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Background: Numerous studies have confirmed the therapeutic efficacy of bone marrow-derived mesenchymal stem cells (BM-MSCs) in addressing neurologic disorders. To date, several preconditioning strategies have been designed to improve the therapeutic potential of these stem cells. This study was designed to evaluate the preconditioning effect of dimethyl fumarate (DMF) on the expression of main trophic factors in human BM-MSCs. Materials and Methods: Initially, the identity of stem cells was confirmed through the evaluation of surface markers and their capacity for osteogenic and adipogenic differentiation using flow cytometry and differentiation assay, respectively. Subsequently, stem cells were subjected to different concentrations of DMF for 72 hours and their viability was defined by MTT assay. Following 72-hour preconditioning period with 10 µM DMF, gene expression was assessed by quantitative RT-PCR. Results: Our findings demonstrated that the isolated stem cells expressed cardinal MSC surface markers and exhibited osteogenic and adipogenic differentiation potential. MTT results confirmed that 10 µM DMF was an optimal dose for maintaining cell viability. Preconditioning of stem cells with DMF significantly upregulated the expression of BDNF, NGF, and NT-3. Despite a slight increase in transcript level of GDNF and VEGF after DMF preconditioning, this difference was not statistically significant. Conclusions: Our findings suggest that DMF preconditioning can enhance the expression of major neurotrophic factors in human BM-MSCs. Given the curative potential of both BM-MSCs and DMF in various neurological disease models and preconditioning outcomes, their combined use may synergistically enhance their neuroprotective properties.

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Exposure to heavy metals not only impacts on fertility in males, it may also affect the offspring. The aim of the present study was to examine the toxic effects of lead acetate on fertility in male mice and their offspring, and the potential effect of quercetin on mitigating the likely effects. Experimental mice were randomly divided into three groups and administered with (i) distilled water (control); (ii) lead acetate (150 mg/kg BW/day); (iii) lead acetate (150 mg/kg BW/day) with quercetin (75 mg/kg BW/day). Lead acetate administration in male mice adversely affected their fertility through changes in sperm motility, viability, morphology, maturity, membrane integrity, and intracellular reactive oxygen species (P <  0.05). Similar findings were observed in the offspring of the lead-treated male mice. Early embryonic development and implantation rate were also adversely influenced in both the sires and offspring when male mice were treated with lead acetate (P <  0.05). The data demonstrated that down-regulation of Cks2 (CDC28 protein kinase regulatory subunit-2) in sperm had an association with early embryonic development in lead acetate treated group. In conclusion, lead acetate administration adversely impacted on the fertility of the male mice and their male offspring fertility; on the other hand, paternal quercetin co-administration somewhat ameliorated the adverse effects of lead on male mice and their offspring.

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Exposure to environmental pollutants tightly impacts on the male fertility. In the present study, we examined the toxic effects of lead acetate (Pb) on testicular structure and the possible effect of quercetin on mitigating these effects. The apoptotic changes in the testes were also studied by the TUNEL assay and changes in apoptosis-related gene (Bax, Bcl-2, and caspase-3) expression. Twenty-one male mice were randomly divided into 3 groups of control, Pb, and lead acetate + quercetin. Testicular weight, both absolute and relative, was higher in Pb-exposed mice in comparison with the control and Pb-quercetin groups. The increase in size of testis was related to the lumen and connective tissue in this group. Lead acetate induced different patterns in testicular cell number; as spermatogonia, spermatocyte, and Sertoli cells number did not affect in lead acetate exposed group, while total number of round spermatids and long spermatids significantly reduced. In addition, Bcl-2 expression was downregulated, and Bax expression was upregulated in Pb-treated group in comparison with the control and Pb + quercetin groups. The TUNEL assay revealed that the number of apoptotic cells in Pb-treated group were increaed significantley in comparison to other groups. In conclusion, Pb administration adversely impacted on the cellular organization and activation of the apoptotic pathways in the testis; on the other hand, quercetin co-administration with lead partially ameliorated these adverse effects.

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Environmental pollutant effects on fertility sometime are irretrievable. The aim of this study was to investigate the effect of lead acetate and quercetin on tight (claudin 11 and occludin) and gap junctional (connexin 43) proteins and the integrity of the blood-testis barrier status. Experimental groups, including the lead acetate (Pb), quercetin (QE), lead acetate with quercetin (Pb + QE), and control mice, were treated at least one spermatogenic cycle. Gene expression of claudin 11 and occludin decreased in Pb + QE, Pb, and QE compared with the control group. Connexin 43 (Cx43) expression in the control and Pb groups was lower than in Pb + QE and QE. The immunohistochemical data were generally in line with these findings. In conclusion, the results showed that Pb exposure led to disorders in cellular interactions that affect testicular function; however, simultaneous treatment with quercetin did not alleviate these effects. Graphical Abstract.

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