Reproductive Toxicity Research Articles

Aflatoxin Exposure-Caused Male Reproductive Toxicity: Molecular Mechanisms, Detoxification, and Future Directions

Widespread endocrine disorders and infertility caused by environmental and food pollutants have drawn considerable global attention. Aflatoxins (AFTs), a prominent class of mycotoxins, are recognized as one of the key contributors to environmental and food contamination. Aflatoxin B1 (AFB1) is the most potent and toxic pollutant among them and is known to cause multiple toxic effects, including neuro-, nephro-, hepato-, immune-, and genotoxicity. Recently, concerns have been raised regarding AFB1-induced infertility in both animals and humans. Exposure to AFB1 can disrupt the structure and functionality of reproductive organs, leading to gametogenesis impairment in males, subsequently reducing fertility. The potential molecular mechanisms have been demonstrated to involve oxidative stress, cell cycle arrest, apoptosis, inflammatory responses, and autophagy. Furthermore, several signaling pathways, including nuclear factor erythroid 2-related factor 2; NOD-, LRR-, and pyrin domain-containing protein 3; nuclear factor kappa-B; p53; p21; phosphoinositide 3-kinase/protein kinase B; the mammalian target of rapamycin; adenosine 5′-monophosphate-activated protein kinase; and mitochondrial apoptotic pathways, are implicated in these processes. Various interventions, including the use of small molecules, Chinese herbal extracts, probiotic supplementation, and camel milk, have shown efficacy in ameliorating AFB1-induced male reproductive toxicity, by targeting these signaling pathways. This review provides a comprehensive summary of the harmful impacts of AFB1 exposure on male reproductive organs in mammals, highlighting the potential molecular mechanisms and protective agents.

Recent advances in the toxicological effects of difenoconazole: A focus on toxic mechanisms in fish and mammals.

The toxicological study of pesticides at sub-lethal and environment-relevant concentrations has become increasingly crucial for human and environmental health. Toxic mechanisms of agrochemicals contribute to discovering green pesticides, assessing the hazards of pesticides comprehensively, and supporting legitimate regulatory decisions. However, the toxicological effects of difenoconazole are not yet fully understood despite being frequently detected in fruits, vegetables, waters, and soils and posing hazards to humans and the environment. This lack of knowledge could lead to flawed risk assessment and administrative oversight. Thus, the review aimed to provide some investigation perspectives for clarifying the toxicological effects of difenoconazole by synthesizing the toxic data of difenoconazole on various organisms, such as bees, Daphnia magna, fish, earthworms, mammals, and plants and summarizing the toxicological mechanisms of difenoconazole, especially in fish and mammals from peer-reviewed publications. Evidence revealed that difenoconazole caused multiple toxicological effects, including developmental toxicity, reproductive toxicity, endocrine disruption effects, neurotoxicity, and transgenerational toxicity. The toxic mechanisms involved in metabolic disturbance, oxidative stress, inflammation, apoptosis, and autophagy by activating reactive oxygen species-mediated signaling pathways and mitochondrial apoptosis routes, disturbing amino acids, lipid, and nucleotide metabolism, and regulating gene transcription and expression in mammals and fish. Based on the review, further studies better focus on the toxic differences of difenoconazole stereoisomers, the toxicological effects of transformation products of difenoconazole, and the mechanism of action of difenoconazole on sex-specific endocrine disruption effects, intestinal damage, and gut dysbacteriosis for its hazard assessment and management synthetically.

Progress in the study of toxic effects of drugs on the male reproductive system

This paper provides a comprehensive summary of the toxic effects of drugs on the male reproductive system, with a special focus on the mechanisms of testicular and sperm damage caused by chemotherapeutic agents, antibiotics, and immunosuppressants. Drug-induced reproductive toxicity usually manifests through multiple pathways including direct injury, interference with hormone regulation, oxidative stress, and DNA damage. These mechanisms can lead to impaired spermatogenesis, decreased testicular function, and long-term infertility, thereby seriously affecting male reproductive health. Specifically, chemotherapeutic drugs, such as cisplatin and cyclophosphamide, have been widely documented to cause direct damage to the testes, leading to significant decreases in sperm quantity and quality. Antibiotics and nonsteroidal anti-inflammatory drugs also negatively affect reproductive function by affecting mitochondrial function and inducing oxidative stress in the testicular cells. Although important advances have been made in recent years in the study of drug-induced reproductive toxicity, further exploration is needed to assess the variability of individual responses to drugs and develop long-term protective measures. Future research should focus on developing accurate toxicity assessment methods, customized therapeutic regimens, and enhanced fertility protection strategies, such as the use of antioxidants and methods for the cryopreservation of testes and sperm. Interdisciplinary collaboration will provide new solutions for balancing disease treatment and fertility preservation, especially in the use of high-risk drugs, such as anticancer therapies, where achieving both efficacy and reproductive health will be an important clinical challenge.

