Selenium mitigates methotrexate-induced testicular injury: Insights from male NMRI mice model.

BACKGROUND AND AIM: Chemotherapy, particularly with methotrexate (MTX), often elicits testicular toxicity, leading to impaired spermatogenesis and hormone imbalances. This study aimed to investigate the potential protective effects of selenium (Se) against MTX-induced testicular injury. MATERIALS AND METHODS: Male mice were divided into control, MTX, Se, and MTX + Se groups. Histopathological examination involved the preparation of testicular tissue sections using the Johnsen's tubular biopsy score (JTBS) for spermatogenesis evaluation. Biochemical tests included the assessment of testosterone, malondialdehyde (MDA), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to analyze the expression of caspase 3 (casp3), tumor protein 53 (p53), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) genes. Statistical analysis was performed using ANOVA and Tukey's tests (p < .05). RESULTS: Histopathological analysis revealed significant testicular damage in the MTX group, with decreased spermatogenesis and Leydig cell count, while Se administration mitigated these effects, preserving the structural integrity of the reproductive epithelium. Biochemical analysis demonstrated that MTX led to elevated malondialdehyde (MDA) levels and reduced testosterone, LH, and FSH levels, suggesting oxidative stress and Leydig cell dysfunction. Gene expression analysis indicated that MTX upregulated proapoptotic genes (casp3, p53, and bax) while downregulating the antiapoptotic Bcl2 gene. In contrast, Se treatment reversed these trends, highlighting its potential antiapoptotic properties. CONCLUSION: Our findings underscore the potential of Se as a therapeutic agent to mitigate the reproductive toxicity associated with MTX-induced testicular injury. Se exerts protective effects by regulating oxidative stress, preserving hormone balance, and modulating apoptotic pathways. These results suggest that Se supplementation could be a promising strategy to alleviate chemotherapy-induced testicular damage and preserve male fertility.

Effect of Cerium Oxide Nanoparticles on the Expression of Developmental and Apoptosis Genes of Testicular Tissue in 6-Day-Old NMRI Mice Fetuses.

Cerium oxide (CeO2) has potential applications in medicine and various consumer products. This study investigated the effect of CeO2 on the expression of genes associated with apoptosis and testicular development in mouse embryos. The experimental groups of pregnant mice were injected intraperitoneally with CeO2 at a concentration of 10 mg/kg on days 7 and 14 of pregnancy. Six days after birth, the testicles of neonatal male mice were collected for mRNA expression determination using real-time PCR, protein expression analysis by immunohistochemistry, and apoptotic cell population determination using the TUNEL assay. The results showed that the mRNA expression of the Bax, Caspase-3, and Gsk3-ß genes, unlike the Bcl2 gene, decreased significantly in the experimental group compared to the control group. The expression ratio of Bax/Bcl2 in the experimental group was lower than in the control group. A similar trend was observed in the population of apoptotic cells. In the experimental group, the expression levels of, Gata4, Sox8, and Rad54 at both the mRNA and protein levels increased significantly compared to the control group. Based on the results of this study, CeO2 at a concentration of 10 mg/kg, in addition to producing anti-apoptotic effects on the testicular cells of neonatal mice, can increase the expression of genes involved in testicular development and performance. The current experimental study proved the protective effects of 10 mg/kg CeO2 in developmental and apoptosis genes of testicular tissue in 6-day-old NMRI mice fetuses; however, more experiments are required to evaluate the possible side effects and interactions.

The effect of different concentrations of cerium oxide during pregnancy on ovarian follicle development in neonatal mice.

OBJECTIVES: Cerium is a member of the rare metals group and widely used in drug delivery, gene therapy, molecular imaging and medicine. In this study, we investigated the effect of different doses of Cerium (IV) oxide (CeO2 ) during pregnancy on neonatal mice ovaries, as well as its effect on blood biochemical parameters. METHODS: Thirty pregnant NMRI mice were divided into five groups: Control and 4 groups treated with CeO2 (10, 25, 80, 250 mg/kg.bw i.p) at the GD7 and GD14. The ovarian histological of neonatal (2 and 6 day-olds), as well as blood serum of neonates at 15-dpp were analyzed. RESULTS: Count of ovarian primordial follicles in neonates at 2 dpp showed a significant decrease in the groups treated with 80 and 250 mg/kg.bw doses of CeO2 . There was also a significant decrease in ovarian primordial and primary follicles in neonates at 6-dpp at 250 mg/kg.bw doses of CeO2 in the control (P < 0.05). There was no significant difference in serum levels of malondialdehyde and total antioxidant capacity between the experimental and control groups. CONCLUSIONS: Our results suggest that the effects of CeO2 on the ovarian tissue of neonatal mice during pregnancy may be dose-dependent.

A Stereological Study of the Toxic Effects of Cerium Oxide during Pregnancy on Kidney Tissues in Neonatal NMRI Mice.

BACKGROUND: Both antioxidant and prooxidant activities have been previously reported for cerium oxide (CeO2). The aim of this study was to investigate the effects of CeO2 at different doses on changes in kidney tissues and markers in neonatal mice. METHODS: We randomly divided 30 pregnant NMRI mice into five groups (n = 6 per group)-a control group and four groups treated with intraperitoneal (i.p.) administration of different doses of CeO2 (10, 25, 80, or 250 mg/kg body weight (bw)) on gestation days (GD) 7 and GD14. At the end of the treatment period, we analyzed the kidney tissues and serum samples. The levels of two serum redox markers, malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP), were determined. Data were analyzed using one-way ANOVA and Tukey's test, and a P value of <0.05 was considered significant. RESULTS: The mean total volumes of the renal corpuscle, glomeruli, and Bowman's capsule membranes significantly increased, and there was a significant decrease in the mean total volume of Bowman's space in the high-dose CeO2 group compared to that in the control group. No statistically significant differences existed in the serum levels of MDA and FRAP in the treated and control groups. CONCLUSION: Our results suggest that high doses of CeO2 impair fetal renal development in pregnant mice, which results in kidney damage. Therefore, CeO2 administration during pregnancy could have dose-dependent adverse effects on the developing kidneys in neonates.

The Effect of Cerium Oxide During Pregnancy on the Development of the Testicular Tissue of Newborn NMRI Mice.

Cerium(IV) oxide is widely used as a catalyst in all aspects of human life and human beings are exposed to these materials. The purpose of this experimental study was to investigate the effect of CeO2 during pregnancy on alterations in the testis tissue and blood biochemical parameters in newborn mice. Pregnant NMRI mice were divided randomly into five groups (n = 6 for each group) including one control group and 4 treatment groups. Injection of CeO2 solution was administered intraperitoneally at the doses of 10, 25, 80, and 250 mg/kg.bw, respectively, on GD 7 and GD 14. At the end of treatment period, the testicular histological and biochemical parameters of 2- and 6-day-old newborns were analyzed, as well as the biochemical parameters in serum samples of 15-day-old newborns. The number of spermatogonia, Sertoli, and Leydig cells in the testis of the 2-day-old newborn and spermatogonia and Leydig cells in the testis of the 6-day-old newborns in the 250 mg/kg.bw CeO2 treatment group was significantly reduced compared with the control group (P < 0.05). Testis MDA of the 2- and 6-day-old newborns in the treated group receiving 250 mg/kg.bw of CeO2 was significantly higher than the control group (P < 0.001). There was no significant difference between serum MDA and TAC levels between the treated groups with different doses of CeO2 compared with the control group. Therefore, CeO2 given to dams during pregnancy may affect the testicular tissue and blood biochemical parameters in neonates and may be dose-dependent.