Investigating the effects of dietary folic acid on sperm count, DNA damage and mutation in Balb/c mice

Increasing male infertility of unknown aetiology can be associated with environmental factors. Extensive use of mobile phones has exposed the general population to unprecedented levels of radiofrequency radiations (RFRs) that may adversely affect male reproductive health. Therefore, the present study investigated the effect of RFR Global System for Mobile communication (GSM) type, 900 MHz and melatonin supplementation on germ cell development during spermatogenesis. Swiss albino mice were divided into four groups. One group received RFR exposure for 3 h twice/day for 35 days and the other group received the same exposure but with melatonin ( N-acetyl-5-methoxytryptamine) (MEL; 5 mg/kg bw/day). Two other groups received only MEL or remain unexposed. Sperm head abnormality, total sperm count, biochemical assay for lipid peroxides, reduced glutathione, superoxide dismutase activity and testis histology were evaluated. Additionally, flow cytometric evaluation of germ cell subtypes and comet assay were performed in testis. Extensive DNA damage in germ cells of RFR-exposed animals along with arrest in pre-meiotic stages of spermatogenesis eventually leading to low sperm count and sperm head abnormalities were observed. Furthermore, biochemical assays revealed excess free radical generation resulting in histological and morphological changes in testis and germ cells morphology, respectively. However, these effects were either diminished or absent in RFR-exposed animals supplemented with melatonin. Hence, it can be concluded that melatonin inhibits pre-meiotic spermatogenesis arrest in male germ cells through its anti-oxidative potential and ability to improve DNA reparative pathways, leading to normal sperm count and sperm morphology in RFR-exposed animals.

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Amelioration of sperm count and sperm quality by lycopene supplementation in irradiated mice

Reproduction Fertility and Development ◽

10.1071/rd19433 ◽

2020 ◽

Vol 32 (12) ◽

pp. 1040

Author(s):

Małgorzata M. Dobrzyńska ◽

Aneta Gajowik

Keyword(s):

Dna Damage ◽

Sperm Quality ◽

Sperm Count ◽

Combined Treatment ◽

Treatment Groups ◽

Patients With Cancer ◽

Equivalent Time ◽

Radiation Induced ◽

Almost All ◽

Harmful Effects

Male mice were exposed to lycopene (LYC; 0.15 and 0.30mg kg−1) and irradiation (0.5, 1 Gy) alone or in combination (0.5 Gy+0.15mg kg−1 LYC; 0.5 Gy+0.30mg kg−1 LYC; 1 Gy+0.15mg kg−1 LYC; 1 Gy+0.30mg kg−1 LYC) for 2 weeks. LYC administration in the drinking water was started 24h or on Day 8 after the first irradiation dose or equivalent time point for groups treated with LYC alone. Sperm count, motility, morphology and DNA damage were determined at the end of the 2-week treatment period. Irradiation deteriorated sperm count and quality. Supplementation with LYC from 24h significantly increased the sperm count compared with irradiation alone. In almost all combined treatment groups, the percentage of abnormal spermatozoa was significantly decreased compared with that after irradiation alone. In some cases, combined treatment reduced levels of DNA damage in gametes. Both doses of LYC administered from Day 8 significantly reduced the percentage of morphologically abnormal spermatozoa compared with that seen after 1 Gy irradiation and reduced DNA damage in all combined treatment groups. In conclusion, LYC supplementation after irradiation can ameliorate the harmful effects of irradiation on gametes. Mitigation of radiation-induced damage in germ cells following LYC administration may be useful for radiological accidents and to protect non-treated tissues in patients with cancer undergoing radiotherapy.

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α-Lipoic acid attenuates transplacental nicotine-induced germ cell and oxidative DNA damage in adult mice

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2015-0151 ◽

2016 ◽

Vol 27 (6) ◽

Cited By ~ 4

Author(s):

Santo K. Anto ◽

Naresh Koyada ◽

Sabbir Khan ◽

Gopabandhu Jena

Keyword(s):