Prediction model of male reproductive function damage caused by CHOP chemotherapy regimen for non-Hodgkin's lymphoma.

The CHOP combined chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) is commonly used to treat non-Hodgkin Lymphoma (NHL). While these drugs are effective for cancer treatment, they may have side effects on the reproductive system that are poorly studied. This study used a mouse model to investigate the mechanisms of reproductive function impairment induced by the CHOP regimen and developed a predictive model for assessing reproductive damage with a non-invasive procedure. From 2022 to 2023, we statistically analyzed the changes of reproductive function of NHL patients before and after receiving CHOP regimen in the First Affiliated Hospital of Xiamen University. The NHL mouse model was established and divided into CHOP treatment group and control group. The weight of testis and epididymis, sperm quality and motility were compared between the two groups. Histopathological examination of testicular tissue was performed to determine pathological changes. ELISA was used to measure the expression of cytokines and cytokine pathways in serum, protein expression was analyzed by immunohistochemistry, and protein and mRNA levels of cytokines and pathways were evaluated by Western blotting and qPCR. Using stepwise regression method to select important factors, a prediction model of reproductive system damage was constructed. Fifty-two NHL patients included in the questionnaire showed significant reproductive system damage after CHOP regimen treatment. The weight of testis and epididymis, as well as the number and vitality of sperm in the mouse model treatment group were significantly lower than those in the control group. Serum LH, FSH, estradiol and progesterone levels decreased significantly, while inhibin B levels increased significantly. There was no significant change in testosterone or prolactin levels. Inflammatory markers such as CSF-1, IL-1, IL-6, TGF-β1 and GDNF increased significantly, while the level of SOD1 decreased significantly. Immunohistochemical staining analysis showed that CAMP, Caspase3, CSF-1, GDNF, IL-1, IL-6, PRKACB, TGF-β1 and TXNDC5 were all expressed in spermatocytes, and the expression of therapeutic histones was significantly higher than that of the control group. Western blot analysis further detected the protein expression, and QPCR detected the mRNA content. The results showed that the expression of histone and mRNA in the treatment group was significantly higher than that in the control group. Stepwise regression method determined that estradiol (E2) was the most important variable in the prediction model, and the AUC for predicting reproductive damage was 1. The CHOP regimen induces male reproductive toxicity, potentially mediated through alterations in hormone levels and increased expression of inflammatory cytokines and oxidative stress. Using E2 as the sole predictor in the model accurately predicts the extent of reproductive damage, offering a non-invasive method for detecting reproductive system damage.

Transcriptome analysis reveals the molecular mechanisms of neonicotinoid acetamiprid in Leydig cells.

At present, the reproductive toxicology of neonicotinoids has received greater attention, however, its potential mechanisms are still not fully understood. Acetamiprid (ACE) is a new-generation neonicotinoid and has become a ubiquitous contaminant in the environment. This study aimed to investigate the toxic effects of ACE in TM3 Leydig cells based on transcriptome analysis. The viability and apoptosis of TM3 cells exposed to different concentrations of ACE were assessed by CCK8 and flow cytometry, respectively. After ACE exposure, transcriptome analysis was performed to screen differential expression genes (DEGs), followed by qPCR verification. Results showed that ACE exposure resulted in a time- and dose-dependent decrease in the viability of TM3 cells (p < .05). ACE also exerted a dose-dependent pro-apoptotic effect on TM3 cells. Results of RNA-seq showed that 1477 DEGs were obtained, of which 539 DEGs were up-regulated and 938 DEGs were down-regulated. GO and KEGG analyses of DEGs showed that DNA replication and cell cycle might be the key mechanisms for the cytotoxicity of ACE. qPCR results demonstrated that Mdm2, Cdkn1a (p21) and Gadd45 were significantly increased, and Pcna, Ccna2 (CycA), Ccnb1 (CycB), Ccne1 (CycE), and Cdk1 were significantly decreased, indicating that ACE exposure might promote G1/S and G2/M cell cycle arrest. Additionally, FoxO, p53, and HIF-1 signaling pathways and ferroptosis might play important roles in ACE-induced reproductive toxicity. Collectively, this study provides new perspectives into the mechanism of ACE-induced reproductive toxicity and lays a theoretical foundation for the in-depth study of non-target toxicity mechanisms of neonicotinoid insecticides.

