GPX4
Phospholipid hydroperoxide glutathione peroxidase precursor (EC 1.11.1.12) (PHGPx) (Glutathione peroxidase 4) (GPx-4) (GSHPx-4)
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Aging oocytes undergo various molecular, cellular, and biochemical changes. Aging of oocytes results in reduced embryo developmental capacity and blastocyst quality, which is thought to be caused partly by the accumulation of reactive oxygen species (ROS). This study aimed to determine the effect of l-carnitine (LC) on the development of embryos formed from aged oocytes in vitro. The development and quality of the blastocysts in the LC-treated group were significantly higher than those in the untreated aged group after in vitro fertilization (IVF). In addition, after LC treatment, the level of intracellular ROS in aged group significantly decreased, and glutathione (GSH) levels significantly increased compared with those in the untreated aged group. There was no significant difference in the mitochondrial membrane potential among the three groups. Moreover, ROS could induce autophagy and LC3 antibody was widely used as a marker for detecting autophagy. The fluorescence intensity of LC3 in the aged group was significantly higher than that of LC3 in the LC-treated group. Furthermore, Real-time reverse transcriptase-polymerase chain reaction showed that the mRNA levels of antioxidation genes GPX4 and SOD1 were significantly higher in embryos from LC-treated group than in those from the untreated aged group. In summary, our results indicated that LC can improve the developmental capacity of embryos from aging oocytes in vitro by reducing oxidative stress.
MeSH Terms
- Animals
- Carnitine
- Cattle
- Culture Media
- Embryo Culture Techniques
- Female
- Fertilization in Vitro
- In Vitro Oocyte Maturation Techniques
- Oocytes
- Oxidative Stress
Keywords
- Bovine
- Embryo development
- Oocyte aging
- l-carnitine
Female reproductive (ovarian) aging is distinctively characterized by a markedly reduced reproductive function due to a remarkable decline in quality and quantity of follicles and oocytes. Selenium (Se) has been implicated in playing many important biological roles in male fertility and reproduction; however, its potential roles in female reproduction, particularly in aging subjects, remain poorly elucidated. Therefore, in the current study we used a murine model of female reproductive aging and elucidated how different Se-levels might affect the reproductive efficiency in aging females. Our results showed that at the end of an 8-week dietary trial, whole-blood Se concentration and blood total antioxidant capacity (TAOC) were significantly reduced in Se-deficient (0.08 mg Se/kg; Se-D) mice, whereas both of these biomarkers were significantly higher in inorganic (0.33 mg/kg; ISe-S) and organic (0.33 mg/kg; OSe-S) Se-supplemented groups. Similarly, compared to the Se-D group, Se supplementation significantly ameliorated the maintenance of follicles and reduced the rate of apoptosis in ovaries. Meanwhile, the rate of in vitro-produced embryos resulting from germinal vesicle (GV) oocytes was also significantly improved in Se-supplemented (ISe-S and OSe-S) groups compared to the Se-D mice, in which none of the embryos developed to the hatched blastocyst stage. RT-qPCR results revealed that mRNA expression of [i]Gpx1[/i], [i]Gpx3[/i], [i]Gpx4, Selenof[/i], [i]p21[/i], and [i]Bcl-2[/i] genes in ovaries of aging mice was differentially modulated by dietary Se levels. A considerably higher mRNA expression of [i]Gpx1[/i], [i]Gpx3[/i], [i]Gpx4[/i], and [i]Selenof[/i] was observed in Se-supplemented groups compared to the Se-D group. Similarly, mRNA expression of [i]Bcl-2[/i] and [i]p21[/i] was significantly lower in Se-supplemented groups. Immunohistochemical assay also revealed a significantly higher expression of GPX4 in Se-supplemented mice. Our results reasonably indicate that Se deficiency (or marginal levels) can negatively impact the fertility and reproduction in females, particularly those of an advancing age, and that the Se supplementation (inorganic and organic) can substantiate ovarian function and overall reproductive efficiency in aging females.
