The aim of this study was to investigate the effects of metformin supplementation on metabolic dysfunction, testicular antioxidant capacity, apoptosis, inflammation and spermatogenesis in male mice with high-fat and high-cholesterol diet-induced obesity. Forty male C57BL/6 mice were fed a normal diet (NC group, n = 10) or a high-fat and high-cholesterol diet (HFC group, n = 30) for 24 weeks, and mice randomly chosen from the HFC group were later treated with metformin for the final 8 weeks of HFC feeding (HFC + Met group, n = 15). Compared with the HFC group, the obese mice supplemented with metformin exhibited improved blood cholesterol, glucose and insulin resistance. The HFC group diminishes in the sperm motility and normal sperm morphology, while the poorer maturity of testicular spermatogenesis was improved by metformin treatment. The HFC group exhibited a higher estradiol level and a lower 17β-HSD protein expression. Further analyses showed that metformin treatment increased the activities of superoxide dismutase, catalase and glutathione peroxidase and reduced lipid peroxidation. Nevertheless, both the HFC and HFC + Met groups exhibited increased expressions of apoptosis and inflammation proteins in the testis. Metformin treatment ameliorated obesity-induced poor testicular spermatogenesis and semen quality through increasing the testosterone level and antioxidant capacity.

Iron deficiency is the most common micronutrient deficiency in the world. Previous studies have shown that iron deficiency increases oxidative stress and decreases antioxidant enzymes, and studies of male infertility indicated that oxidative stress may affect male reproductive functions. The aim of this study was to investigate the effects of iron supplementation on spermatogenesis and testicular functions in iron-deficient rats. Three-week-old male Sprague Dawley (SD) rats were randomly divided into two groups: an iron-adequate control (AI group, 35 ppm FeSO₄) and an iron-deficient group (ID group, <5 ppm FeSO₄). After three weeks, the iron-deficient group was divided into an original iron-deficient group and five iron-supplemented groups, the latter fed diets containing different doses of FeSO₄ (6, 12, 18, 24, and 35 ppm). After five weeks, blood and testis tissue were analyzed. We presented as median (interquartile range, IQR) for continuous measurements and compared their differences using the Kruskal–Wallis test followed by the Mann–Whitney U test among groups. The results showed that as compared with the AI group, the ID group had significantly lower serum testosterone and poorer spermatogenesis (The medians (QR) were 187.4 (185.6–190.8) of AI group vs. 87.5 (85.7–90.4) of ID group in serum testosterone, p < 0.05; 9.3 (8.8–10.6) of AI group vs. 4.9 (3.4–5.4) of ID group in mean testicular biopsy score (MTBS], p < 0.05); iron supplementation reversed the impairment of testis tissue. In the testosterone biosynthesis pathway, iron supplementation improved the lowered protein expressions of hydroxysteroid dehydrogenases caused by iron deficiency. Additionally, decreased activities of glutathione peroxidase and catalase, and increased cleaved-caspase 8 and caspase 3 expression, were found in the iron-deficient rats. The iron-supplemented rats that received > 12 ppm FeSO₄ exhibited improvements in antioxidant levels. In conclusion, iron supplementation can abrogate testis dysfunction due to iron deficiency through regulation of the testicular antioxidant capacity.

Increasing reports on the significance of dietary patterns in reproduction have arisen from both animal and human studies, suggesting an interactive association between nutrition and male fertility. The aim of this study was to investigate the effects of curcumin supplementation on low-carbohydrate-diet-induced metabolic dysfunction, testicular antioxidant capacity, apoptosis, inflammation and spermatogenesis in male mice. Male C57BL/6 mice were fed a normal diet (AIN-93M group, n = 12) and a low-carbohydrate diet for 12 weeks (LC group, fed with low-carbohydrate diet, n = 48), and mice randomly chosen from the LC group were later fed their original diet (LC group, n = 12). This diet was changed to AIN-93M feed (LC/AIN-93M group, n = 12), a ketogenic diet (LC/KD group, n = 12), or a ketogenic diet treated with curcumin supplementation for the final 6 weeks (LC/KDCu group, n = 12). A poor sperm morphology and mean testicular biopsy score (MTBS) were observed in the LC and LC/KD groups, but they were eliminated by the normal diet or ketogenic diet with curcumin. The LC group exhibited a lower testicular testosterone level and a lower 17β-HSD activity and protein expression. This also enhanced apoptosis protein expressions in testis tissue, including Bax/BCl₂, cleaved caspase 3, PARP and NF-κB. Meanwhile, we found a statistically significant increase in lipid peroxidation and decreased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase levels in the LC group. Our study indicated that a replacement of a normal diet or ketogenic diet supplemented with curcumin attenuated poor semen quality and reduced testosterone levels by the LC diet by reducing oxidative stress.