Dna Damage ◽

Germ Cell ◽

Lipoic Acid ◽

Oxidative Dna Damage ◽

Sperm Count ◽

Protective Role ◽

Sperm Head ◽

Smoking During Pregnancy ◽

Adult Mice ◽

Testicular Weight

AbstractBackground:Smoking during pregnancy is associated with numerous fetal and developmental complications and reproductive dysfunctions in the offspring. Nicotine is one of the key chemicals of tobacco responsible for addiction. The present study was aimed to investigate the protective role of α-lipoic acid (ALA) during the transplacental nicotine-induced germ cell and DNA damage in the offspring of Swiss mice.Methods:Pregnant mice were treated with nicotine (20 mg/kg/day) in drinking water from 10 to 20 days of gestation period, and ALA (120 mg/kg/day) was administered orally for the same period. Endpoint of evaluation includes general observations at delivery and throughout the study, litter weight and size, sperm count and sperm head morphology, while structural damages and protein expression were assessed by histology and immunohistochemistry, respectively.Results:Maternal nicotine exposure led to decreased growth rate, litter and testicular weight, testosterone level, 3β-HSD expression and sperm count as well as increased sperm head abnormalities, micronucleus frequency and 8-oxo-dG positive cells, and the effects have been restored by ALA supplementation.Conclusions:The present study clearly demonstrated that ALA ameliorates nicotine-associated oxidative stress, DNA damage and testicular toxicity in the offspring by improving steroidogenesis, spermatogenesis and sperm count.

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Changes in dietary folate intake differentially affect oxidised lipid and mitochondrial DNA damage in various brain regions of rats in the absence/presence of intracerebroventricularly injected amyloid β-peptide challenge

British Journal Of Nutrition ◽

10.1017/s0007114510005052 ◽

2011 ◽

Vol 105 (9) ◽

pp. 1294-1302 ◽

Cited By ~ 11

Author(s):

Ta-Fu Chen ◽

Ming-Jang Chiu ◽

Chou-Tz Huang ◽

Ming-Chi Tang ◽

Sue-Jane Wang ◽

...

Keyword(s):

Lipid Peroxidation ◽

Dna Damage ◽

Folic Acid ◽

Neuronal Death ◽

Brain Regions ◽

Folate Intake ◽

Amyloid Β Peptide ◽

Aβ Peptide ◽

Dietary Folate ◽

Dietary Folate Intake

Accumulating evidence suggests that changes in dietary folate intake may modulate the risks of Alzheimer's disease (AD) through as yet unknown mechanisms. The aims of the present study were to investigate how dietary folate affects the brain folate distribution, levels of oxidised lipid and DNA damage in the absence/presence of β-amyloid(25–35)(Aβ) peptide challenge, a pathogenic hallmark of AD. Male Wistar rats were assigned to diets with folic acid at 0 (folate deprivation; FD), 8 (moderate folate; MF) and 8 mg folic acid/kg diet+0·003 % in drinking-water (folate supplementation; FS) for 4 weeks. A single injection of Aβ peptide (1 mg/ml) or the vehicle solution was intracerebroventricularly (icv) administrated to rats a week before killing. Brain folate, a marker of oxidative injury, and neuronal death were assayed. In the absence of an Aβ injection, FD rats showed reduced folate levels, and increased 2-thiobarbituric acid-reactive substances and a mitochondrial (mt)DNA 4834 bp large deletion (mtDNA4834deletion) in the hippocampus compared with the counterpart brains of control rats (P < 0·05). A single icv injection of Aβ peptide potentiated lipid peroxidation in the medulla of FD rats, which was ameliorated by feeding FD rats with the MF and FS diets (P < 0·05). Feeding the FS diet to Aβ-injected rats enriched brain folate levels and reduced mtDNA4834deletion in the hippocampal and medullary regions compared with corresponding tissues of Aβ+FD rats (P < 0·05). Aβ+FS rats had reduced rates of neuronal death in the frontal cortex compared with Aβ+FD rats (P < 0·05). Taken together, our data revealed that folate deprivation differentially depleted brain folate levels, and increased lipid peroxidation and mtDNA4834deletions, particularly, in the hippocampus. Upon Aβ challenge, the FS diet may protect various brain regions against lipid peroxidation, mitochondrial genotoxicity and neural death associated with folate deprivation.

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Protective effects of folic acid on DNA damage and DNA methylation levels induced by N-methyl-N′-nitro-N-nitrosoguanidine in Kazakh esophageal epithelial cells

Human & Experimental Toxicology ◽

10.1177/0960327118769709 ◽

2018 ◽

Vol 37 (12) ◽

pp. 1258-1267

Author(s):

Y Chen ◽

H Feng ◽

D Chen ◽

K Abuduwaili ◽

X Li ◽

...