Enhanced Prenatal and Postnatal Development Study in Marmoset Monkeys Following Administration of Felzartamab.

Felzartamab is a recombinant fully human immunoglobulin G1 anti-CD38 monoclonal antibody under clinical investigation for immune-mediated diseases. In support of felzartamab clinical development, toxicology studies were conducted in marmoset monkeys, which was the most relevant species based on CD38 binding affinity, pharmacologic activity, and target expression. The felzartamab toxicology program included an enhanced prenatal and postnatal development (ePPND) study to identify potential reproductive and postnatal development risks. In this ePPND study, pregnant marmoset monkeys were randomized to receive vehicle (0mg/kg) or felzartamab at two dose levels (15mg/kg and 75mg/kg) twice per week until parturition, and maternal animals and infants were evaluated for 6 months thereafter. Felzartamab exposure was confirmed in maternal animals and infants in both dosing groups. Overall, felzartamab was well tolerated by pregnant animals at the evaluated doses, with no effect on body weight or body weight gain during pregnancy. No felzartamab-related effects on pregnancy loss or stillbirth rate were observed, and litter counts and numbers of liveborn infants were similar between the vehicle and felzartamab groups. Among infants, there were no felzartamab-related malformations or variations in external anatomy or skeletal morphology and no felzartamab-related observations in histopathology, hematologic and immune cell development, or humoral immune response to vaccination. In conclusion, among pregnant marmoset monkeys dosed with felzartamab, the lack of reproductive toxicity and felzartamab-related effects on offspring supports the clinical evaluation of felzartamab in women of childbearing potential and further demonstrates the suitability of the marmoset monkey for ePPND studies.

Dietary exposure to di (2-ethylhexyl) phthalate (DEHP) for 6months alters markers of female reproductive aging in mice.

The female reproductive system ages before any other physiological system, making it a sensitive indicator of aging. Early reproductive aging is associated with the early onset of infertility and an increased risk of several diseases. During aging, systemic and reproductive oxidative stress and inflammation levels increase through inflammasome activation, leading to ovarian follicle loss. Other markers of reproductive aging include increased fibrosis and shortening of telomeres in ovarian cells. The factors that accelerate reproductive aging are unclear, but likely involve exposure to endocrine-disrupting chemicals such as phthalates. Di(2-ethylhexyl) phthalate (DEHP) is a widely used phthalate and humans are exposed to it daily. Several studies show that DEHP induces reproductive toxicity by affecting estrous cyclicity, follicle numbers, and hormone levels. However, little is known about the mechanisms underlying DEHP-induced early onset of reproductive aging. Thus, this study tested the hypothesis that dietary exposure to DEHP induces early reproductive aging by affecting inflammation, fibrosis, and the expression of telomere regulators and antioxidant enzymes. Adult CD-1 female mice were exposed to vehicle (corn oil) or DEHP (0.5, 1.5, or 1500ppm) via the chow for six months. Exposure to DEHP increased the expression of antioxidant enzymes and Casp3, increased expression of telomere-associated genes, and increased fibrosis levels in the ovary. In addition, DEHP exposure for 6months altered ovarian and systemic inflammatory status. Collectively, our novel data suggest that 6-month dietary exposure to DEHP may accelerate reproductive aging by affecting several reproductive aging markers in female mice.

Health Implications of Depleted Uranium: An Update.

Depleted uranium (DU), as a heavy metal material extensively utilized in the industrial sector, poses potential health risks to humans through various exposure pathways, including inhalation, ingestion, and dermal contact. To comprehensively understand the toxicological hazards of DU, this study conducted a literature search in the Web of Science Core Collection database using "DU" and "toxicity" as keywords, covering the period from January 2000 to December 2023. A total of 65 papers related to human, animal, or cellular studies on DU were included. This review delves into the latest research advancements on the origin and toxicokinetics of DU, as well as its pulmonary toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, hepatotoxicity, reproductive toxicity, cancer, bone toxicity, and hematological toxicity. The aim of this review is to gain a deeper understanding of the health hazards posed by DU, which is of significant importance for formulating corresponding protection strategies and measures.

