Acute exposure of triclocarban affects early embryo development in mouse through disrupting maternal-to-zygotic transition and epigenetic modifications.

Triclocarban (TCC) is a broad-spectrum antibacterial agent used globally, and high concentrations of this harmful chemical exist in the environment. The human body is directly exposed to TCC through skin contact. Moreover, TCC is also absorbed through diet and inhaled through breathing, which results in its accumulation in the body. The safety profile of TCC and its potential impact on human health are still not completely clear; therefore, it becomes imperative to evaluate the reproductive toxicity of TCC. Here, we explored the effect of TCC on the early embryonic development of mice and its associated mechanisms. We found that acute exposure of TCC affected the early embryonic development of mice in a dose-dependent manner. Approximately 7600 differentially expressed genes (DEGs) were obtained by sequencing the transcriptome of 2-cell mouse embryos; of these, 3157 genes were upregulated and 4443 genes were downregulated in the TCC-treated embryos. GO and KEGG analysis revealed that the enriched genes were mainly involved in redox processes, RNA synthesis, DNA damage, apoptosis, mitochondria, endoplasmic reticulum, Golgi apparatus, cytoskeleton, peroxisome, RNA polymerase, and other components or processes. Moreover, the Venn analysis showed that the zygotic genome activation (ZGA) was affected and the degradation of maternal effector genes was inhibited. TCC induced changes in the epigenetic modification of 2-cell embryos. The level of DNA methylation increased significantly. Further, the levels of H3K27ac, H3K9ac, and H3K27me3 histone modifications decreased significantly, whereas those of H3K4me3 and H3K9me3 modifications increased significantly. Additionally, TCC induced oxidative stress and DNA damage in the 2-cell embryos. In conclusion, acute exposure of TCC affected early embryo development, destroyed early embryo gene expression, interfered with ZGA and maternal gene degradation, induced changes in epigenetic modification of early embryos, and led to oxidative stress and DNA damage in mouse early embryos.

Curcumin alleviates bisphenol AF-induced oxidative stress and apoptosis in caprine endometrial epithelial cells via the Nrf2 signaling pathway.

Bisphenol AF (BPAF), a BPA-substitute, has been widely used in industrial compounds throughout the world. Several studies have shown that BPAF has endocrine interference and reproductive toxicity. However, the toxic effects of BPAF on pregnancy and placenta of goats are still unclear. Therefore, the objective of this study was to reveal the toxic effect of BPAF by using an in vitro culture model of caprine endometrial epithelial cells (EECs) and further attempted to alleviate the toxicity by curcumin pretreatment. The results showed that BPAF induces significant effects on EECs, including decreased cell viability and mitochondrial membrane potential (△ψm), elevating intracellular reactive oxygen species (ROS), promoting cell apoptosis through upregulating the expression of Bax, Cytochrome c, and downregulating the expression of Bcl-2. Meanwhile, BPAF induced dysregulation of oxidative stress by increasing the levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) but decreasing the activities of superoxide dismutase (SOD). However, curcumin pretreatment could significantly attenuate BPAF-induced toxic effects in EECs. Further study revealed that BPAF treatment could activate mitogen-activated protein kinase (MAPK) pathway and nuclear factor-erythroid 2-related factor 2 (Nrf2) expression, but curcumin pretreatment significantly inhibited the activation of MAPK signal pathway and Nrf2 expression induced by BPAF. Overall, this study indicated that curcumin could prevent BPAF-induced EECs cytotoxicity, which provides a potential therapeutic strategy for female infertility associated with BPAF exposure.

Comparison of intravenous and oral administration of acetaminophen in adults undergoing general anesthesia.

