Effects of Iron Supplementation on Testicular Function and Spermatogenesis of Iron-Deficient Rats

Tsao, Chih-Wei; Liao, Yuan-Ru; Chang, Ting-Chia; Liew, Yih-Fong; Liu, Chin-Yu

doi:10.3390/nu14102063

Cited by 18 publications

(6 citation statements)

References 47 publications

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“…35 Furthermore, iron is involved in nucleotide synthesis and cellular energy metabolism, and may therefore be crucial for cell proliferation and function. Finally, iron is important for biosynthesis of testosterone 36,37 which promotes muscle mass.…”

Section: Discussionmentioning

confidence: 99%

Iron deficiency is related to lower muscle mass in community‐dwelling individuals and impairs myoblast proliferation

Vinke

Gorter

Eisenga

et al. 2023

J cachexia sarcopenia muscle

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Background Loss of muscle mass is linked with impaired quality of life and an increased risk of morbidity and premature mortality. Iron is essential for cellular processes such as energy metabolism, nucleotide synthesis and numerous enzymatic reactions. As the effects of iron deficiency (ID) on muscle mass and function are largely unknown, we aimed to assess the relation between ID and muscle mass in a large population‐based cohort, and subsequently studied effects of ID on cultured skeletal myoblasts and differentiated myocytes. Methods In a population‐based cohort of 8592 adults, iron status was assessed by plasma ferritin and transferrin saturation, and muscle mass was estimated using 24‐h urinary creatinine excretion rate (CER). The relationships of ferritin and transferrin saturation with CER were assessed by multivariable logistic regression. Furthermore, mouse C2C12 skeletal myoblasts and differentiated myocytes were subjected to deferoxamine with or without ferric citrate. Myoblast proliferation was measured with a colorimetric 5‐bromo‐2′‐deoxy‐uridine ELISA assay. Myocyte differentiation was assessed using Myh7‐stainings. Myocyte energy metabolism, oxygen consumption rate and extracellular acidification rate were assessed using Seahorse mitochondrial flux analysis, and apoptosis rate with fluorescence‐activated cell sorting. RNA sequencing (RNAseq) was used to identify ID‐related gene and pathway enrichment in myoblasts and myocytes. Results Participants in the lowest age‐ and sex‐specific quintile of plasma ferritin (OR vs middle quintile 1.62, 95% CI 1.25–2.10, P < 0.001) or transferrin saturation (OR 1.34, 95% CI 1.03–1.75, P = 0.03) had a significantly higher risk of being in the lowest age‐ and sex‐specific quintile of CER, independent of body mass index, estimated GFR, haemoglobin, hs‐CRP, urinary urea excretion, alcohol consumption and smoking status. In C2C12 myoblasts, deferoxamine‐induced ID reduced myoblast proliferation rate (P‐trend <0.001) but did not affect differentiation. In myocytes, deferoxamine reduced myoglobin protein expression (−52%, P < 0.001) and tended to reduce mitochondrial oxygen consumption capacity (−28%, P = 0.10). Deferoxamine induced gene expression of cellular atrophy markers Trim63 (+20%, P = 0.002) and Fbxo32 (+27%, P = 0.048), which was reversed by ferric citrate (−31%, P = 0.04 and −26%, P = 0.004, respectively). RNAseq indicated that both in myoblasts and myocytes, ID predominantly affected genes involved in glycolytic energy metabolism, cell cycle regulation and apoptosis; co‐treatment with ferric citrate reversed these effects. Conclusions In population‐dwelling individuals, ID is related to lower muscle mass, independent of haemoglobin levels and potential confounders. ID impaired myoblast proliferation and aerobic glycolytic capacity, and induced markers of myocyte atrophy and apoptosis. These findings suggest that ID contributes to loss of muscle mass.