Research Progress on Pharmacological and Toxicological Effects of Bavachin

Objective: To analyze and summarize the latest research progress regarding pharmacological and toxicological effects of bavachin. Methods: Through retrieval of all bavachin-related reports on pubmed, CNKI, Wanfang database and other databases, the pharmacologic and toxicological effects of bavachin were sorted out and concluded accordingly. Results: The study showed that bavachin had a wide range of pharmacological activities, including estrogen-like, anti-inflammatory, anti-tumor, immunoregulatory, anti-diabetes and its complications effects. The toxicological effects of bavachin were mainly manifested in three aspects: hepatotoxicity, reproductive toxicity and nephrotoxicity. Conclusions: Bavachin has the characteristics of multi-function and multi-target monomer similar to traditional Chinese medicine, and broad application prospects, but also has certain toxicological effects. How to avoid toxicity, as well as enhance strengths and avoid weaknesses is the direction of development and utilization of bavachin. This review provides reference for further development and utilization of bavachin.

Polystyrene microplastics cause reproductive toxicity in male mice

Microplastics are a common environmental pollutant that disrupts the reproductive system of living organisms. We investigated the reproductive toxicity of 2μm polystyrene microplastics (PS-MPs) in mice and treated them with PS-MPs for 6 weeks. We demonstrated that PS-MPs decreased the gonadosomatic index and the serum concentration of pituitary-testicular axis hormones (Follicle-stimulating hormone, Luteinizing hormone, and testosterone). The PS-MPs treatment also reduced viable epididymal sperm number and sperm motility. Our results also demonstrated a marked decrease in tubular differentiation index, spermatogenesis index, repopulation index, and steroidogenic foci. The PS-MPs treated mice demonstrated marketed tissue damage in the testis. We also found that reproductive abnormality in PS-MPs treated mice accompanied by reduced antioxidant capacity elevated oxidative stress, and, elevated apoptotic signaling. It was observed that Endoplasmic reticulum (ER) stress markers, including GRP78 and Chop, were upregulated. Based on these findings, oxidative stress and endoplasmic reticulum stress may contribute to the decline in the steroidogenic function of Leydig cells with PS-MPs treated.

An advanced sensitive detection method for internal and external exposures assessment of para-phenylenediamines and their quinone derivatives based on hierarchical pore-structured nitro-microporous organic networks

para-Phenylenediamines (PPDs) and their quinone derivatives (PPD-Qs) are emerging pollutants that are associated with neurotoxicity, reproductive toxicity, and genetic toxicity, raising significant public health concerns globally. In this study, a novel hierarchical pore-structured nitro-microporous organic networks (NO2-MONs) characterized by multiple adsorption interactions and rapid mass transfer rates was synthesized. Model fitting and adsorption experiments confirmed diverse interaction mechanisms, including pore effects, hydrogen bonding, π-π stacking, and hydrophobic interactions. Utilizing these advantages, NO2-MONs-coated solid-phase microextraction fibers facilitated the effective extraction of trace PPDs and PPD-Qs. Subsequently, a highly sensitive analytical approach was developed for detecting trace amounts of PPDs and PPD-Qs using GC-MS/MS analysis. This method significantly improved upon existing techniques, addressing the low accuracy associated with current semi-quantitative methods and enhancing sensitivity by two orders of magnitude. Notably, the achieved detection limits ranged from 0.38 to 2.6 pg mL−1, with recovery rates between 75.7 % and 117.5 % (RSD ≤ 9.8 %). This proposed approach provides technical support for investigating concentration-dose-effect relationships related to the environmental presence of PPDs and PDD-Qs, facilitating the development of relevant regulatory standards.

