Global warming induced heat stress severely impairs porcine oocyte quality due to their high lipid content, disrupting reproductive performance. This study combined transcriptomic and metabolomic analyses of heat-stressed porcine oocytes, identifying glutathione metabolism, arginine and proline metabolism, and purine biosynthesis as key perturbed pathways. We focused on arginine due to the significant depletion of arginine and its downstream metabolites in heat stressed oocytes. Exogenous arginine supplementation was applied to heat-stressed immature oocytes. Results showed arginine protects polar body extrusion, normalized spindle/chromosome configuration, and maintained actin cytoskeleton and endoplasmic reticulum (ER) integrity. It also repaired mitochondrial structural and functional impairments, elevated membrane potential, reduced reactive oxygen species accumulation, and alleviated DNA damage and apoptosis. These findings confirm arginine decreases heat stress induced porcine oocyte deterioration by preserving cellular structure, improving mitochondrial function and relieving oxidative stress related damage, highlighting its potential as a targeted nutritional supplement to preserve porcine oocyte quality and improve their developmental potential under heat stress conditions.
Sodium dehydroacetate (Na-DHA), a widely used antimicrobial food additive, raises bioaccumulation and organ toxicity concerns, with female reproductive effects remaining understudied. This study investigates Na-DHA's impact on porcine oocyte maturation and evaluates nicotinamide mononucleotide (NMN) as a protective agent. Na-DHA exposure impaired oocyte maturation, suppressing first polar body extrusion and cumulus expansion. Metabolomic analysis revealed disrupted energy metabolism via tricarboxylic acid (TCA) cycle inhibition, notably reducing succinate and fumarate levels. Molecular docking confirmed Na-DHA competitively binds α-ketoglutarate dehydrogenase (α-KGDH), a key TCA enzyme, impairing mitochondrial ATP synthesis and elevating oxidative stress. These metabolic defects induced cytoskeletal abnormalities (spindle disorganization, actin disruption, cortical granule mislocalization), reducing fertilization rates and compromising blastocyst development. NMN supplementation restored mitochondrial function, mitigated oxidative stress and apoptosis, and rescued meiotic progression, enhancing embryonic outcomes. The findings elucidate Na-DHA's reproductive toxicity via α-KGDH-mediated TCA cycle suppression and mitochondrial dysfunction, while demonstrating NMN's protective role through NAD+-dependent metabolic homeostasis. This study highlights Na-DHA's risks to oocyte quality and proposes NMN as a potential therapeutic strategy to counteract food additive-induced reproductive damage.
Butyl benzyl phthalate (BBP), a widely used plasticizer and solvent, has raised concerns due to its pervasive presence in the environment and human bodies, prompting worries about its potential health risks. This study aims to uncover the impact of BBP on pre-implantation embryo development and its underlying mechanisms. The experimental results indicate that BBP exposure significantly inhibits the development process of early embryos, reducing the proportion of embryos reaching key formation stages. Through transcriptomic and metabolomic analyses, we found that BBP exposure leads to marked changes in gene expression and metabolite levels associated with mitochondrial function and protein translation, accompanied by structural damage to the endoplasmic reticulum and Golgi apparatus. The study also reveals that BBP may disrupt mitochondrial function through interaction with the mitochondrial membrane protein NDUFA11, thereby inducing oxidative stress and apoptosis. The innovation of this research lies in proposing that silibinin, a natural antioxidant, can effectively alleviate BBP-induced developmental disorders in embryos, offering a new strategy for protecting maternal reproductive health. This work not only provides a scientific basis for understanding the embryotoxicity of BBP but also offers important insights for the health risk assessment and prevention of environmental endocrine disruptors.
Oocyte quality is closely linked to metabolic integrity, and age-related metabolic dysregulation is a key factor contributing to oocyte aging. In this study, we utilized non-targeted metabolomics to explore the impact of taurine supplementation on the metabolic profile of postovulatory aging (POA) porcine oocytes. Our analysis revealed that taurine supplementation significantly altered the metabolic landscape, restoring key metabolic pathways associated with energy production, amino acid metabolism, and oxidative stress regulation. Notably, taurine supplementation enhanced mitochondrial function, increased ATP synthesis, and improved the redox balance by upregulating reduced glutathione (GSH) levels and reducing oxidative damage. Metabolomics data also indicated a restoration of critical metabolic intermediates, including those involved in the glutathione synthesis pathway and amino acid metabolism. These findings suggest that taurine can modulate oocyte metabolism, improve cellular energy status, and mitigate oxidative stress, thereby enhancing oocyte quality at the metabolic level.