Keyword(s):

Dna Methylation ◽

Dna Damage ◽

Folic Acid ◽

Epithelial Cells ◽

Methylenetetrahydrofolate Reductase ◽

Folate Receptor ◽

Protective Effects ◽

Genome Wide ◽

Esophageal Epithelial Cells

The protective effects of folic acid on DNA damage and DNA methylation induced by N-methyl- N′-nitro- N-nitrosoguanidine (MNNG) in Kazakh esophageal epithelial cells were investigated using a 3 × 3 factorial design trial. The cells were cultured in vitro and exposed to media containing different concentrations of folic acid and MNNG, after which growth indices were detected. DNA damage levels were measured using comet assays, and genome-wide DNA methylation levels (MLs) were measured using high-performance liquid chromatography. The DNA methylation of methylenetetrahydrofolate reductase (MTHFR) and folate receptor- α (FR α) genes was detected by bisulfite sequencing polymerase chain reaction (PCR). The results showed significant increases in tail DNA concentration, tail length, and Olive tail moment ( p < 0.01); a significant reduction of genome-wide DNA MLs ( p < 0.01); and an increase in the methylation frequencies of MTHFR and FR α genes. In particular, significant differences were observed in the promoter regions of both genes ( p < 0.01). Our study indicated that a reduction in folic acid concentration promotes DNA damage and DNA methylation in Kazakh esophageal epithelial cells upon MNNG exposure. Thus, sufficient folic acid levels could play a protective role against the damage induced by this compound.

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Radiofrequency radiation (900 MHz)-induced DNA damage and cell cycle arrest in testicular germ cells in swiss albino mice

Toxicology and Industrial Health ◽

10.1177/0748233716671206 ◽

2016 ◽

Vol 33 (4) ◽

pp. 373-384 ◽

Cited By ~ 9

Author(s):

Neelam Pandey ◽

Sarbani Giri ◽

Samrat Das ◽

Puja Upadhaya

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Germ Cell ◽

Germ Cells ◽

Sperm Count ◽

Exposure Period ◽

Swiss Albino Mice ◽

Radiofrequency Radiation ◽

Post Exposure ◽

Albino Mice

Even though there are contradictory reports regarding the cellular and molecular changes induced by mobile phone emitted radiofrequency radiation (RFR), the possibility of any biological effect cannot be ruled out. In view of a widespread and extensive use of mobile phones, this study evaluates alterations in male germ cell transformation kinetics following RFR exposure and after recovery. Swiss albino mice were exposed to RFR (900 MHz) for 4 h and 8 h duration per day for 35 days. One group of animals was terminated after the exposure period, while others were kept for an additional 35 days post-exposure. RFR exposure caused depolarization of mitochondrial membranes resulting in destabilized cellular redox homeostasis. Statistically significant increases in the damage index in germ cells and sperm head defects were noted in RFR-exposed animals. Flow cytometric estimation of germ cell subtypes in mice testis revealed 2.5-fold increases in spermatogonial populations with significant decreases in spermatids. Almost fourfold reduction in spermatogonia to spermatid turnover (1C:2C) and three times reduction in primary spermatocyte to spermatid turnover (1C:4C) was found indicating arrest in the premeiotic stage of spermatogenesis, which resulted in loss of post-meiotic germ cells apparent from testis histology and low sperm count in RFR-exposed animals. Histological alterations such as sloughing of immature germ cells into the seminiferous tubule lumen, epithelium depletion and maturation arrest were also observed. However, all these changes showed recovery to varied degrees following the post-exposure period indicating that the adverse effects of RFR on mice germ cells are detrimental but reversible. To conclude, RFR exposure-induced oxidative stress causes DNA damage in germ cells, which alters cell cycle progression leading to low sperm count in mice.

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Combined action of X-rays and nonylphenol on mouse sperm

Open Life Sciences ◽

10.2478/s11535-011-0021-0 ◽

2011 ◽

Vol 6 (3) ◽

pp. 320-329 ◽

Cited By ~ 2

Author(s):

Małgorzata Dobrzyńska

Keyword(s):

Dna Damage ◽

Germ Cells ◽

Sperm Morphology ◽

Sperm Count ◽

X Rays ◽

Combined Exposure ◽

X Ray ◽

Combined Action ◽

Sperm Count And Morphology ◽

Higher Doses

AbstractThe aim of this study was to assess the effects of 2-weeks’ X-ray and/or nonylphenol (NP) exposure on male mice’s sperm count and quality. Pzh:SFIS mice were exposed to X-rays (0.05 Gy, 0.10 Gy, 0.20 Gy) or to nonylphenol (25 mg/kg bw, 50 mg/kg bw, 100 mg/kg bw) or to both agents (0.05 Gy + 25 mg/kg bw NP, 0.10 Gy + 50 mg/kg bw NP). At 24 h and 5 weeks after the end of exposure the sperm count, morphology and frequency of DNA damage in the male germ cells were estimated. Each agent alone diminished sperm count and morphology. The dose of 0.05 Gy of X-rays decreased the frequency of DNA damage. Combined exposure to lower doses of both agents significantly improved sperm morphology and decreased the level of DNA damage compared to one agent alone. Combined exposure to higher doses reduced the frequency of DNA damage compared to the effect of the appropriate dose of NP. Results of combined exposure to low doses of both agents suggest that 0.05 Gy of X-rays stimulate the DNA damagecontrol system and in consequence repair of DNA caused by X-rays and NP. It may be correlated with increased antioxidant capacity.

