Zinc oxide nanoparticles improve testicular steroidogenesis machinery dysfunction in benzo[α]pyrene-challenged rats.
Ontology highlight
ABSTRACT:
SUBMITTER: Daoud NM
PROVIDER: S-EPMC8175368 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundBenzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon (PAH), is a ubiquitous environmental pollutant that is currently suspected of being an endocrine disruptor. The testis is an important target for PAHs, yet insufficient attention has been paid to their effects on steroidogenesis in Leydig cells.ObjectiveWe hypothesized that long-term exposure to low concentrations of B[a]P might disrupt testosterone production in Leydig cells via an alteration of steroidogenic proteins.ResultsOral exposure to B[a]P reduced serum and intratesticular fluid testosterone levels in rats. However, we did not observe serious testicular atrophy or azoospermia, although spermatogonial apoptosis was significantly increased. Compared with control cells, Leydig cells primed with B[a]P in vivo produced less testosterone in response to human chorionic gonadotropin (hCG) or dibutyl cyclic adenosine monophosphate in vitro. Of note, the reduction of testosterone levels was accompanied by decreased expression of steroidogenic acute regulatory protein (StAR) and 3?-hydroxysteroid dehydrogenase (3?-HSD), as well as increased levels of cytochrome P450 side chain cleavage (P450scc), in Leydig cells. The up-regulation of P450scc expression after exposure to B[a]P appears to be associated with a compensatory mechanism for producing the maximum amount of pregnenolone with the minimum amount of transported cholesterol by StAR; the down-regulation of 3?-HSD may occur because B[a]P can negatively target 3?-HSD, which is required for testosterone production.ConclusionsB[a]P exposure can decrease epididymal sperm quality, possibly by disturbing testosterone levels, and StAR may be a major steroidogenic protein that is targeted by B[a]P or other PAHs.
| S-EPMC3226498 | biostudies-literature
Project description:The present work is aimed to assess the protective influence of zinc oxide resveratrol nanoparticles against oxidative stress-associated testicular dysfunction. The number of 50 male albino rats were randomly separated into five groups (n = 10): Group I, control: rats gavage distilled water orally; Group II, Levofloxacin: rats that administered Levofloxacin (LFX) softened in distilled water at a dosage of 40 mg/kg-1 BW orally every other day; Group III, Zn-RSV: rats administered with Zn-RSV (zinc oxide resveratrol in distilled water at a dose 20 mg/kg-1 BW orally every other day; Group IV, (LFX + Zn-RSV): rats that were administered with Levofloxacin along with Zn-RSV nPs; Group V, Levofloxacin + Zn: rats were administered with Levofloxacin and Zno at a dose of 20 mg/kg-1 BW orally every other day as mentioned before. This study lasted for 2 months. Sera were collected to assess luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone values. Testicular tissues were utilized to evaluate levels of superoxide dismutase (SOD), nitric oxide (NO), malondialdehyde (MDA), and catalase (CAT). Semen samples were utilized to measure their quality (motility, concentration, and vitality). Histopathological and immune histochemical techniques investigated the morphological changes in the testis. Rats treated with Levofloxacin showed significantly lower levels of serum LH, testosterone, FSH, testicular enzymatic NO, catalase, SOD, BAX, and BCL-2 immune reactivity and sperm quality but significantly greater testicular malondialdehyde and caspase-3 immuno-reactivity Compared to both control and zinc oxide resveratrol treatment. Zinc oxide resveratrol nanoparticles ameliorated the harmful side effects of Levofloxacin. Improvements were more pronounced in the co-treatment (LFX + Zn-RSV) Zinc oxide resveratrol group than in the co-treatment (LFX + Zno) Zinc oxide group. Zinc oxide resveratrol nanoparticles could be a possible solution for levofloxacin oxidative stress-induced fertility problems.
