusion protein as an oral vaccine induced both systemic and mucosal immune responses. In this study, to enhance the protective efficacy to ETEC, we used Yersinia enterocolitica adhesive and M-cell-targeting peptides to analyze high-efficiency antigen-specific immune presentation in the gut. Here, we showed that immunization with the IBs of ETEC-FaeG-mSTa-LTb-STb-induced a specific systemic and mucosal immune response in the gut, whereas the combination of both targeting peptides resulted in the highest titer, protective immune response against ETEC. A lymphocyte proliferation assay has shown that the IBs induced immunologic memory. The specific antibody of the targeting groups could effectively neutralize toxins, thereby protecting the cells of the small intestine and reducing the level of cAMP and cGMP, and the groups with double targeting showed the best effect. The most important finding was that the targeting peptides stimulate the T helper (Th) cells through Th17 and Th1 and that Th1 cells dominated the cellular immune response. We found that the targeting peptide could also activate CD11c+ on lymphoid dendritic cells, which processed and presented antigens to T cells through Th1-mediated IFN-γ and IL-12, thereby enhancing the antibody titers. The double-targeting peptide had a better effect on stimulating the immune cells to enhance the antibody titers.-Jiang, X., Xia, S., He, X., Ma, H., Feng, Y., Liu, Z., Wang, W., Tian, M., Chen, H., Peng, F., Wang, L., Zhao, P., Ge, J., Liu, D. Targeting peptide-enhanced antibody and CD11c+ dendritic cells to inclusion bodies expressing protective antigen against ETEC in mice.

Phosphatidylcholine could protect the defect of zearalenone exposure on follicular development and oocyte maturation.

Zearalenone (ZEA) is a well-known exogenous endocrine disruptor and can lead to severe negative effects on the human and animal reproductive process. Using a follicle culture model, we have previously shown that ZEA exposure significantly affected the follicular development and antrum formation but the underlying mechanisms are not well known. Therefore, in this study, we explored the metabolomic changes of granulosa cell (GC) culture media with or without ZEA exposure. The results showed that ZEA significantly increased phosphatidylcholine or phosphatidyl ethanolamine adducts in culture medium. A comprehensive analysis with the metabolome data from follicular fluid of small and large antral follicles showed that lyso phosphatidylcholine (LPC) was accumulated during follicle growth, but was depleted by ZEA exposure. Exogenous supplement with LPC to the follicle growth media or oocyte maturation media can partly protect the defect of ZEA exposure on follicular antrum formation and oocyte maturation. Taken together, our results demonstrate that ZEA exposure hinders the follicular growth and exogenous LPC can practically protect the defect of ZEA on follicular development and oocyte maturation.

Exposure to Zinc oxide nanoparticles during pregnancy induces oocyte DNA damage and affects ovarian reserve of mouse offspring.

Zinc oxide nanoparticles (nZnO) have been shown to have higher toxic effects likely due to their ion-shedding ability and low solubility under neutral conditions. In order to investigate whether exposure to nZnO during embryonic development affects ovary development, 12.5 day post coitum (dpc) fetal mouse ovaries were cultured in the presence of nZnO for 6 days. We found that the nanoparticles (NPs) accumulated within the oocyte cytoplasm in a dose dependent manner, caused DNA damage and apoptosis, and result in a significant decrease in oocyte numbers. No such effects were observed when the ovaries were incubated in the presence of ZnSO4 or bulk ZnO as controls. In addition, we injected intravenously 16 mg/kg body weight nZnO in 12.5 dpc pregnant mice on two consecutive days and analyzed the ovaries of fetuses or offspring at three critical periods of oogenesis: 17.5 dpc, 3 days post-partum (dpp) and 21 dpp. Evidence of increased DNA damage in pachytene oocytes in fetal ovaries and impaired primordial follicle assembly and folliculogenesis dynamics in the ovaries of the offspring were found. Our results indicate that certain types of NPs affect pre- and post-natal oogenesis in vitro and in vivo.