Expression of this gene decreases in oocyte of aging primate ovaries (Wang et al 2020) Single-Cell Transcriptomic Atlas of Primate Ovarian Aging. Wang S et al. (2020) Molecular mechanisms of ovarian aging and female age-related fertility decline remain unclear. We surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates (NHPs) and identified seven ovarian cell types with distinct gene-expression signatures, including oocyte and six types of ovarian somatic cells. In-depth dissection of gene-expression dynamics of oocytes revealed four subtypes at sequential and stepwise developmental stages. Further analysis of cell-type-specific aging-associated transcriptional changes uncovered the disturbance of antioxidant signaling specific to early-stage oocytes and granulosa cells, indicative of oxidative damage as a crucial factor in ovarian functional decline with age. Additionally, inactivated antioxidative pathways, increased reactive oxygen species, and apoptosis were observed in granulosa cells from aged women. This study provides a comprehensive understanding of the cell-type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders.//////////////////. ////////
The enzyme glutathione reductase (GR) recycles oxidized glutathione (GSSG) by converting it to the reduced form
(GSH) in an NADPH-dependent manner.
NCBI Summary:
This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. This enzyme is a homodimeric flavoprotein. It is a central enzyme of cellular antioxidant defense, and reduces oxidized glutathione disulfide (GSSG) to the sulfhydryl form GSH, which is an important cellular antioxidant. Rare mutations in this gene result in hereditary glutathione reductase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Aug 2010]
General function
Enzyme, Oxidoreductase
Comment
Eliasson M, et al 1999 reported the levels and subcellular distributions of detoxifying enzymes,including non-protein thiols and glutathione reductase, in the ovarian corpus luteum of the pregnant and non-pregnant pig. In the case of the mitochondrial fraction from pregnant corpus luteum, GPX and GRD displayed significant increases in specific activity. In the case of the mitochondrial fraction from pregnant corpus luteum, GPX and GRD displayed significant increases in specific activity. Upon subfractionation of the mitochondrial fraction (i.e. mitoplast preparation), SOD activity was distributed equally between the mitoplasts and the supernatant. CAT and GPX activities were mainly recovered in the supernatant, while the major GRD activity pelleted with the mitoplasts.
Cellular localization
Cytoplasmic
Comment
Ovarian function
Oogenesis, Oocyte maturation
Comment
Expression regulated by
Comment
Ovarian localization
Oocyte, Granulosa, Luteal cells, Stromal cells
Comment
Tomoko Kaneko et al 2001 reported the alteration of Glutathione Reductase (GR) Expression in the Female Reproductive Organs During the Estrous
Cycle.
A specific antibody raised against recombinant rat GR was used to localize
the protein in the female reproductive organs during the estrous cycle in the rat. In the ovary, the strongest reactivity to
the antibody was observed in oocytes, followed by granulosa cells, corpus luteum, and interstitial cells. The expression of the GR mRNA was highest during metestrus. Because GSH is known to increase gamete
viability and the efficiency of fertility, GR, which is expressed in these tissues, is predicted to play a pivotal role in the
reproduction process as a source of GSH.
Regulation of redox metabolism in the mouse oocyte and embryo. Dumollard R et al. Energy homeostasis of the oocyte is a crucial determinant of fertility. Following ovulation, the oocyte is exposed to the unique environment of the Fallopian tube, and this is reflected in a highly specialised biochemistry. The minute amounts of tissue available have made the physiological analysis of oocyte intermediary metabolism almost impossible. We have therefore used confocal imaging of mitochondrial and cytosolic redox state under a range of conditions to explore the oxidative metabolism of intermediary substrates. It has been known for some time that the early mouse embryo metabolises external pyruvate and lactate but not glucose to produce ATP. We now show at the level of single oocytes, that supplied glucose has no effect on the redox potential of the oocyte. Pyruvate is a cytosolic oxidant but a mitochondrial reductant, while lactate is a strong cytosolic reductant via the activity of lactate dehydrogenase. Unexpectedly, lactate-derived pyruvate appears to be diverted from mitochondrial oxidation. Our approach also reveals that the level of reduced glutathione (GSH) in the oocyte is maintained by glutathione reductase, which oxidises intracellular NADPH to reduce oxidised glutathione. Surprisingly, NADPH does not seem to be supplied by the pentose phosphate pathway in the unfertilised oocyte but rather by cytosolic NADP-dependent isocitrate dehydrogenase. Remarkably, we also found that the oxidant action of pyruvate impairs development, demonstrating the fundamental importance of redox state on early development.