Hyperphosphatemia is a serious complication in chronic kidney disease (CKD) that occurs due to insufficient excretion of phosphorus during failure of renal function. Both CKD and an excessive phosphorus intake have been reported to increase oxidative stress and result in poor male fertility, but little is known about the reproductive function of the CKD under a poorly controlled phosphate intake. Eight-week-old C57BL/6 mice (n = 66) were randomly divided into four groups: a sham operation group received a chow diet as control (SC group, n = 14), CKD-induced mice received a chow diet (CKDC group, n = 16), control mice received a high phosphorus (HP) diet (SP group, n = 16), and CKD-induced mice received a HP diet (CKDP group, n = 20). CKD was induced by performing a 5/6 nephrectomy. The chow diet contained 0.6% phosphorus, while the HP diet contained 2% phosphorus. Impaired testicular function and semen quality found in the CKD model may result from increased oxidative stress, causing apoptosis and inflammation. The HP diet aggravated the negative effects of testicular damage in the CKD-induced mice.

Our study was designed to investigate the Lactiplantibacillus plantarum 1008 (LP1008) on testicular antioxidant capacity, spermatogenesis, apoptosis, autophagy, and metabolic function in male mice with high-fat-diet-induced obesity. A total of thirty-six male C57BL/6 mice were fed a normal diet (denoted as the NC group) or a high-fat control diet (denoted as the HFC group) for 16 weeks, then half of the HFC group was randomly chosen and subsequently fed with LP1008 for the final 8 weeks (high-fat diet + LP1008; denoted as the HFP group). The HFP group expressed improved blood cholesterol, insulin resistance, hepatic function, and lipopolysaccharide (LPS) levels compared to the HFC group. Meanwhile, the HFC group displayed decreased testicular testosterone levels, sperm quality, and 17β-HSD protein expression, which were rescued after LP1008 treatment. Moreover, the HFC group had lower superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) enzyme activities. After LP1008 treatment, enhanced antioxidative activities and decreased lipid peroxidation were observed. The HFC group also exhibited aggravated apoptosis, inflammation, and autophagy proteins in the testis, which were ameliorated by LP1008 supplementation. Furthermore, the gut microbiota analysis results revealed that the Firmicutes/Bacteroidetes ratio was significantly elevated in the HFC and HFP groups compared to the NC group and that LP1008 treatment diminished Ruminococcaceae and enhanced Bifidobacteriaceae diversity. In summary, LP1008 treatment strengthened antioxidative enzyme levels and regulated microbiota-ameliorated HFC-induced oxidative stress, apoptosis, inflammation, and autophagy, and thus improved testicular function and semen quality.

The aim of the study was to examine the potential effects of coenzyme Q10 (CoQ10) on reproductive function in a chronic kidney disease (CKD) mouse model. Nine-week-old mice were randomly assigned to two groups: sham surgery (n = 18) and CKD surgery (n = 18). After surgery, the study groups received CoQ10 (10 mg/kg body weight dissolved in corn oil by oral gavage) or corn oil as a vehicle daily for 8 weeks. The groups that underwent 5/6 nephrectomy developed significant elevations of serum BUN and creatinine levels. The CoQ10 treatment significantly increased the serum and testicular CoQ10 levels and alleviated the poor semen quality from incomplete spermatogenesis. The testosterone concentration, in addition to the protein expression of enzymes related to testosterone biosynthesis, was also elevated, and the CKD-induced decrease in antioxidant activity in the testes was significantly ameliorated. The results suggest that CoQ10 could act against CKD-induced testicular dysfunction through improvements in the sperm function, testicular morphology, testosterone levels and related biosynthesis pathways, in addition to antioxidant activity.