BACKGROUND: Acetaminophen is a widely clinically used analgesic. However, the clinical effect of the route of administration on postoperative analgesia as well as on postoperative nausea and vomiting in patients undergoing general anesthesia remains unclear. This study aimed to explore whether the route of administration of acetaminophen affects postoperative analgesia, nausea, and vomiting in patients undergoing general anesthesia. METHODS: We included all randomized controlled trials investigating the effects of the route of administration of acetaminophen on postoperative pain, nausea, and vomiting in patients undergoing general anesthesia. Independent examiners reviewed the literature and extracted data, with disagreements resolved through negotiation or the involvement of a third party. The Cochrane risk assessment tool was used to evaluate the quality of the included randomized controlled trials. A narrative synthesis was conducted to summarize the qualitative information from the included studies. A meta-integration of quantitative data was performed using RevMan 5.4. RESULTS: Ten studies met the inclusion criteria. Eight studies assessed postoperative pain, whereas two assessed postoperative nausea and vomiting. Data from the eight studies assessing postoperative pain confirmed that there was no difference between intravenously and orally administered acetaminophen in adults (OR = -0.13; 95% CI, -0.36 to 0.11; p = 0.3). Data from the two studies assessing postoperative nausea and vomiting revealed no difference between intravenously and orally administered acetaminophen in adults (OR = 0.89; 95% CI, 0.64-1.25; p = 0.51). The included studies were of poor quality, with a heterogeneity of 68%. CONCLUSIONS: No differences in postoperative analgesia or postoperative nausea and vomiting were observed between the routes of administration (intravenous vs. oral) of acetaminophen in adult patients undergoing general anesthesia. There is a need for future large sample studies to increase the reliability of the results.

The toxic effects of Fluorene-9-bisphenol on porcine oocyte in vitro maturation.

Fluorene-9-bisphenol (9,9-bis(4-hydroxyphenyl)-fluorene [BHPF]) is a bisphenol A (BPA) substitute used in the production of "BPA-free" plastics, now has been identified is harmful to living organisms. Our previous study showed that BHPF impaired mouse denuded oocyte in vitro maturation. However, there is a question that whether BHPF is still able to affect oocyte maturation in the presence of dense cumulus cells. In the present study, we checked the toxic effects of BHPF on porcine oocyte maturation which is derived from COCs in vitro culture. Our results showed that BHPF (50 µM) inhibited the expansion of cumulus cells, led to a significant decrease in polar body extrusion (PBE). Importantly, BHPF resulted in abnormal spindle assembly, ATP level decrease, reactive oxygen species (ROS) accumulation and early apoptosis in porcine oocytes, which are all negative to oocyte maturation. Furthermore, BHPF also declined porcine oocyte quality by disturbing the cortical granules (CGs) distribution. In conclusion, our study showed that BHPF still inhibited oocyte maturation even in the presence of cumulus cells leading to abnormal spindle assembly, ATP decrease, increased ROS level, early apoptosis, and disturbed CGs distribution in porcine oocytes, and also indicates that BHPF has a wide range toxic effects on oocyte in different species.

A potential determinant role of adiponectin and receptors for the early embryo development in PCOS patients with obesity hinted by quantitative profiling.

OBJECTIVE: To identify the quantitative profiling of adiponectin and its receptors (AdipoR1, AdipoR2, and T-cadherin) in cumulus cells (CCs) and to evaluate their roles in the early embryo development of polycystic ovary syndrome (PCOS) patients, in part, with obesity. METHODS: Fifty-five subjects were divided into two groups according to the body mass index. Oocytes were further inseminated and only mature and normal fertilized oocytes (2PN) were included in this research. Real-time PCR and western blot were performed to identify adiponectin and its receptors in CCs. RESULTS: Adiponectin and receptors were ubiquitously expressed in CCs of PCOS and non-PCOS patients. The level of AdipoR2 in CCs from the oocytes yielding blastocyst after 5/6 days in vitro culture was markedly higher than in those from oocytes could not develop to blastocyst stage after Day 6, for non-obese or obese PCOS patients (0.1647 ± 0.0161 versus 0.0783 ± 0.0385, 0.1948 ± 0.0307 versus 0.1057 ± 0.0236, respectively, p < 0.05). In addition, only in patients with PCOS and concurrent obesity the AdipoR1 in CCs was considerably increased in CC-B+ compared with CC-B- subgroup (0.5162 ± 0.0371 versus 0.2448 ± 0.0333, p < 0.01). CONCLUSION: The development of early embryo was associated with the up-regulation of AdipoR1 and AdipoR2 in PCOS patients. Our results suggested that adiponectin could positively modulate embryo development in humans. Further investigations should be carried out to unlock the crucial role that adiponectin plays in embryo development.

