Perspectives of Nanoparticles in Male Infertility: Evidence for Induced Abnormalities in Sperm Production

Iftikhar, Mehwish; Noureen, Aasma; Uzair, Muhammad; Jabeen, Farhat; Abdel-Daim, Mohamed M.; Cappello, Tiziana

doi:10.3390/ijerph18041758

Cited by 45 publications

(27 citation statements)

References 137 publications

(121 reference statements)

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“…An increasing number of studies is focusing on the male reproductive toxicity of SNPs [ 6 , 13 , 15 , 29 , 30 ]. SNPs can penetrate the mouse blood–testis barrier and exert their toxic actions.…”

Section: Discussionmentioning

confidence: 99%

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Activation of Autophagy by Low-Dose Silica Nanoparticles Enhances Testosterone Secretion in Leydig Cells

Zhang

Grunberger

et al. 2022

IJMS

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Silica nanoparticles (SNPs) can cause abnormal spermatogenesis in male reproductive toxicity. However, the toxicity and toxicological mechanisms of SNPs in testosterone synthesis and secretion in Leydig cells are not well known. Therefore, this study aimed to determine the effect and molecular mechanism of low doses of SNPs in testosterone production in Leydig cells. For this, mouse primary Leydig cells (PLCs) were exposed to 100 nm Stöber nonporous spherical SNPs. We observed significant accumulation of SNPs in the cytoplasm of PLCs via transmission electron microscopy (TEM). CCK-8 and flow cytometry assays confirmed that low doses (50 and 100 μg/mL) of SNPs had no significant effect on cell viability and apoptosis, whereas high doses (more than 200 μg/mL) decreased cell viability and increased cell apoptosis in PLCs. Monodansylcadaverine (MDC) staining showed that SNPs caused the significant accumulation of autophagosomes in the cytoplasm of PLCs. SNPs activated autophagy by upregulating microtubule-associated protein light chain 3 (LC3-II) and BCL-2-interacting protein (BECLIN-1) levels, in addition to downregulating sequestosome 1 (SQSTM1/P62) level at low doses. In addition, low doses of SNPs enhanced testosterone secretion and increased steroidogenic acute regulatory protein (StAR) expression. SNPs combined with rapamycin (RAP), an autophagy activator, enhanced testosterone production and increased StAR expression, whereas SNPs combined with 3-methyladenine (3-MA) and chloroquine (CQ), autophagy inhibitors, had an opposite effect. Furthermore, BECLIN-1 depletion inhibited testosterone production and StAR expression. Altogether, our results demonstrate that low doses of SNPs enhanced testosterone secretion via the activation of autophagy in PLCs.

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Section: Discussionmentioning

confidence: 99%

“…In males, testes are vulnerable and sensitive to exposure to numerous nanoparticles, such as carbon black nanoparticles (CBNPs) and SNPs [ 6 , 7 , 8 , 9 , 10 ]. SNPs have been observed to pass through the blood–testis barrier and distribute inside testicular tissue [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Activation of Autophagy by Low-Dose Silica Nanoparticles Enhances Testosterone Secretion in Leydig Cells

Zhang

Grunberger

et al. 2022

IJMS

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“…Findings of this study confirmed previous studies' findings, which showed that exposure to NPs caused toxic effects and the generation of infection in testes tissue. These, in part, are due to the accumulation of these particles and by the conversion of CuNPs by hydrogen into cupric ions, which are very toxic to tissues [ 30 – 32 ].…”

Section: Resultsmentioning

confidence: 99%

Histopathological and Biochemical Comparative Study of Copper Oxide Nanoparticles and Copper Sulphate Toxicity in Male Albino Mice Reproductive System