Perfluorooctanesulfonate (PFOS) is a persistent environmental endocrine disruptor that poses severe threats to mammalian reproductive health upon accumulation in organisms. Therefore, elucidating the mechanisms of PFOS-induced damage and identifying effective protective strategies are of critical importance. In this study, an untargeted metabolomic analysis revealed that PFOS exposure significantly disrupted metabolic homeostasis in oocytes. Using public databases to predict potential target proteins of PFOS and performing KEGG pathway enrichment analysis, we identified the tryptophan metabolism pathway as a key target of PFOS. Molecular docking and molecular dynamics simulations demonstrated specific binding between PFOS and proteins involved in the tryptophan metabolism pathway, leading to dynamic structural alterations in these proteins. Furthermore, supplementation with tryptophan was shown to significantly enhance mitochondrial function in oocytes, regulate the glutathione (GSH)/oxidized glutathione (GSSG) ratio, reduce reactive oxygen species (ROS) levels, and alleviate oxidative stress, thereby mitigating the decline in oocyte quality caused by PFOS exposure. These findings provide novel theoretical insights and research directions for using tryptophan as a protective agent against PFOS-induced reproductive toxicity.
The immune system acts as a vital defense barrier against pathogenic invasions, and its stable operation is crucial for maintaining body health. Nevertheless, various natural or artificial factors can compromise the body's immune function, leading to immunosuppression, which may interfere with the efficacy of vaccination and increase the susceptibility of the body to disease-causing pathogens. In an effort to ensure successful vaccinations and improve overall physical well-being, the search for appropriate immune regulators to enhance immunity is of paramount importance. Lentinan (LNT) has a significant role in immune regulation and vaccine adjuvants. In the present study, we constructed an immunosuppressive model using dexamethasone (DEX) and demonstrated that LNT could significantly improved antibody levels in immunosuppressive mice and stimulated T-lymphocyte proliferation and differentiation in intestinal Peyer's patches. LNT also increased the production of secretory immunoglobulin A (sIgA) in the duodenal fluid, the number of goblet cells, and the proportion of mucin area. Moreover, LNT modulated the intestinal microbiota and increased the production of short-chain fatty acids. Additionally, LNT promoted the proliferation, differentiation, and pro-inflammatory cytokines production of DEX-treated splenic T lymphocytes in vitro. Thus, the present study highlights the potential of LNT in reversing immunosuppression and avoiding the failure of vaccination.
Butyl benzyl phthalate (BBP) is a common environmental pollutant, it is high in paints, adhesives and other decorative materials, food packaging bags, cleaning agents, is a plasticizer is very widely used in daily life. However, it remains unknown whether BBP causes damage to oocytes cultured in vitro and whether there is an effective rescue strategy. Here, we evaluated the effects of exposure to different concentrations of BBP (10, 50, and 100 μM) on the meiosis of porcine oocytes. The results showed that exposure to BBP (100 μM) severely impaired expansion of cumulus-oocyte complex (COCs) and PBE (control:71.6% vs 100 μM: 48.8%). Spindle conformation and chromosome alignment were also significantly abnormal (34.8% and 46.0%, respectively) compared to the control (11.1% and 17.5%, respectively), and BBP caused damage to microfilaments and cortical granules (CGs). In addition, oocyte exposure to BBP induced impaired mitochondrial function and disrupted mitochondrial integrity. Silibinin is a natural active substance isolated from the seeds of Silybum marianum (L.) Gaertneri with strong antioxidant and anti-inflammatory effects. Noteworthy, we added different concentrations of silibinin (10, 20, and 50 μM) to BBP-exposed oocytes for rescue experiments, where 50 μM effectively rescued BBP-induced meiotic failure (70.6%). It also prevented the generation of excessive autophagy and apoptosis in oocytes by inhibiting the production of ROS. In a word, our results suggest that supplementation of silibinin attenuates the impaired oocyte development caused by BBP exposure,which provides a potential strategy to protect oocytes from environmental pollutants.