Key subdomains in the C-terminal of cerebral dopamine neurotrophic factor regulate the protein secretion.

Cerebral dopamine neurotrophic factor (CDNF) is a novel evolutionary conserved neurotrophic factor (NTF) which can protect and repairs dopamine neurons in animal models of Parkinson's disease. The crystal structure of CDNF is dominated by eight α-helices and the 3-dimensional structure of CDNF consists of an N-terminal saposin-like domain and a C-terminal SAP-domain. In particular, the C-terminal domain contains two critical motifs, a CXXC motif and a putative ER retention signal sequences (KTEL) at the C-terminus, which indicate that CDNF may be involved in endoplasmic reticulum (ER) stress. In this study, we found that disrupting helix-7 in the C-terminal could significantly increase CDNF secretion. Moreover, we identified the 149aa-154aa is the key amino acids in helix-7. In all, these findings suggest that helix-7 in the C-terminal is important for CDNF secretion, which maybe potential affect CDNF function in ER stress.

Waist-to-height ratio is a better predictor of hypertension in women during recovery from anesthesia compared to BMI, waist-to-hip ratio, and waist circumference.

This was an observational study of patients with benign breast tumors intended to investigate and compare the predictive value of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) for hypertension in the recovery room. Logistic regression analysis was used to determine the association between these body fat anthropometric indices and hypertension. Receiver operating characteristic curve (ROC) analysis was performed to assess the comparative predictive ability. A total of 689 women were evaluated. Patients with BMI ≥28 (kg/m2), WC > 85 cm, WHR ≥0.82, and WHtR ≥0.5 had a significantly higher probability of increased systolic blood pressure (SBP) and diastolic blood pressure (DBP) than patients with less than threshold values (all P < 0.05). The areas under the ROC curve (AUC) of BMI, WC, and WHtR where all modestly significant (all AUC ≥0.65) and nearly identical at 0.6592, 0.65, and 0.6724, respectively. Conclusion: body fat anthropometric indices are useful predicting hypertension during recovery from general anesthesia in patients with benign breast tumors undergoing day surgery; WHtR outperformed the other indices and nearly identical.

Molecular fingerprint and machine learning enhance high-performance MOFs for mustard gas removal.

Chemical warfare agents (CWAs), epitomized by the notoriously used mustard gas (HD), represent a class of exceptionally toxic chemicals whose airborne removal is paramount for battlefield safety. This study integrates high-throughput computational screening (HTCS) with advanced machine learning (ML) techniques to investigate the efficacy of metal-organic frameworks (MOFs) in adsorbing and capturing trace amounts of HD present in the air. Our approach commenced with a comprehensive univariate analysis, scrutinizing the impact of six distinct descriptors on the adsorption efficiency of MOFs. This analysis elucidated a pronounced correlation between MOF density and the Henry coefficient in the effective capture of HD. Then, four ML algorithms were employed to train and predict the performance of MOFs. The Random Forest (RF) algorithm demonstrates strong model learning and good generalization, achieving the best prediction result of 98.3%. In a novel exploratory stride, we incorporated a 166-bit MACCS molecular fingerprinting (MF) to identify critical functional groups within adsorbents. From the top 100 MOFs analyzed, 22 optimal functional groups were identified. Leveraging these insights, we designed three innovative substructures, grounded in these key functional groups, to enhance HD adsorption efficiency. In this work, the combination of MF and ML could provide a new direction for efficient screening of MOFs for the capture of HD in the air. The outcomes of this study offer substantial potential to revolutionize the domain of CWA capture. This represents a significant stride toward developing practical solutions that enhance both environmental protection and battlefield security.

Humidity Enhances the Solid-Phase Catalytic Ability of a Bulk MOF-808 Metal-Organic Gel toward a Chemical Warfare Agent Simulant.