Sildenafil citrate induces prostatic hyperplasia in BPH model rats and aged rats

Erectile dysfunction (ED), a prevalent disease among middle-aged and elderly males, significantly impacts both patient and partner quality of life. Phosphodiesterase type 5 inhibitor (PDE5i) represents an effective therapeutic method for ED. Given their widespread global utilization, concerns arise regarding potential reproduction-related problems arising from clinical use. During the extensive development of PDE5i, we speculated that the potential of these inhibitors to variably induce prostatic hyperplasia, but this field remains unexplored. In order to verify the male reproductive toxicity of PDE5i, sildenafil citrate at doses of 5, 10 and 20 mg/kg was administered in BPH model rats and aged rats. Anatomical and pathological analyses indicate a compelling association between sildenafil citrate administration and the promotion of prostatic hyperplasia in both BPH model rats and aged rats. Serum analysis showed that serum prostate-binding protein (PBP) exhibited a non-significant but increasing trend following administration of sildenafil citrate to BPH model rats. Furthermore, significant increase in serum levels of E2 and T, as well as T in dorsal lobe prostate tissue of aged rats, were observed compared to the model control group. These results confirm the hypothesis that sildenafil citrate has reproductive toxicity in males.

Role of Rab proteins in PFOA-induced changes in boar sperm motility and capacitation

Perfluorooctanoic acid (PFOA), a pervasive environmental contaminant, elicits adverse effects on sperm functions, including sperm motility and capacitation status. However, the specific mechanisms by which PFOA disrupts sperm functions during capacitation remain poorly elucidated. Therefore, this study aimed to investigate the molecular mechanisms underlying the PFOA-induced inhibition of sperm motility and capacitation in boar spermatozoa by focusing on Ras-related (Rab) proteins, which regulate membrane trafficking and play key roles in male sperm development, acrosome formation, and the acrosome reaction. Results showed significant reductions in sperm motility and various kinematic parameters following PFOA exposure. Correlation analysis revealed that Rab14 was positively correlated with dance mean (DNM) and negatively correlated with wobble (WOB), indicating that PFOA might affect sperm motility through Rab14 and potentially lead to reduced pregnancy rates. Differences in Rab25 were positively correlated with differences in total motility (MOT), progressive motility (PRG), linearity (LIN), and mean angular displacement (MAD), suggesting that PFOA might influence sperm motility by altering Rab25. Differences in Rab34 were positively correlated with differences in acrosome-reacted spermatozoa, implicating its role in the acrosome reaction. These findings provided insights into the molecular mechanism of PFOA-induced reproductive toxicity and highlighted the function of Rab proteins as biomarkers for the assessment of the effects of similar environmental toxins on male fertility.

RIFM fragrance ingredient safety assessment, 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone, CAS Registry number 61315-75-1

The existing information supports the use of this material as described in this safety assessment.4-(4-Methyl-3-penten-1-yl)-2(5H)-furanone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, photoirritation/photoallergenicity, skin sensitization, and environmental safety. Data show that 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone is not mutagenic. The clastogenicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for the genotoxicity endpoint material, and the exposure to 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone is below the TTC (0.0025 μg/kg/day). The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the TTC for a Cramer Class III material, and the exposure to 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). The skin sensitization endpoint was completed using the Dermal Sensitization Threshold (DST) for reactive materials (64 μg/cm2); exposure is below the DST. The photoirritation/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone is not expected to be photoirritating/photoallergenic. The environmental endpoints were evaluated; for the hazard assessment based on the screening data, 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone is not Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards. For the risk assessment, 4-(4-methyl-3-penten-1-yl)-2(5H)-furanone was not able to be risk screened as there were no reported volumes of use (VoU) for either North America or Europe in the 2019 IFRA Survey.

Copper Oxide Nanoparticles Impair Mouse Preimplantation Embryonic Development through Disruption of Mitophagy-Mediated Metabolism.

Copper oxide nanoparticles (CuONPs) have been widely applied, posing potential risks to human health. Although the toxicity of CuONPs on the liver and spleen has been reported, their effects on reproductive health remain unexplored. In this study, we investigate the effects of CuONPs on embryonic development and their potential mechanisms. Our results demonstrate that CuONPs exposure impairs mouse preimplantation embryonic development, particularly affecting the morula-to-blastocyst transition. Additionally, CuONPs were found to reduce the pluripotency of the inner cell mass (ICM) and mouse embryonic stem cells (mESCs). Mechanistically, CuONPs block autophagic flux and impair mitophagy, leading to the accumulation of damaged mitochondria. This mitochondrial dysfunction leads to reduced tricarboxylic acid (TCA) cycle activity and decreased α-ketoglutarate (α-KG) production. Insufficient α-KG induces the failure of DNA demethylation, reducing corresponding chromatin accessibility and consequently inhibiting ICM-specific genes expressions. Similar reduced development and inhibitions of pluripotency gene expression were observed in CuONPs-treated human blastocysts. Moreover, in women undergoing assisted reproductive technology (ART), a negative correlation was found between urinary Cu ion concentrations and clinical outcomes. Collectively, our study elucidates the mitophagy-mediated metabolic mechanisms of CuONPs embryotoxicity, improving our understanding of the potential reproductive toxicity associated with it.