Advanced age is a primary risk factor for female infertility due to reduced ovarian reserve and declining oocyte quality. However, as an important contributing factor, the role of metabolic regulation during reproductive aging is poorly understood. Here, we applied untargeted metabolomics to identify spermidine as a critical metabolite in ovaries to protect oocytes against aging. In particular, we found that the spermidine level was reduced in ovaries of aged mice and that supplementation with spermidine promoted follicle development, oocyte maturation, early embryonic development and female fertility of aged mice. By microtranscriptomic analysis, we further discovered that spermidine-induced recovery of oocyte quality was mediated by enhancement of mitophagy activity and mitochondrial function in aged mice, and this mechanism of action was conserved in porcine oocytes under oxidative stress. Altogether, our findings suggest that spermidine supplementation could represent a therapeutic strategy to ameliorate oocyte quality and reproductive outcome in cis-gender women and other persons trying to conceive at an advanced age. Future work is needed to test whether this approach can be safely and effectively translated to humans. Advanced age is a primary risk factor for female infertility due to declining oocyte quantity and quality. Here Yu Zhang et al. report that supplementation with spermidine rejuvenates the quality of oocytes from aged mice at least in part by enhancing mitophagy and mitochondrial function.
Mouse germinal vesicle (GV) oocytes are divided into surrounded nucleolus (SN) and nonsurrounded nucleolus (NSN) oocytes based on chromatin morphology. NSN oocytes spontaneously transform into SN oocytes after accumulating enough maternal transcripts. SN oocytes show transcriptional silencing. When oocyte maturation is abnormal or takes place in vitro, NSN oocytes do not go through SN stage before proceeding to MII. Nontransitive oocytes show developmental retardation, a low fertilization rate, and arrest at the two-cell embryo stage in mice. Here, chromatin-binding ribonucleic acid polymerase II (RNAP II) activity, newly synthesized RNA, and chromatin accessibility in GV oocytes were examined. In SN oocytes, RNAP II did not bind to DNA, neo-RNA was not generated in nuclei, and the phosphorylation state of RNAP II did not affect the chromatin-binding activity. The number of accessible genes in SN oocytes was remarkably lower than that in NSN oocytes. The accessibility of different functional genes was also different between the two types of oocytes. Thus, low chromatin accessibility leads to transcriptional silencing in SN oocytes.
Diisononyl phthalate (DINP), a mixture of chemical compounds composed of diverse isononyl esters of phthalic acid, is commonly applied as a plasticizer to substitute for di (2-ethylhexyl) phthalate (DEHP). It has been demonstrated that DINP exposure impairs the functions of kidney and liver in animals. However, the effects and potential mechanisms of DINP exposure on the female reproduction, especially the oocyte quality are still poorly understood. Here, we discovered that DINP exposure weakened the porcine oocyte meiotic competency (78.9% vs 53.6%, P < 0.001) and fertilization ability (78.5% vs 34.1%, P < 0.0001) during in vitro maturation. Specifically, DINP exposure induced the persistent spindle assembly checkpoint (SAC) activation caused by the disorganized spindle/chromosome apparatus (spindle: 20.0% vs 83.3%, P < 0.001; chromosome: 20.0% vs 80.0%, P < 0.01) to arrest meiotic progression of oocytes at metaphase I stage. In addition, DINP exposure disturbed the dynamics of sperm binding (146.7 vs 58.6, P < 0.0001) and fusion proteins (19.5 vs 11.6, P < 0.0001) in oocytes to compromise their fertilization ability. In particular, transcriptome data uncovered that the action mechanism of DINP on the oocyte maturation was associated with oxidative phosphorylation, apoptosis and autophagy pathways. Lastly, we validated that DINP exposure resulted in the mitochondrial dysfunction (27.2 vs 19.8, P < 0.0001) and elevated levels of reactive oxygen species (ROS; 8.9 vs 19.9, P < 0.0001) to trigger the occurrence of apoptosis (7.2 vs 13.1, P < 0.0001) and protective autophagy (68.6 vs 139.3, P < 0.01). Altogether, our findings not only testify that DINP has a potentially adverse impact on the mammalian oocyte quality, but also provide a scientific reference regarding how environment pollutants act on the female germ cell development.
Previous studies have demonstrated that lipopolysaccharide (LPS), as a central toxic factor of gram-negative bacteria, can induce oxidative stress and cellular inflammation to result in the impairment of female fertility in different organisms. Particularly, it has harmful effects on the oocyte quality and subsequent embryonic development. However, the approach concerning how to prevent oocytes from LPS-induced deterioration still remains largely unexplored. We assessed the effective influences of velvet antler water extract (VAWE) by immunostaining and fluorescence intensity quantification on the meiotic maturation, mitochondrial function and sperm binding ability of oocytes under oxidative stress. Here, we report that VAWE treatment restores the quality of porcine oocytes exposed to LPS. Specifically, LPS exposure contributed to the failed oocyte maturation, reduced sperm binding ability and fertilization capability by disturbing the dynamics and arrangement of meiotic apparatuses and organelles, including spindle assembly, chromosome alignment, actin polymerization, mitochondrial dynamics and cortical granule distribution, the indicators of oocyte nuclear and cytoplasmic maturation. Notably, VAWE treatment recovered these meiotic defects by removing the LPS-induced excessive ROS and thus inhibiting the apoptosis. Collectively, our study illustrates that VAWE treatment is a feasible strategy to improve the oocyte quality deteriorated by the LPS-induced oxidative stress.