Keywords
- GPX4
- Gpx1
- Gpx3
- Selenof
- apoptosis
- embryo
- follicle development
- ovarian aging
- selenium
- selenoprotein
To evaluate the effects of resveratrol on oocyte maturation in aged mice and humans. Experimental laboratory study. University-based reproductive medicine center. A total of 64 women 38-45 years of age undergoing intracytoplasmic sperm injection (ICSI) and 48-52-week-old female C57BL/6J mice. In vitro culture in the presence of three different concentrations of resveratrol (0.1, 1.0, and 10 μm) or dimethylsulfoxide. Parameters of oocyte nuclear maturation, fertilization, immunofluorescence intensity of mitochondria, and normal morphology of spindle and chromosome of oocytes undergoing in vitro maturation (IVM) in aged mice and humans; blastocyst formation and levels of SRIT1, CAT, SOD1, and GPX4 gene expressions in aged mice. Resveratrol at 1.0 μm significantly increased first polar body emission rate in oocytes derived from aged mice and humans, and an increased percentage of fertilization and blastocyst formation was observed in aged mice. In addition, immunofluorescence intensity of mitochondria and normal morphology of spindle and chromosome of oocytes undergoing IVM were notably improved compared with control samples in aged mice and human. Furthermore, the use of resveratrol exhibited enhanced expression patterns of SRIT1, CAT, SOD1, and GPX4 in aged mice. Resveratrol induced oocyte maturation and blastocyst formation in aged mice, and improved oocyte maturation and quality was examined in aged humans. In conclusion, 1.0 μm resveratrol was the appropriate concentration in IVM medium.
MeSH Terms
- Adult
- Aging
- Animals
- Antioxidants
- Dose-Response Relationship, Drug
- Female
- Humans
- In Vitro Oocyte Maturation Techniques
- Mice
- Mice, Inbred C57BL
- Middle Aged
- Oocytes
- Ovulation Induction
- Resveratrol
Keywords
- IVM
- Oocyte
- aged humans
- aged mice
- resveratrol
Menopause is characterized by the depletion of estrogen that has been proposed to cause oxidative stress. Circadian rhythm is an internal biological clock that controls physiological processes. It was analyzed the gene expression in peripheral blood mononuclear cells and the lipids and glucose levels in plasma of a subgroup of 17 pre-menopausal women, 19 men age-matched as control group for the pre-menopausal women, 20 post-menopausal women and 20 men age-matched as control group for the post-menopausal women; all groups were matched by body mass index. Our study showed a decrease in the expression of the oxidative stress-related gene GPX1, and an increase in the expression of SOD1 as consequence of menopause. In addition, we found that the circadian rhythm-related gene PER2 decreased as consequence of menopause. On the other hand, we observed a decrease in the expression of the oxidative stress-related gene GPX4 and an increase in the expression of CAT as a consequence of aging, independently of menopause. Our results suggest that the menopause-induced oxidative stress parallels a disruption in the circadian clock in women, and part of the differences in oxidative stress observed between pre- and post-menopausal women was due to aging, independent of menopause. Clinical Trials.gov.Identifier: NCT00924937.
MeSH Terms
- Adult
- Aging
- Biomarkers
- Catalase
- Circadian Rhythm
- Female
- Glutathione Peroxidase
- Humans
- Male
- Menopause
- Middle Aged
- Oxidative Stress
- Period Circadian Proteins
- Phospholipid Hydroperoxide Glutathione Peroxidase
- Superoxide Dismutase-1
Keywords
- Biology of aging
- Gender differences
- Genomics
- Oxidative stress
- Senescence
A high-fat diet during intrauterine development predisposes offspring (F ) to phenotypic alterations, such as lipid synthesis imbalance and increased oxidative stress, causing changes in male fertility. The objective of this study was to evaluate the effects of maternal obesity during pregnancy and lactation on antioxidant enzymes in the F testes. Female Wistar rats (F ) were fed either a control (C, 5% fat) or an obesogenic (MO, maternal obesity, 25% fat) diet from weaning and throughout subsequent pregnancy and lactation. F offspring were weaned to the control diet. Testes were retrieved at 110, 450 and 650 postnatal days (PND) for real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) antioxidant enzyme analyses. Catalase was similar between groups by RT-qPCR, whereas by IHC it was higher in the MO group at all ages than in the C group. Superoxide dismutase 1 (SOD1) had lower expression at PND 110 in MO than in C by both techniques; at PND 450 and 650 by immunoanalysis SOD1 was higher in MO than in C. Glutathione peroxidase 1 (GPX1), GPX2 and GPX4 by RT-qPCR were similar between groups and ages; by IHC GPX1/2 was higher in MO than in C, whereas GPX4 showed the opposite result at PND 110 and 450. In conclusion, antioxidant enzymes in the rat testes are modified with age. Maternal obesity negatively affects the F testicular antioxidant defence system, which, in turn, can explain the decrease in reproductive capacity.
MeSH Terms
- Aging
- Animals
- Antioxidants
- Catalase
- Diet, High-Fat
- Female
- Glutathione Peroxidase
- Male
- Maternal Nutritional Physiological Phenomena
- Obesity
- Oxidative Stress
- Pregnancy
- Prenatal Exposure Delayed Effects
- Rats
- Rats, Wistar
- Superoxide Dismutase
- Testis