AL-Musawi

Al-Shmgani

Al-Bairuty

2022

International Journal of Biomaterials

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Copper (Cu) is an essential trace element for the efficient functioning of living organisms. Cu can enter the body in different ways, and when it surpasses the range of biological tolerance, it can have negative consequences. The use of different nanoparticles, especially metal oxide nanoparticles, is increasingly being expanded in the fields of industry and biomedical materials. However, the impact of these nanoparticles on human health is still not completely elucidated. This comparative study was conducted to evaluate the impacts of copper oxide nanoparticles (CuO NPs) and copper sulphate (CuSO4 0.5 (H2O)) on infertility and reproductive function in male albino mice BALB/c. Body weight, the weight of male reproductive organs, malondialdehyde (MDA) level, caspase-3 level, and the presence of Ki67 and CD68, as detected using the amino-histochemistry technique, were investigated. Animals were treated with 25 and 35 mg/kg of CuO NPs and CuSO4 0.5 (H2O) by oral gavage for 14 days. The control group was given distilled water by oral gavage. Body weight significantly decreased at the end of experiments in both treated groups in a concentration- and time-dependent manner compared with the control group. Weights of testes and epididymis (head and tail), as well as the weight of the seminal vesicle, showed a significant decrease compared with the control. However, the average weights of the seminal vesicle and prostate significantly increased. Caspase-3 and MDA levels increased in the CuO NP and CuSO4 0.5 (H2O) groups compared with the control group, and there was a significant difference between the two concentrations used. Immunohistochemical results detected a significant decrease in Ki67 protein in the treatment groups compared with the control. However, increase in CD68 protein was found in groups treated with CuO NPs and CuSO4 0.5 (H2O) compared with the control group. Overall, this in vivo comparative study of CuO NPs and CuSO4 0.5 (H2O) showed that oral intake of copper NPs at 25 and 23 mg/kg was safer to the mice reproductive system than CuSO4 0.5 (H2O) at the same dose. CuSO4 0.5 (H2O) significantly influenced the histopathological and toxicological alteration responses.

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“…At the cellular level, NPs affect the quality and quantity of sperm and Leydig cells. At the organ level, NPs make histological alterations, change the structure of the reproductive organ, cause damage to testes, decrease epididymis and testes weight, empty seminiferous tubules, and alter seminiferous tubules diameter and morphology ( Iftikhar et al, 2021 ). Besides male and female reproductive system and transplacental barrier, they are also involved in altering fetal growth and organ formation by causing teratogenic effects (reducing bone, sternum, toes, and fingers formation) and mortality.…”

Section: Advancements In Predicting the Nanotoxic Effects On Biological Barriersmentioning

confidence: 99%

Novel Methods and Approaches for Safety Evaluation of Nanoparticle Formulations: A Focus Towards In Vitro Models and Adverse Outcome Pathways

et al. 2021

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Nanotoxicology is an emerging field employed in the assessment of unintentional hazardous effects produced by nanoparticles (NPs) impacting human health and the environment. The nanotoxicity affects the range between induction of cellular stress and cytotoxicity. The reasons so far reported for these toxicological effects are due to their variable sizes with high surface areas, shape, charge, and physicochemical properties, which upon interaction with the biological components may influence their functioning and result in adverse outcomes (AO). Thus, understanding the risk produced by these materials now is an important safety concern for the development of nanotechnology and nanomedicine. Since the time nanotoxicology has evolved, the methods employed have been majorly relied on in vitro cell-based evaluations, while these simple methods may not predict the complexity involved in preclinical and clinical conditions concerning pharmacokinetics, organ toxicity, and toxicities evidenced through multiple cellular levels. The safety profiles of nanoscale nanomaterials and nanoformulations in the delivery of drugs and therapeutic applications are of considerable concern. In addition, the safety assessment for new nanomedicine formulas lacks regulatory standards. Though the in vivo studies are greatly needed, the end parameters used for risk assessment are not predicting the possible toxic effects produced by various nanoformulations. On the other side, due to increased restrictions on animal usage and demand for the need for high-throughput assays, there is a need for developing and exploring novel methods to evaluate NPs safety concerns. The progress made in molecular biology and the availability of several modern techniques may offer novel and innovative methods to evaluate the toxicological behavior of different NPs by using single cells, cell population, and whole organisms. This review highlights the recent novel methods developed for the evaluation of the safety impacts of NPs and attempts to solve the problems that come with risk assessment. The relevance of investigating adverse outcome pathways (AOPs) in nanotoxicology has been stressed in particular.

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Perspectives of Nanoparticles in Male Infertility: Evidence for Induced Abnormalities in Sperm Production

Cited by 45 publications

References 137 publications

Activation of Autophagy by Low-Dose Silica Nanoparticles Enhances Testosterone Secretion in Leydig Cells

Activation of Autophagy by Low-Dose Silica Nanoparticles Enhances Testosterone Secretion in Leydig Cells

Histopathological and Biochemical Comparative Study of Copper Oxide Nanoparticles and Copper Sulphate Toxicity in Male Albino Mice Reproductive System

Novel Methods and Approaches for Safety Evaluation of Nanoparticle Formulations: A Focus Towards In Vitro Models and Adverse Outcome Pathways

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