Assessment of reproductive, genotoxic, and cytotoxic effects of leachate-contaminated water in male mice

Leachate-contaminated water (LCS) poses significant health risks due to its heavy metal content and altered physicochemical properties. This study examined the physicochemical parameters and heavy metal levels in LCS and assessed its reproductive toxicity, genotoxicity, and cytotoxic effects in exposed mice. Groups of mice (n = 5) were orally administered 100 μL of 30 % and 70 % LCS (v/v) twice daily for 35 days. Drinking water served as a negative control, and cyclophosphamide (Cyp) (20 mg/kg bw) as a positive control. On day 36, the mice were weighed, sacrificed, and their testicular weight, sperm count, sperm morphology, viability, acrosome integrity, and serum testosterone were examined. Oxidative stress in the testes, histopathological changes, and serum markers for liver and kidney function (SGOT, SGPT, and creatinine) were also assessed. Genotoxic effects were evaluated using a micronuclei (MN) assay. Analysis of the leachate showed altered physicochemical parameters and elevated heavy metal levels. Exposure to LCS led to a significant decrease in relative testis weight, sperm count, normal sperm morphology, viability, acrosome integrity, and serum testosterone levels. It also caused a notable increase in MDA levels and a decrease in catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) levels, along with histological changes in the testes of LCS-treated mice compared to controls. Additionally, there was a significant rise in MN formation in RBCs and elevated levels of liver enzymes and creatinine, indicating liver and renal toxicity. Histological alterations in the liver and kidneys were also observed in LCS-exposed mice. These findings suggest that LCS induces reproductive toxicity, genotoxicity, and cytotoxicity in male subjects.

The mechanistic pathway induced by fenpropathrin toxicity: Oxidative stress, signaling pathway, and mitochondrial damage.

Fenpropathrin (FNP) is a kind of insecticide and acaricide known as pyrethroid. It is very effective, has a wide range of activities, and works quickly. Internationally, it is commonly considered the most powerful pyrethroid insecticide. Nevertheless, an increasing amount of data indicates a substantial link between Fenpropathrin and adverse effects on nontarget species, including liver toxicity, kidney toxicity, nerve damage, and reproductive toxicity. Oxidative stress plays a vital role in the toxicity of fenpropathrin, in addition to its mechanical mechanism. This study offers a thorough examination of the harmful effects of Fenpropathrin on oxidative and mitochondrial processes, as well as the signaling pathways involved in these effects. The significant impact of oxidative stress emphasizes the toxicity of Fenpropathrin.

Ginkgo biloba extract alleviates deltamethrin-induced testicular injury by upregulating SKP2 and inhibiting Beclin1-independent autophagy

BackgroundMale infertility is a worldwide concern that is associated with a decline in sperm quality. Environmental pollutants such as deltamethrin (DM) have harmful effects on male reproductive organs. By maintaining intracellular redox homeostasis, ginkgo biloba extract (GBE) can alleviate male reproductive dysfunction. However, research on the mechanisms by which GBE alleviates reproductive toxicity induced by DM is limited. PurposeIn this study, we investigated whether GBE can alleviate DM-induced testicular and Sertoli cell reproductive toxicity by modulating SKP2 and Beclin1, thus providing a theoretical basis for the development of novel therapeutic approaches. Study DesignWe explored the role of GBE in mitigating DM-induced testicular damage, with a specific focus on the intricate involvement of ubiquitination and autophagy. MethodsAn experimental model was constructed using ICR male mice and the TM4 cell line. Tissue, cellular, and sperm morphological changes were observed through methods such as Hematoxylin and Eosin (H&E) staining, Periodate-Schiff (PAS) staining, ultrastructural observation, immunohistochemistry, and immunofluorescence. Enzyme and hormone levels were measured, and gene and protein levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting techniques. ResultsIn vivo experiments showed that DM exposure led to decreased sex hormone levels, increased seminiferous tubule diameter and impaired spermatogenesis. Meanwhile, DM exposure was found to decrease ubiquitination levels, leading to mitochondrial damage and further escalation of mitochondrial autophagy. Furthermore, in the DM-induced cell model, the upregulation of Beclin1 expression was associated with the inhibition of the ubiquitin‒proteasome system (UPS) and SKP2, thereby exacerbating autophagy. However, GBE has demonstrated notable efficacy in alleviating the reproductive toxicity induced by DM. ConclusionOur findings highlighted that SKP2 is a key regulator of Beclin1-independent autophagy and that GBE exerts therapeutic effects by upregulating SKP2 and inhibiting Beclin1 activation, which ameliorates autophagy and reduces DM-induced testicular damage.