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Oral Antioxidant Treatment of Men Significantly Improves the Reproductive Outcome of IVF Cycles

Journal of Clinical Medicine ◽

10.3390/jcm10153254 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3254

Author(s):

Paola Scaruffi ◽

Emanuele Licata ◽

Elena Maccarini ◽

Claudia Massarotti ◽

Francesca Bovis ◽

...

Keyword(s):

Folic Acid ◽

Lipoic Acid ◽

Coenzyme Q10 ◽

Sperm Count ◽

Sperm Concentration ◽

Semen Parameters ◽

Alpha Lipoic Acid ◽

Antioxidant Treatment ◽

Blastocyst Development ◽

Fertilization Rates

Some 30% to 80% of male sub-fertility may be associated with oxidative stress that damages spermatozoa and can decrease success of in vitro fertilization (IVF) techniques. This multicenter, longitudinal, prospective study aimed to investigate whether oral antioxidant supplementation improved the reproductive competence of men who had had low fertilization rates in their previous intracytoplasmic sperm injection (ICSI) cycles without azoospermia or severe oligozoospermia or any identifiable andrological disease. Seventy-seven men from couples who had an ICSI attempt with unexplained <60% fertilization rate took an antioxidant mix of myo-inositol, alpha-lipoic acid, folic acid, coenzyme Q10, zinc, selenium, and vitamins B2, B6, and B12. Semen parameters were analyzed before (T0) and after 90 days (T90) of treatment, and outcomes of the paired T0 and T90 cycles were compared. After the treatment there was an increase in sperm concentration (p = 0.027), total motile sperm count (p = 0.003), progressive motility (p < 0.0001), and a decreasing trend of DNA-fragmented spermatozoa. Embryological outcomes (fertilization, embryo quality, blastocyst development) were significantly higher in T90 than T0 cycles. No T0 cycle resulted in an evolutive pregnancy. Conversely, in T90 cycles 29 singleton clinical pregnancies were obtained. No negative neonatal outcomes were recorded in newborns after antioxidant treatment. Diet supplementation of men who have had low fertilization rates in their previous ICSI cycles with a combination of myo-inositol, alpha-lipoic acid, folic acid, coenzyme Q10, zinc, selenium, betaine, and vitamins may improve semen reproductive potential and ICSI clinical outcome.

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Vapor cannabis exposure generationally affects male reproductive functions in mice

10.1101/2021.08.22.457271 ◽

2021 ◽

Author(s):

Mingxin Shi ◽

Esther M. Langholt ◽

Logan C. Butler ◽

Madeleine E. Harvey ◽

Emma C. Wheeler ◽

...

Keyword(s):

Dna Damage ◽

Germ Cells ◽

Sperm Count ◽

Plant Matter ◽

Abnormal Distribution ◽

Morphometric Analyses ◽

Drug Naïve ◽

Neonatal Testis ◽

Air Control ◽

Dnmt1 Expression

This study was performed to examine whether vapor exposure to cannabis plant matter negatively impacts male reproductive functions and testis development in mice. Adult CD-1 male mice (F0) were exposed to air (control) or 200 mg of vaporized cannabis plant matter 3x/day over a 10 day period. Subsequently, F0 males were bred with drug naive CD-1 females to generate F1 males, and F1 offspring were used to generate F2 males. Cannabis vapor exposure decreased sperm count and/or motility in F0 and F1 males and disrupted the progression of germ cell development, as morphometric analyses exhibited an abnormal distribution of the stages of spermatogenesis in F0 males. Although plasma levels of testosterone were not affected by cannabis exposure in any ages or generations of males, dysregulated steroidogenic enzymes, Cyp11a1 and Cyp19a1, were observed in F0 testis. In the neonatal testis from F1 males, while apoptosis was not altered, DNA damage and DNMT1, but not DNMT3A and DNMT3B, were increased in germ cells following cannabis exposure. In contrast, the alterations of DNA damage and DNMT1 expression were not observed in F2 neonatal males. These results suggest that cannabis vapor exposure generationally affects male reproductive functions, probably due to disruption of spermatogenesis in the developing testis.

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