Zirconium-based metal-organic frameworks have emerged as promising materials for detoxifying chemical warfare agents (CWAs) due to their remarkable stability and porosity. However, their practical application is hindered by issues with their powder form and poor catalytic performance in solid-phase degradation. To address these challenges, herein, a granular MOF-808 metal-organic gel (G808) is prepared under optimized conditions for catalytic degradation of the simulant 2-chloroethyl ethyl sulfide (2-CEES), a sulfide blister agent, in a neat state under different humidity conditions. The detoxification performance of G808 toward 2-CEES is significantly enhanced as the content of water present increases. The half-life of 2-CEES decontaminated by G808 can be shortened to 816 s, surpassing those of many other benchmark materials. To confirm the mechanism of catalytic degradation, we used gas chromatography, gas chromatography-mass spectrometry, and theoretical calculations. The findings revealed that hydrolysis was the predominant route. Additionally, granular G808 was reusable and adaptable to high-moisture environments, making it an excellent protective material with practical potential.

Dual-State Fluorescent Probe for Ultrafast and Sensitive Detection of Nerve Agent Simulants in Solution and Vapor.

The development of fluorescent probes for detecting nerve agents has been the main concern focus of research because of their lethal toxicity for humans. Herein, a probe (PQSP) based on the quinoxalinone unit and the styrene pyridine group was synthesized and could visually detect a sarin simulant diethyl chlorophosphate (DCP) with excellent sensing properties in solution and solid states. Interestingly, PQSP showed an apparent intramolecular charge-transfer process by catalytic protonation after reacting with DCP in methanol, accompanied with the aggregation recombination effect. The sensing process was also verified by nuclear magnetic resonance spectra, scanning electron microscopy, and theoretical calculations. In addition, the papered test strips of loading probe PQSP exhibited an ultrafast response time within 3 s and high sensitivity with a limit of detection of 3 ppb for the detection of DCP vapor. Therefore, this research provides a designed strategy for developing the probes with dual-state emission fluorescence in solution and solid states for detecting DCP sensitively and rapidly, which can be fabricated as chemosensors to visually detect nerve agents in practice.

Carbendazim exposure inhibits mouse oocytes meiotic maturation in vitro by destroying spindle assembly.

Successful fertilization and early embryonic development heavily depend on the quality of the oocytes. Carbendazim (CBZ), a broad-spectrum fungicide, is widely available in the environment and has adverse effects on organisms. The present study focused on exploring the potential reproductive toxicity of CBZ exposure by investigating its effects on the maturation of mouse oocytes. The results demonstrated that although no disruptions were observed in the G2/M stage transition for meiosis resumption, CBZ did hinder the polar body extrusion (PBE) occurring during oocyte maturation. Cell cycle distribution analysis revealed that CBZ exposure interfered with the meiotic process, causing oocytes to be arrested at the metaphase I (MI) stage. The subsequent investigation highlighted that CBZ exposure impeded the spindle assembly and chromosomal alignment, which was linked to a decline in the level of p-MAPK. Additionally, CBZ exposure adversely affected the kinetochore-microtubule (K-MT) attachment, leading to the persistent activation of the spindle-assembly checkpoint (SAC). The study further noticed a substantial rise in the acetylation of α-tubulin and a reduction in spindle microtubule stability in CBZ-treated oocytes. In addition, the distribution pattern of estrogen receptor alpha (ERα) was altered in oocytes treated with CBZ, with abnormal aggregation on the spindles. CBZ exposure also resulted in altered histone modifications. A notable finding from this research was that the meiotic maturation of some oocytes remained unaffected even after CBZ treatment. However, during the ensuing metaphase II (MII) stage, these oocytes displayed anomalies in their spindle morphology and chromosome arrangement and diminished ability to bind to the sperm. The observations made in this study underscore the potential for CBZ to disrupt the meiotic maturation of oocytes, leading to a decline in the overall quality of oocytes.