Deoxynivalenol induces ovarian damage and uterine changes in prepubertal and adult mice

Deoxynivalenol (DON) is associated with reproductive toxicity in animals. The frequent contamination of cereal-based foods with DON and the high intake of these by children raises particular concern about the susceptibility of this subpopulation to adverse effects from this mycotoxin. However, age-related differences in the in vivo reproductive toxicity of DON have not been evaluated. Therefore, the effects of DON on serum follicle-stimulating hormone (FSH) levels, histology, and inflammatory and oxidative stress responses in the ovaries and uteruses of prepubertal and adult mice were investigated. Twenty female prepubertal Swiss mice (21 days old) and 20 young adult mice (65 days old) were fed a control diet or a diet containing 10 mg of DON/kg of feed for 15 days (prepubertal mice) and 28 days (adult mice). In the ovaries, DON induced an increase in the lesional score in both age groups. Ingestion of DON decreased FSH levels in prepubertal females, whereas an increase was observed in adult mice. In prepubertal mice, a reduction in the number of macrophages and increased levels of TNF-α were observed in the ovaries of the DON group, while in adult animals, an increase in the number of macrophages and higher levels of TNF-α were noted. The prepubertal animals showed edema in the uterine tissue and increased thickness of the uterine wall and endometrium. Exposure to DON led to an increase in type I collagen in the uteruses of adult mice, while in prepubertal mice, a decrease in type III collagen was observed. DON exposure also resulted in a decrease in FRAP levels and an increase in ABTS and lipid peroxidation in the uteruses of prepubertal mice. Taken together, the results indicate that the effects of DON on reproductive organs are age-specific, with toxicity established as early as the prepubertal period.

Exploring the ameliorative potential of rutin against High-Sucrose Diet-induced oxidative stress and reproductive toxicity in Drosophila melanogaster

Sucrose is a vital ingredient in numerous food items consumed regularly. However, exposure to excessive sucrose for a prolonged period can promote health issues. The reproductive system has a delicate physiology that can be targeted by various chemical stressors, including sucrose. Hence, the present in vivo study aims to unveil the impacts of the High-Sucrose Diet (HSD) on the reproductive fitness of Drosophila melanogaster. In addition, the present work has also assessed the protective potential of a bioactive compound, rutin, against it. Here, 1st instar larvae were exposed to HSD (30%) alone and in combination with rutin (100-300µM) till their adult stage. HSD disturbed sex comb morphology in adult males, while fecundity and hatchability of eggs in females. Moreover, HSD triggered gonadal ROS production, oxidative stress, and modulated endogenous antioxidants such as SOD, catalase, and glutathione in both sexes. Nuclear fragmentation and tissue injuries, along with protein and lipid oxidation, were also apparent. Elevated levels of cytosolic Iron suggested an active Fenton reaction in adults. Further, HSD modulated the activities of reproductive and metabolic mediators, including vitellogenin, malate dehydrogenase, glucose-6-phosphate dehydrogenase, and angiotensin-converting enzymes that are critical to overall reproductive fitness. Interestingly, co-treatment with rutin, mainly at 200µM, mitigated these adverse effects and restored reproductive fitness. The protective potential of rutin might be attributed to its ability to normalize redox homeostasis, reduce oxidative stress, and optimize critical enzymes involved in reproductive physiology. These findings suggest that rutin has potential therapeutic implications to counteract the reproductive hazards induced by HSD.