| S-EPMC10837121 | biostudies-literature
Project description:Alcoholism and cigarette smoking are pervasive problems that have been implicated in human health. In this study, independent and combinative toxicities of alcohol and benzo(a)pyrene (BaP) were tested for reproductive toxicity in rats. Male Wistar rats were exposed to BaP (100 ?g per kg body weight) on alternative days and alcohol (2 g per kg body weight per day) daily, either individually or in combination for 60 days. Exposure to BaP or alcohol significantly decreased the fertility index and reduced the number of implantations associated with elevated pre- and post-implantation losses. The relative weights of testes, epididymis, seminal vesicles, and prostate gland were significantly decreased in BaP or alcohol administered rats. Exposure to BaP or alcohol significantly decreased daily sperm production, sperm density, percentages of motile, viable, HOS-tail swelled sperm, testicular 3?- and 17?-hydroxysteroid dehydrogenase activity levels, mRNA levels of steroidogenic acute regulatory protein, and serum testosterone levels. Further, in silico studies revealed the binding of BaP at the hydrophobic tunnel of StAR protein. Additional studies disclosed stable interactions of BaP with the amide group of ASN150 and the hydroxyl group of THR263 by forming three hydrogen bonds. Our results also showed that treatment of rats with BaP or alcohol caused a marked increase in levels of superoxide anions, hydrogen peroxide, and lipid peroxidation in testis and epididymis. Conversely, glutathione levels and activity levels of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in testis as well as epididymis decreased significantly in the experimental rats. Under the same conditions, increased fragmented DNA levels were observed in sperm. The results of the present study indicate that exposure to BaP or alcohol adversely affected the male reproductive functions, which may be, at least in part, due to androgen deficiency and/or oxidative stress-related mechanisms. Consistently, the present results also showed higher reproductive toxicity upon exposure to combinations of BaP and alcohol than upon their individual treatments. Therefore, this combination was classified as additive and synergistic responses of BaP and alcohol.
| S-EPMC6062366 | biostudies-literature
Project description:Cyclophosphamide (CP) is a cytotoxic, cell cycle, non-specific, and antiproliferative drug. This study aimed to address the toxic effects of CP on male fertility and the possible ameliorative role of hesperidin (HSP). Thirty-two adult albino rats were randomly divided into four groups, namely, the negative control, HSP, CP-treated, and CP+HSP-treated groups. The CP-treated rats showed a significant reduction in the levels of serum LH, FSH, testosterone, prolactin, testicular glutathione peroxidase (GPx), and total antioxidant capacity (TAC) with an elevation in levels of malondialdehyde (MDA), and p53, and iNOS immune expression, compared to the control group. A significant downregulation in hypothalamic KISS-1, KISS-1r, and GnRH, hypophyseal GnRHr, and testicular mRNA expression of steroidogenesis enzymes, PGC-1α, PPAR-1, IL10, and GLP-1, as well as a significant upregulation in testicular mRNA of P53 and IL1β mRNA expression, were detected in the CP-treated group in comparison to that in the control group. The administration of HSP in CP-treated rats significantly improved the levels of serum LH, FSH, testosterone, prolactin, testicular GPx, and TAC, with a reduction in levels of MDA, and p53, and iNOS immune expression compared to the CP-treated group. A significant upregulation in hypophyseal GnRHr, and testicular mRNA expression of CYP19A1 enzymes, PPAR-1, IL10, and GLP-1, as well as a significant downregulation in testicular mRNA of P53 and IL1β mRNA expression, were detected in the CP+HSP-treated group in comparison to that in the CP-treated group. In conclusion, HSP could be a potential auxiliary agent for protection from the development of male infertility.
| S-EPMC9966503 | biostudies-literature
Project description:In utero exposure of the fetus to benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon, is thought to dysregulate cardiovascular development. To investigate the effects of in utero B(a)P exposure on cardiovascular development, timed-pregnant Long Evans Hooded (LEH) rats were exposed to diluent or B(a)P (150, 300, 600 and 1200 μg/kg/BW) by oral gavage on embryonic (E) days E14 (the metamorphosing embryo stage) through E17 (the 1st fetal stage). There were no significant effects of in utero exposure to B(a)P on the number of pups born per litter or in pre-weaning growth curves. Pre-weaning profiles for B(a)P metabolite generation from cardiovascular tissue were shown to be dose-dependent and elimination of these metabolites was shown to be time-dependent in exposed offspring. Systolic blood pressure on postnatal day P53 in the middle and high exposure groups of offspring were significantly elevated as compared to controls. Microarray and quantitative real-time PCR results were directly relevant to a biological process pathway in animal models for "regulation of blood pressure". Microarray and quantitative real-time PCR analysis revealed upregulation of mRNA expression for angiotensin (AngII), angiotensinogen (AGT) and endothelial nitric oxide synthase (eNOS) in exposed offspring. Biological network analysis and gene set enrichment analysis subsequently identified potential signaling mechanisms and molecular pathways that might explain the elevated systolic blood pressures observed in B(a)P-exposed offspring. Our findings suggest that in utero exposure to B(a)P predispose offspring to functional deficits in cardiovascular development that may contribute to cardiovascular dysfunction in later life.