Ultrafast Degradation and High Adsorption Capability of a Sulfur Mustard Simulant under Ambient Conditions Using Granular UiO-66-NH2 Metal-Organic Gels.

Zirconium-based metal-organic frameworks (Zr-MOFs) have been considered as prospective materials for the degradation of nerve chemical warfare agents (CWAs) but show poor catalytic performance toward blister agents. Moreover, the powder issues and the poor adsorption capability also remain as the major challenges for the application of Zr-MOFs in practical CWA detoxification. Herein, a series of defected granular UiO-66-NH2 metal-organic gels are synthesized via adjusting the amount of added concentrated hydrochloric acid for the decontamination of 2-chloroethyl ethyl sulfide (2-CEES), a sulfur mustard simulant. The half-life of 2-CEES decontaminated by defected granular UiO-66-NH2 metal-organic gels can be shortened to 7.6 min, which is the highest reported value for MOFs under ambient conditions. The mechanism of decontamination is that the amino group on the linkers in UiO-66-NH2 MOGs undergoes a substitution reaction with 2-CEES to yield 2-(2-(ethylthio)ethylamino)terephthalic acid, which is less toxic and fixed in the frameworks. The recycling test corroborates that the granular UiO-66-NH2 xerogels possess good stability and reusability. Static adsorption and desorption tests show that UiO-66-NH2 xerogels possess a high 2-CEES vapor adsorption capacity of 802 mg/g after exposure for 1 d and only 28 wt % desorption capacity after air exposure for 7 d. The dual function of ultrafast degradation and high adsorption capability provide a firm foundation for using UiO-66-NH2 xerogels as a future protection media.

Incorporation of Laboratory Test Biomarkers Into Dual Antiplatelet Therapy Score Improves Prediction of Ischemic and Bleeding Events in Post-percutaneous Coronary Intervention Patients.

This study aimed to examine the performance of the dual antiplatelet therapy (DAPT) score in two retrospective cohorts of post-percutaneous coronary intervention (PCI) patients and to explore whether incorporating additional biomarkers could further improve the predictive power of the DAPT score. In a retrospective derivation cohort of 4,798 PCI patients, the validity of DAPT score for stratifying ischemic/bleeding risks was explored. Then, the association between the baseline status of 54 laboratory test biomarkers and ischemic/bleeding events was revealed while adjusting for the DAPT score. Combinations of individual laboratory test biomarkers that were significantly associated with ischemic/bleeding events were explored to identify the ones that improved discrimination of ischemic and bleeding events when incorporated into DAPT score. Finally, the impact of the combination of biomarkers with DAPT score was validated in an independent retrospective validation cohort of 1,916 PCI patients. Patients with a high DAPT score (DAPT score ≥ 2) had significantly higher risk of ischemic events and significantly lower risk of bleeding than patients with a low DAPT score (DAPT score < 2). Moreover, the addition of aspartate aminotransferase (AST) and red cell distribution width CV (RDW-CV) into the DAPT score further improved discrimination of ischemia and bleeding. Furthermore, the incremental predictive value of AST + RDW-CV maintained with measurements was updated at post-baseline time points. DAPT score successfully stratified the risks of ischemia/bleeding post PCI in the current cohorts. Incorporation of AST + RDW-CV into the DAPT score further improved prediction for both ischemic and bleeding events.

Bromoacetic acid impairs mouse oocyte in vitro maturation through affecting cytoskeleton architecture and epigenetic modification.