Dear Editor, Postovulatory aging would occur to impair the oocyte quality in a time-dependent manner if ovulated oocytes are not fertilized within the optimal tim-ing in the oviduct or in the dishes(Trapphoff et al.,2016),which might re-sult in the early pregnancy failure in vivo and adverse outcome of assisted repro-ductive technology(ART)in vitro(Nagy et al.,1993;Wilcox et al.,1998).How-ever,the effective approaches to pre-venting the postovulatory aging-induced oocyte deterioration are still underex-plored.
Background: Elevated ambient temperature-caused heat stress is a major concern for livestock production due to its negative impact on animal feed intake, growth, reproduction, and health. Particularly, the germ cells are extremely sensitive to the heat stress. However, the effective approach and strategy regarding how to protect mammalian oocytes from heat stress-induced defects have not been determined.Methods: Germinal vesicle(GV) porcine oocytes were cultured at 41.5 ℃ for 24 h to induce heat stress, and then cultured at 38.5 ℃ to the specific developmental stage for subsequent analysis. Nicotinamide mononucleotide(NMN) was dissolved in water to 1 mol/L for a stock solution and further diluted with the maturation medium to the final concentrations of 10 μmol/L, 20 μmol/L, 50 μmol/L or 100 μmol/L, respectively, during heat stress.Immunostaining and fluorescence intensity quantification were applied to assess the effects of heat stress and NMN supplementation on the key processes during the oocyte meiotic maturation.Results: Here, we report that NMN supplementation improves the quality of porcine oocytes under heat stress.Specifically, we found that heat stress resulted in oocyte maturation failure by disturbing the dynamics of meiotic organelles, including the cytoskeleton assembly, cortical granule distribution and mitochondrial function. In addition, heat stress induced the production of excessive reactive oxygen species(ROS) and DNA damage, leading to the occurrence of apoptosis in oocytes and subsequent embryonic development arrest. More importantly, we validated that supplementation of NMN during heat stress restored the meiotic defects during porcine oocyte maturation.Conclusions: Taken together, our study documents that NMN supplementation is an effective approach to improve the quality of oocytes under heat stress by promoting both nuclear and cytoplasmic maturation.
The low quality of oocytes is one of the main causes of the suboptimal reproductive outcome of female mammals with advanced maternal age. Here, we present a detailed protocol to obtain high-quality oocytes and embryos from aged mice by nicotinamide mononucleotide (NMN) administration. We also describe fluorescence staining procedures to assess the organelle dynamics in oocytes, and in vitro fertilization and embryo culture systems to evaluate the influence of NMN on the fertilization ability and embryonic development potential. For complete information on the use and execution of this protocol, please refer to Miao et al. (2020).