| S-EPMC3575114 | biostudies-literature
Project description:Leydig cells represent the steroidogenic lineage of mammalian testis, which produces testosterone. Genetic evidence indicates the requirement of Notch signaling in maintaining a balance between differentiated Leydig cells and their progenitors during fetal development. In primary Leydig cells, Notch1 expression decreases with testicular development, while the expression of its ligand, Jagged1, remains relatively unchanged, suggesting that the roles of Jagged1 extend beyond Notch signaling. In addition, Jagged1 is known to be processed into its intracellular domain, which then translocate to the nucleus. In this study, we investigated the effect of Jagged1 intracellular domain (JICD) on steroidogenesis in Leydig cells. The independent overexpression of JICD in MA-10 Leydig cells was found to inhibit the activity of cAMP-induced Nur77 promoter. In addition, JICD suppressed Nur77 transactivation of the promoter of steroidogenic genes such as P450scc, P450c17, StAR, and 3β-HSD. Further, adenovirus-mediated overexpression of JICD in primary Leydig cells repressed the expression of steroidogenic genes, consequently lowering testosterone production. These results collectively suggest that steroidogenesis in testicular Leydig cells, which is regulated by LH/cAMP signaling, is fine-tuned by Jagged1 during testis development.
| S-EPMC7773251 | biostudies-literature
Project description:The objective of this study was to investigate effects of zinc glycinate (ZnGly) supplementation reducing zinc oxide (ZnO) in feeds on intestinal health and growth of nursery pigs challenged with F18+Escherichia coli (E. coli). In total, 72 nursery pigs (BW 6.5 ± 0.5 kg) were allotted in a randomized complete block design to nine treatments: (1) NC: no challenge/no supplement; (2) PC: E. coli challenge/no-supplement; (3) E. coli challenge/ZnO at 2,500 mg/kg; (4, 5, and 6) E. coli challenge/ZnGly at 400, 800, and 1,200 mg/kg; and (7, 8, and 9) E. coli challenge/ZnGly at 400 mg/kg and ZnO at 700, 1,400, and 2,357 mg/kg. Pigs were fed for 28 d based on two phases (phase 1: 14 d and phase 2: 14 d). On day 7, challenged groups were orally inoculated with F18+E. coli at 6 × 109 CFU/mL whereas NC received saline solution. The PC showed reduced ADG (P = 0.076) and G:F (P = 0.055) during phase 1 and increased fecal score (P < 0.05) during the first week of postchallenge when compared with NC, whereas supplementation of ZnGly from 0 to 1,200 mg/kg linearly increased (P = 0.092) G:F and decreased (P < 0.05) the fecal score of the pigs challenged with F18+E. coli. Supplementation of ZnGly from 0 to 1,200 mg/kg had quadratic effects on TNF-α (P = 0.065; minimum 1.13 pg/mg at 850 mg/kg ZnGly), IL-8 (P = 0.093; minimum 0.53 ng/mg at 494 mg/kg), and protein carbonyl (P = 0.054; minimum 2.30 pg/mg at 675 mg/kg) and linearly increased mRNA expressions of ZIP4 (P = 0.057) and ZnT5 (P = 0.075) in the jejunum of the pigs. Supplementation of ZnGly from 0 to 1,200 mg/kg linearly increased (P < 0.05) the relative abundance of Actinobacteria and had quadratic effects on Cyanobacteria (minimum 0.67% at 625 mg/kg ZnO) and Proteobacteria (maximum 45.6 g/d at 735 mg/kg) at the phylum level, with linearly decreased (P < 0.05) Enterobacteriaceae at the family level in the jejunal mucosa-associated microbiota of the pigs. There was no difference in growth performance during the overall period, although pigs fed with ZnO at 2,500 mg/kg had greater (P < 0.05) ADG than pigs fed with ZnGly at 400 mg/kg during the first week of the post challenge period. In conclusion, ZnGly could be an alternative to the pharmaceutical use of ZnO without negatively affecting the growth of nursery pigs by enhancing intestinal Zn absorption, reducing intestinal inflammation and oxidative stress, and providing positive changes in jejunal mucosa-associated microbiota.