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Section: Discussionmentioning

confidence: 99%

Iron deficiency is related to lower muscle mass in community‐dwelling individuals and impairs myoblast proliferation

Vinke

Gorter

Eisenga

et al. 2023

J cachexia sarcopenia muscle

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“…Testicular copper depletion reduces fertility in male rats, while also impairing Fe and Zn homeostasis [ 70 ]. In addition, low iron can alter spermatogenesis and testicular morphology [ 71 ]. Furthermore, manganese depletion can lead to complete sterility due to the lack of spermatozoa production [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Trace Metal Accumulation in Rats Exposed to Mine Waters: A Case Study, Bor Area (Serbia)

Caraba,

Hutanu

et al. 2023

Toxics

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Zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), cadmium (Cd), and lead (Pb) levels were measured in the Bor City water supply system (control) and two watercourses exposed to mining wastewaters, i.e., the Lutarica River (one site) and the Kriveljska River (two sites). The same parameters were determined in the brain, heart, lungs, stomach, liver, spleen, kidneys, and testes of male Wistar rats given water from these sources for 2 months. Water Cu, Fe, Cd, and Pb were outside the safe range, excepting the reference site. Significant impacts on intra-organ metal homeostasis were detected, especially in the brain, stomach, kidneys, and testes. The dynamics and magnitude of these changes (versus controls) depended on the target organ, analyzed metal, and water origin. The greatest number of significant intra-organ associations between essential and non-essential metals were found for Cd-Zn, Cd-Cu, and Cd-Mn. A regression analysis suggested the kidneys as the most relevant organ for monitoring water manganese, and the stomach and brain for lead. These results highlight the environmental risks associated with mining wastewaters from the Bor area and could help scientists in mapping the spatial distribution and severity of trace metal contamination in water sources.

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“…In addition to altering the microbiota, iron de ciency interferes with the expression of genes involved in spermatogenic activity, resulting in impairment of male reproductive function [44]. Iron de ciency also increases oxidative stress in the testes, and iron supplementation can mitigate oxidative damage and repair testicular dysfunction [45].…”

Section: Discussionmentioning

confidence: 99%

High-fat diet impairs male fertility by disrupting Divalent metal transporter 1 and miR-135b in the gut-testis axis

Zhang

et al. 2023

Preprint

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Background Obese patients have been found to be susceptible to iron deficiency, and malabsorption of dietary iron is the cause of obesity-related iron deficiency (ORID). Divalent metal transporter 1 (DMT1) and ferroportin (FPN), are two transmembrane transporter proteins expressed in the duodenum that are closely associated with iron absorption. However, there have been few studies on the association between these two proteins and the increased susceptibility to iron deficiency in obese patients. Chronic inflammation is also thought to be a cause of obesity-related iron deficiency, and both conditions can have an impact on spermatogenesis and impair male reproductive function. Based on previous studies, transgenerational epigenetic inheritance through gametes was observed in obesity. Results Our results showed that obese mice had decreased blood iron levels (p < 0.01), lower protein and mRNA expression for duodenal DMT1 (p < 0.05), but no statistically significant variation in mRNA expression for duodenal FPN (p > 0.05); there was an increase in sperm miR-135b expression (p < 0.05). Bioinformatics revealed ninety overlapping genes and further analysis showed that they were primarily responsible for epithelial cilium movement, fatty acid beta-oxidation, protein dephosphorylation, fertilization and glutamine transport, which are closely related to spermatogenesis, sperm development and sperm viability in mice. Conclusions In conclusion, this study demonstrated that high-fat diet impairs male fertility by disrupting DMT1 and miR-135b in the gut-testis axis.

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Effects of Iron Supplementation on Testicular Function and Spermatogenesis of Iron-Deficient Rats

Cited by 18 publications

References 47 publications

Iron deficiency is related to lower muscle mass in community‐dwelling individuals and impairs myoblast proliferation

Iron deficiency is related to lower muscle mass in community‐dwelling individuals and impairs myoblast proliferation

Trace Metal Accumulation in Rats Exposed to Mine Waters: A Case Study, Bor Area (Serbia)

High-fat diet impairs male fertility by disrupting Divalent metal transporter 1 and miR-135b in the gut-testis axis

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