Impact of hydrogen peroxide-driven Fenton reaction on mouse oocyte quality

Molecular & Cellular Proteomics

Cheng

et al. 2018

SummaryMaternal obesity has been reported to impair oocyte quality in mice, however, the underlying mechanisms remain unclear. In the present study, by conducting a comparative proteomic analysis, we identified a reduced expression of TIGAR protein in ovulated oocytes from high-fat diet (HFD)-fed mice. Specific depletion of TIGAR in mouse oocytes results in the marked elevation of reactive oxygen species (ROS) levels and the failure of meiotic apparatus assembly. Importantly, forced expression of TIGAR in HFD oocytes not only attenuates ROS production, but also partly prevents spindle disorganization and chromosome misalignment during meiosis. Meantime, we noted that TIGAR knockdown in oocytes induces a strong activation of autophagy, while overexpression of TIGAR significantly reduces the LC3 accumulation in HFD oocytes. By anti-oxidant treatment, we further demonstrated that such an autophagic response is dependent on the TIGAR-controlled ROS production. In summary, our data indicate a role for TIGAR in modulating redox homeostasis during oocyte maturation, and uncover that loss of TIGAR is a critical pathway mediating the effects of maternal obesity on oocyte quality.

Section: Discussionmentioning

confidence: 99%

Loss of TIGAR Induces Oxidative Stress and Meiotic Defects in Oocytes from Obese Mice

Molecular & Cellular Proteomics

Cheng

et al. 2018

Free Radical Biology and Medicine

“…This short incubation time also eliminates the effect of H 2 O 2 and Fe(II) alone as described previously. 17 The concentration of Fe(II), 100 mmol/ L, used in the current study to establish the Á OH generating system has been widely used in previous studies. 39 For HOCl treatment (experiments performed in triplicate), oocytes were divided into 4 different groups: (group 1, n ¼ 324) oocytes with CCs and (group 2, n ¼ 391) oocytes without CCs treated with increasing concentrations of HOCl (10,25,50, and 100 mmol/L); and (group 3, n ¼ 73) untreated oocytes with CCs and (group 4, n ¼ 64) untreated oocytes without CCs.…”

Section: Methodsmentioning

confidence: 99%

“…17,40 Subsequently, the oocytes were subjected to indirect immunofluorescence staining by incubating in mouse primary anti-a tubulin antibody against the microtubule morphology (MT) for 60 minutes and secondary FITC-conjugated antigoat antibody for 30 minutes. 40 The chromosomes were stained using PI and incubated for 15 minutes.…”

Section: Immunofluorescence Staining and Fluorescence Microscopymentioning

confidence: 99%

“…[12][13][14][15][16] Reactive oxygen species such as superoxide (O 2 Á À ), hydroxyl radical ( Á OH), hydrogen peroxide (H 2 O 2 ), and hypochlorous acid (HOCl) are highly disruptive to cellular function. 13,17,18 The major intracellular sources of H 2 O 2 are spontaneous production, superoxide dismutase-catalyzed reaction of O 2 Á À , 19,20,71 generation through the mitochondrial electron transport chain, and the nicotinamide adenine dinucleotide phosphate oxidase system in the cellular plasma membrane. 13,21,22,72 Hydrogen peroxide is found in physiologic concentrations ranging from 10 to 20 mmol/L and up to 100 mmol/L in pathologic circumstances.…”

Section: Introductionmentioning

confidence: 99%

“…[25][26][27][28] There are other ways that H 2 O 2 can indirectly affect oocyte quality, for example, we have recently shown that Á OH generated by the H 2 O 2 -induced Fenton reaction caused instantaneous oocyte damage, which has been estimated indirectly in plasma at levels of 250 to 500 mmol/L. 17,29 More recently, we have demonstrated that diffused intra-oocyte H 2 O 2 is normally found in the oocyte and its microenvironment. This H 2 O 2 , in the presence of chloride, can subsequently trigger the catalytic activity of MPO generating the toxic oxidant, HOCl, 20,30,73 a substance known to deteriorate oocyte quality.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Defensive Role of Cumulus Cells againstReactive Oxygen Species Insult in Metaphase II Mouse Oocytes

Shaeib¹,

Khan²,

Ali³

et al. 2014

Self Cite

We investigated the ability of reactive oxygen species (ROS), such as hydrogen peroxide (H 2 O 2 ), hydroxyl radical ( Á OH), and hypochlorous acid (HOCl), to overcome the defensive capacity of cumulus cells and elucidate the mechanism through which ROS differentially deteriorate oocyte quality. Metaphase II mouse oocytes with (n ¼ 1634) and without cumulus cells (n ¼ 1633) were treated with increasing concentration of ROS, and the deterioration in oocyte quality was assessed by the changes in the microtubule morphology and chromosomal alignment. Oocyte and cumulus cell viability and cumulus cell number were assessed by indirect immunofluorescence, staining of gap junction protein, and trypan blue staining. The treated oocytes showed decreased quality as a function of increasing concentrations of ROS when compared to controls. Cumulus cells show protection against H 2 O 2 and Á OH insult at lower concentrations, but this protection was lost at higher concentrations (>50 mmol/L). At higher H 2 O 2 concentrations, treatment dramatically influenced the cumulus cell number and viability with resulting reduction in the antioxidant capacity making the oocyte more susceptible to oxidative damage. However, cumulus cells offered no significant protection against HOCl at any concentration used. In all circumstances in which cumulus cells did not offer protection to the oocyte, both cumulus cell number and viability were decreased. Therefore, the deterioration in oocyte quality may be caused by one or more of the following: a decrease in the antioxidant machinery by the loss of cumulus cells, the lack of scavengers for specific ROS, and/or the ability of the ROS to overcome these defenses.

Oxidative stress in oocyte aging and female reproduction

Tang

Journal Cellular Physiology

et al. 2021

226

112

In a healthy body, reactive oxygen species (ROS) and antioxidants remain balanced. When the balance is broken toward an overabundance of ROS, oxidative stress appears and may lead to oocyte aging. Oocyte aging is mainly reflected as the gradual decrease of oocyte quantity and quality. Here, we aim to review the relationship between oxidative stress and oocyte aging. First, we introduced that the defective mitochondria, the age‐related ovarian aging, the repeated ovulation, and the high‐oxygen environment were the ovarian sources of ROS in vivo and in vitro. And we also introduced other sources of ROS accumulation in ovaries, such as overweight and unhealthy lifestyles. Then, we figured that oxidative stress may act as the “initiator” for oocyte aging and reproductive pathology, which specifically causes follicular abnormally atresia, abnormal meiosis, lower fertilization rate, delayed embryonic development, and reproductive disease, including polycystic ovary syndrome and ovary endometriosis cyst. Finally, we discussed current strategies for delaying oocyte aging. We introduced three autophagy antioxidant pathways like Beclin‐VPS34‐Atg14, adenosine 5‘‐monophosphate (AMP)‐activated protein kinase/mammalian target of rapamycin (AMPK/mTOR), and p62‐Keap1‐Nrf2. And we also describe the different antioxidants used to combat oocyte aging. In addition, the hypoxic (5% O2) culture environment for oocytes avoiding oxidative stress in vitro. So, this review not only contribute to our general understanding of oxidative stress and oocyte aging but also lay the foundations for the therapies to treat premature ovarian failure and oocyte aging in women.