As a major public health achievement, disinfection of drinking water significantly decreases outbreaks of waterborne disease, but produces drinking water disinfection by-products (DBPs) unfortunately. The haloacetic acids (HAAs) including bromoacetic acid (BAA), the second major class of DBPs, are considered as a global public health concern. BAA has been identified as cytotoxic, genotoxic, mutagenic, carcinogenic, and teratogenic in somatic cells. However, the toxic effects of BAA on oocyte maturation remain obscure. Herein, we documented that exposure to BAA compromised mouse oocyte maturation in vitro, causing blocked polar body extrusion (PBE). Meiotic progression analysis demonstrated that exposure to BAA induced the activated spindle assembly checkpoint (SAC) mediated metaphase I (MI) arrest in oocytes. Further study revealed that exposure to BAA resulted in the hyperacetylation of α-tubulin, disrupting spindle assembly and chromosome alignment, which is responsible for the activation of SAC. Besides, the organization of actin, the other major component of cytoskeleton in oocytes, was disturbed after BAA exposure. In addition, exposure to BAA altered the status of histone H3 methylation and 5 mC, indicative of the damaged epigenetic modifications. Moreover, we found that exposure to BAA induced DNA damage in a dose-dependent manner in oocytes. Collectively, our study evidenced that exposure to BAA intervened mouse oocyte maturation via disrupting cytoskeletal dynamics, damaging epigenetic modifications and inducing accumulation of DNA damage.

Synthesis of macroscopic monolithic metal-organic gels for ultra-fast destruction of chemical warfare agents.

The potential threat that has originated from chemical warfare agents (CWAs) has promoted the development of advanced materials to enhance the protection of civilian and military personnel. Zr-based metal-organic frameworks (Zr-MOFs) have recently been demonstrated as excellent catalysts for decomposing CWAs, but challenges of integrating the microcrystalline powders of Zr-MOFs into monoliths still remain. Herein, we report hierarchically porous monolithic UiO-66-X xerogels for the destruction of CWAs. We found that the UiO-66-NH2 xerogel with a larger pore size and a higher surface area than the UiO-66-NH2 powder possessed better degradability of 2-chloroethyl ethyl sulfide (2-CEES), which is a sulfur mustard simulant. These UiO-66-X xerogels exhibit outstanding performance for decomposing CWAs. The half-lives of vesicant agent sulfur mustard (HD) and nerve agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) are as short as 14.4 min and 1.5 min, respectively. This work is, to the best of our knowledge, the first report on macroscopic monolithic UiO-66-X xerogels for ultrafast decomposition of CWAs.

A Comprehensive Review on Water Diffusion in Polymers Focusing on the Polymer-Metal Interface Combination.

Water diffusion in polymers is relevant to a broad range of physicochemical phenomena and technological processes. Although many fields contributed to rapid progress in the fundamental knowledge of water-polymer interactions, detailed understandings come mainly from interpreting numerous experiments. These studies showed that a remarkably rich variety of diffusion forms between water and even seemingly simple polymers. In this review, focusing on the gravimetric and capacitance method, we discuss contradictions and problems existing for water diffusion in polymers in detail from perspectives of experiments and models, focusing on the analysis of error derived from widely used methods, especially for the Brasher-Kingsbury equation. We also provide a perspective on outstanding problems, challenges, and open questions, including water clusters, relaxation, and electrochemical reactions at the metal/polymer interface, as well as expanding the theoretical prospective.

Advanced maternal age alters expression of maternal effect genes that are essential for human oocyte quality.

To investigate the effects of maternal age on the quality of oocytes, we used single-cell RNA sequencing to detect global gene transcriptome and identify key genes affected by advanced age in human mature oocytes. We isolated mRNA from mature oocytes obtained from IVF or ICSI patients (three oocytes from younger (≤30 years) and three oocytes from older (≥40 years) patients for scRNA-seq. We identified 357 genes differentially expressed between matured oocytes from older and younger women's. The up-regulated genes were significantly enriched with annotations related to transcriptional activation, oxidative stress and immune function, while down-regulated genes were enriched with catalytic activity. The key candidate gene TOP2B was found by protein interaction network analysis, and knockdown verification on younger mouse matured oocytes showed that TOP2B was a key gene affecting the oocyte quality and early embryo development. These results will contribute new knowledge on the molecular mechanisms of female ovary aging and establish a criterion to evaluate the quality of oocytes in women with advanced maternal age.

Triclocarban exposure affects mouse oocyte in vitro maturation through inducing mitochondrial dysfunction and oxidative stress.