<span id="ChDivSummary" name="ChDivSummary" class="abstract-text">目的了解南京市大学生健康素养水平和生命质量的现状,探讨大学生健康素养水平与生命质量之间的关系。方法采用分层整群随机抽样方法,利用健康素养问卷、EQ-5D量表对南京市部分高校大学生进行面对面的问卷调查,应用SPSS软件对数据进行统计描述、单因素和多因素统计分析。结果南京市大学生健康素养水平为38.1%。健康知识、健康生活方式与行为、健康技能具备率分别为65.2%、42.6%、46.9%。南京市大学生生命质量:EQ-5D均分为(0.92±0.11)分,自评均分为(85.13±12.49)分。单因素分析显示,女生、高年级、医科生、母亲文化程度高的大学生具有更高的健康素养水平(P <0.05);男生、低年级、文理科学生具有更高的生命质量(P <0.05)。多因素分析显示,学科(OR=2.316,95%CI=1.837~2.920)、年级(OR=1.138,95%CI=1.019~1.271)、学校(OR=1.253,95%CI=1.109~1.415)、母亲文化程度(OR=1.124,95%CI=1.069~1.183)、学习状况(OR=0.898,95%CI=0.849~0.950)以及月消费(OR=0.947,95%CI=0.902~0.995)对大学生健康素养均有影响。大学生健康素养得分与健康相关生命质量相关系数为0.042(医学生和非医学生分别为0.040和0.046)。结论南京市大学生健康素养水平较高,但是其健康素养得分与健康相关生命质量存在极弱的正相关。</span>
Advanced maternal age is highly associated with a decline in oocyte quality, but effective approaches to improve it have still not been fully determined. Here, we report that in vivo supplementation of nicotinamide mononucleotide (NMN) efficaciously improves the quality of oocytes from naturally aged mice by recovering nicotinamide adenine dinucleotide (NAD(+)) levels. NMN supplementation not only increases ovulation of aged oocytes but also enhances their meiotic competency and fertilization ability by maintaining the normal spindle/chromosome structure and the dynamics of the cortical granule component ovastacin. Moreover, single-cell transcriptome analysis shows that the beneficial effect of NMN on aged oocytes is mediated by restoration of mitochondrial function, eliminating the accumulated ROS to suppress apoptosis. Collectively, our data reveal that NMN supplementation is a feasible approach to protect oocytes from advanced maternal age-related deterioration, contributing to the improvement of reproductive outcome of aged women and assisted reproductive technology.
研究型教学模式是我国高等教育教学改革发展方向,对培养创新型高素质人才具有非常重要的意义,本文介绍了在劳动与社会保障专业基础课中开展研究型教学模式的具体实践,为本科教育开展研究型教学模式并提高教学效果与质量提供思路.
Objective To assess the effect of health education on tuberculosis control among community residents in Jiangsu province and to provide basis for planning health education program. Methods Cross-sectional studies with stratified cluster sampling were carried out before and after a health education among community residents aged 20-69 years in Zhangjiagang,Taixing,and Danyang city. With the questionnaire surveys,information about aw areness of and attitude tow ards tuberculosis prevention and treatement were collected. Non-conditional multiple-factor logistic regression was adopted in data analyses. Results There were 19 106 people in the baseline survey and 11 384 people in the terminal survey. After the health education,the total aw areness rate for 8 key iterms of tuberculosis prevention and treatment was increased from 60. 4% to 67. 5% and the qualification rate for tuberculosis know ledge increased from 46. 4% to 52. 8%. At the same time,the proportion of residents with right attitude to tuberculosis patient increased from 68. 0% to 78. 9%. The results of non-conditional multiple-factor logistic regression indicated that the differences in the rate and proportion were statistically significant(P < 0. 05 for all). Conclusion The community residents' know ledge level for tuberculosis prevention and treatment is low and the level can be increased by health education but efforts should be made to meet the requirement of national tuberculosis prevention plan.
OBJECTIVE To analyze association between psycho-social factors and AIDS preventive behaviors among 1 447 migrant population. METHODS Questionnaire designed based on Health Belief Model, applied convenience sampling survey to collect information in Zhangjiagang and Danyang, multiple regression was used in statistical analysis. RESULTS Adjusted Health Belief Model showed that the AIDS preventive behavior among migrant population had significant association with perceived benefits (py11=10.51, P=0.000) and perceived barriers (py12=-2.59, P=0.010), while had no association with perceived susceptibility and perceived severity of the disease. Social and cultural factors , like gender, marriage status, living condition and social action had direct influences on the preventive behaviors while AIDS knowledge had indirect influences through four health beliefs. CONCLUSION The roles of various factors in Health Belief Model are different; health education strategy should be targeted to characteristics of migrant population.
Objective To evaluate the effect of health education on treatment compliance in patients with hepatitis B and provide basis for outlining strategy on health education intervention of hepatitis B.Methods A computerized literature search was carried out in CNKI(Chinese National Knowledge Infrastructure),Wanfang,PubMed,Elsevier and Embase databases to collect articles published between 2000 and 2010 concerning the effect of health education intervention on patients with hepatitis B.The study type of archives was self-control intervention study and software RevMan4.2 was used.Meta-analysis was performed to assess 8 outcomes of the intervention on treatment compliance.Fixed and random effect models were employed to combine results after a heterogeneity test,with rate difference(RD) used as the indicator of intervention effect.Results The analysis showed that the RD for each indicator was increased obviously.Among them,the common side-effect of follow-up and traditional diet were increased most significantly by 77% and 66%.Conclusion Health education intervention on patients with hepatitis B can take effect on raising treatment compliance,reducing the relapse rate,enhancing protective capability and improving the quality of life.