| S-EPMC10195191 | biostudies-literature
Project description:Multiple sclerosis (MS) is an autoimmune disease that usually occurs during the reproductive years in both sexes. Many male patients with MS show lower blood testosterone levels, which was also observed in male rats during experimental autoimmune encephalomyelitis (EAE), an animal model of MS. To better understand the causes of decreased testosterone production during EAE, we investigated the expression status of genes and proteins associated with steroidogenesis in the testes. No changes in the number of interstitial cells were observed in EAE animals, but the expression of the insulin-like 3 gene was reduced at the peak of the disease, implying that the Leydig cell functional capacity was affected. Consistent with this finding, the expression of most steroidogenic enzyme genes and proteins was reduced during EAE, including StAR, CYP11A1, CYP17A1 and HSD3B. No signs of testicular inflammation were observed. Recovery of steroidogenesis was observed after injection of hCG, the placental gonadotropin, or buserelin acetate, a gonadotropin-releasing hormone analogue, at the peak of EAE. Together, our results are consistent with the hypothesis that impaired testicular steroidogenesis originates upstream of the testes and that low serum LH is the main cause of decreased testosterone levels during EAE.
| S-EPMC8076254 | biostudies-literature
Project description:Benzo[a]pyrene, a ubiquitous environmental pollutant, has been suggested to be capable of initiating and/or accelerating atherosclerosis. Accumulation of vascular smooth muscle cells (VSMCs) in vessel intima is a hallmark of atherosclerosis. Nitric oxide (NO) can suppress VSMCs proliferation and induce VSMCs apoptosis. NO plays a compensatory role in the vascular lesions to reduce proliferation and/or accelerate apoptosis of VSMCs. The aim of this study was to investigate whether benzo[a]pyrene can affect VSMCs growth and apoptosis induced by NO. Benzo[a]pyrene (1-30 ?mol/L) did not affect the cell number and cell cycle distribution in VSMCs under serum deprivation condition. Sodium nitroprusside (SNP), a NO donor, decreased cell viability and induced apoptosis in VSMCs. Benzo[a]pyrene significantly suppressed SNP-induced cell viability reduction and apoptosis. VSMCs cultured in conditioned medium from cells treated with benzo[a]pyrene could also prevent SNP-induced apoptosis. Benzo[a]pyrene was capable of inducing the activation of nuclear factor (NF)-?B and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in VSMCs. Both NF-?B inhibitor and p38 MAPK inhibitor significantly reversed the anti-apoptotic effect of benzo[a]pyrene on SNP-treated VSMCs. Incubation of VSMCs with benzo[a]pyrene significantly and dose-dependently increased interleukin (IL)-6 production. A neutralizing antibody to IL-6 effectively reversed the anti-apoptotic effect of benzo[a]pyrene on SNP-treated VSMCs. Taken together, these results demonstrate for the first time that benzo[a]pyrene activates IL-6 induction and protects VSMCs from NO-induced apoptosis. These findings propose a new mechanism for the atherogenic effect of benzo[a]pyrene.
| S-EPMC5439712 | biostudies-literature
Project description:Persistent and ubiquitous organic pollutants, such as the polycyclic aromatic hydrocarbon benzo[⍺]pyrene (BaP), represent a major threat to aquatic organisms and human health. Beside some well-documented adverse effects on the development and reproduction of aquatic organisms, BaP was recently shown to affect fish bone formation and skeletal development through mechanisms that remain poorly understood. In this work, several bone-related in vivo assays were used in zebrafish to evaluate the osteotoxic effects of BaP during bone development and regeneration. Exposure to BaP for 3 days induced a dose-dependent reduction of the size of the opercular bone in 6 days post-fertilization (dpf) larvae, and affected osteoblast maturation as observed by the expression of the mature marker, osteocalcin. Exposure to BaP for 27 days affected the development of the axial skeleton and increased the incidence and severity of skeletal deformities. During bone regeneration, BaP affected the mineralization of newly formed fin rays and scales, while it impaired fin ray patterning and scale shape, through mechanisms that may involve an imbalance of bone remodeling. Transcriptomic and gene expression analyses indicate that BaP induced the activation of xenobiotic and metabolic pathways, while negatively impacting extracellular matrix formation and organization. Interestingly, BaP exposure positively regulated inflammation markers in 6 dpf larvae and increased neutrophil recruitment. A direct interaction between neutrophils and bone extracellular matrix or bone forming cells was observed in vivo, suggesting a role for neutrophils in the mechanisms underlying BaP osteotoxicity. Our work provides novel data on the cellular and molecular players involved in BaP osteotoxicity and brings new insights into a possible role for neutrophils in inflammatory bone reduction.
2024-04-29 | GSE174529 | GEO