Triclocarban (TCC), a broad-spectrum lipophilic antibacterial agent, is the main ingredient of personal and health care products. Nonetheless, its ubiquitous presence in the environment has been established to negatively affect the reproduction in humans and animals. In this work, we studied the possible toxic effects of TCC on mouse oocytes maturation in vitro. Our findings revealed that TCC-treated immature mouse oocytes had a significantly reduced rate of polar body extrusion (PBE) compared to that of control. Further study demonstrated that the cell cycle progression and cytoskeletal dynamics were disrupted after TCC exposure, which resulted in the continuous activation of spindle assembly checkpoint (SAC). Moreover, TCC-treated oocytes had mitochondrial damage, reduced ATP content, and decreased mitochondrial membrane potential (MMP). Furthermore, TCC exposure induced oxidative stress and subsequently triggered early apoptosis in mouse oocytes. Besides, the levels of histone methylation were also affected, as indicated by increased H3K27me2 and H3K27me3 levels. In summary, our results revealed that TCC exposure disrupted mouse oocytes maturation through affecting cell cycle progression, cytoskeletal dynamics, oxidative stress, early apoptosis, mitochondria function, and histone modifications in vitro.

Isobutylparaben Negatively Affects Porcine Oocyte Maturation Through Increasing Oxidative Stress and Cytoskeletal Abnormalities.

As a member of parabens (PBs), Isobutylparaben (IBP) has a broad-spectrum antimicrobial activity and widely used in personal care products and cosmetics. Recent studies have indicated that usage of IBP poses a potential threat to reproductive health. In this study, we aimed to reveal the effects of acute exposure to IBP on the meiotic maturation of porcine cumulus oocyte complexes. Initial study showed that 200 µM of IBP significantly reduced the rate of the first polar body extrusion with no significant effect on cumulus cell expansion; however, 400 µM of IBP could significantly affect both. Further research revealed that abnormal spindles, misalignment chromosomes, and aberrant distributed actin filaments were detected in IBP-treated oocytes, which indicates that the cytoskeleton architecture of oocyte could be the target of IBP. At the same time, ROS level and apoptosis rate of oocyte were significantly increased by IBP exposure. Moreover, the levels of H3K9me3 and H3K27me3 were significantly induced in oocytes by IBP. Collectively, these results demonstrate that acute exposure to IBP could disrupt porcine oocyte maturation through affecting cytoskeleton, oxidative stress, viability and epigenetic modification. Environ. Mol. Mutagen. 2020. © 2020 Wiley Periodicals, Inc.

Diethylstilbestrol exposure disrupts mouse oocyte meiotic maturation in vitro through affecting spindle assembly and chromosome alignment.

An adverse tendency induced by the environmental estrogens in female reproductive health is one serious problem worldwide. Diethylstilbestrol (DES), as a synthetic estrogen, is still used as an animal growth stimulant in terrestrial livestock and aquaculture illegally. It has been reported to negatively affect ovarian function and oogenesis. Nevertheless, the mechanism and toxicity of DES on oocyte meiotic maturation are largely unknown. Herein, we found that DES (40 µM) intervened in mouse oocyte maturation and first polar body extrusion (PBE) was decreased in vitro. Cell cycle analysis showed meiotic process was disturbed with oocytes arrested at metaphase I (MI) stage after DES exposure. Further study showed that DES exposure disrupted the spindle assembly and chromosome alignment, which then continuously provoke the spindle assemble checkpoint (SAC). We also observed that the acetylation levels of α-tubulin were dramatically increased in DES-treated oocytes. In addition, the dynamics of actin were also affected. Moreover, the distribution patterns of estrogen receptor α (ERα) were altered in DES-treated oocyte, as indicated by the significant signals accumulation in the spindle area. However, ERα inhibitor failed to rescue the defects of oocyte maturation caused by DES. Of note, the same phenomenon was observed in estrogen-treated oocytes. Collectively, we showed that DES exposure lead to the oocyte meiotic failure via impairing the spindle assembly and chromosome alignment. Our research is helpful to understand how environmental estrogen affects female germ cells and contribute to design the potential therapies to preserve fertility especially for occupational exposure.