Thioredoxin, an antioxidant redox protein, in ovarian follicles of women undergoing &lt;i&gt;in vitro&lt;/i&gt; fertilization

Kishi, Ikuko; Ohishi, Miho; Akiba, Yasuo; Asada, Hironori; Konishi, Yasuhiro; Nakano, Masao; Kamei, K.; Yoshimura, Yasunori; Maruyama, Tetsuo

doi:10.1507/endocrj.ej15-0210

Cited by 11 publications

(6 citation statements)

References 37 publications

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“…The PRDX4 protein, and mRNA, mainly expressed in the granulosa cells of mature human follicles, was reported lower in PCOS patients as compared to controls, possibly due to increased oxidative stress in the follicles of PCOS patients [52]. A deficiency of mitochondrial redox protein TXN2 was recently associated with earlyonset neuro-degeneration [53]. Here, patient-derived samples exhibited increased ROS levels, impaired free radical defence and showed oxidative phosphorylation dysfunction.…”

Section: Discussionmentioning

confidence: 74%

“…Here, patient-derived samples exhibited increased ROS levels, impaired free radical defence and showed oxidative phosphorylation dysfunction. Furthermore, upon cell culture antioxidant treatment (MitoQ, Idebenone, Trolox), these detrimental effects were counteracted [53]. The transcript level of TXN2 was previously reported significantly higher in granulosa cells of normally responding women undergoing IVF treatment as compared to poor responders [54].…”

Section: Discussionmentioning

confidence: 90%

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Transcripts encoding free radical scavengers in human granulosa cells from primordial and primary ovarian follicles

Ernst

Lykke‐Hartmann

2018

J Assist Reprod Genet

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The results indicate extensive energy production and free radical scavenging in the granulosa cells of primordial follicles with potential implications for ovarian ageing, cigarette smoking, premature ovarian failure and polycystic ovarian syndrome. Furthermore, DJ-1 may be involved in androgen responsiveness and the regulation of follicle growth via PI3K/PTEN/AKT signalling pathway regulation in the granulosa cells of primary follicles. The involvement of mitochondrial free radical production in the age-related decline of competent oocytes is becoming apparent.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 90%

Transcripts encoding free radical scavengers in human granulosa cells from primordial and primary ovarian follicles

Ernst

Lykke‐Hartmann

2018

J Assist Reprod Genet

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“…Moreover, obese women had higher follicular fluid oxidative stress markers [ 127 ]. Thioredoxin, a component of the TRX/TRXR system induced by oxidative stress-generating stimuli and involved in antioxidant defense mechanisms, was present throughout follicular development in women and was also identified in follicular fluid [ 125 , 128 , 129 ]. The predicted activation of the thioredoxin pathway following treatment with both insulin and high fat could suggest an enhanced oxidative environment compared to high fat exposure alone or insulin alone.…”

Section: Discussionmentioning

confidence: 99%

Gene cascade analysis in human granulosa tumor cells (KGN) following exposure to high levels of free fatty acids and insulin

2021

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Maternal metabolic disorders such as obesity and diabetes are detrimental factors that compromise fertility and the success rates of medically assisted procreation procedures. During metabolic stress, adipose tissue is more likely to release free fatty acids (FFA) in the serum resulting in an increase of FFA levels not only in blood, but also in follicular fluid (FF). In humans, high concentrations of palmitic acid and stearic acid reduced granulosa cell survival and were associated with poor cumulus-oocyte complex (COC) morphology. Obesity and high levels of circulating FFA were also causatively linked to hampered insulin sensitivity in cells and compensatory hyperinsulinemia. To provide a global picture of the principal upstream signaling pathways and genomic mechanisms involved in this metabolic context, human granulosa-like tumor cells (KGN) were treated with a combination of palmitic acid, oleic acid, and stearic acid at the higher physiological concentrations found in the follicular fluid of women with a higher body mass index (BMI) (≥ 30.0 kg/m2). We also tested a high concentration of insulin alone and in combination with high concentrations of fatty acids. Transcription analysis by RNA-seq with a cut off for fold change of 1.5 and p-value 0.05 resulted in thousands of differentially expressed genes for each treatment. Using analysis software such as Ingenuity Pathway Analysis (IPA), we were able to establish that high concentrations of FFA affected the expression of genes mainly related to glucose and insulin homoeostasis, fatty acid metabolism, as well as steroidogenesis and granulosa cell differentiation processes. The combination of insulin and high concentrations of FFA affected signaling pathways related to apoptosis, inflammation, and oxidative stress. Taken together, our results provided new information on the mechanisms that might be involved in human granulosa cells exposed to high concentrations of FFA and insulin in the contexts of metabolism disorders.

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“…Peritoneal fluid from women with endometriosis has pro-oxidant status due to an imbalance between ROS generation and antioxidant defense systems, resulting in less efficient protection of oocytes. Antioxidants such as vitamin C, vitamin E, thioredoxin, SOD, and glutathione have been found to be lower in follicular fluid from infertile patients with endometriosis than in women with non-endometriosisrelated infertility [130][131][132][133]. Despite robust evidence showing altered redox balance in the pelvic and intrafollicular environment in the case of endometriosis, supplementation with immunomodulators able to decrease inflammation and oxidative stress, such as pentoxifylline [134], or indeed antioxidants such as vitamin C and E [135,136], failed to yield any advantage in terms of pregnancy rates.…”

Section: Targeting Oxidative Stress To Treat Endometriosis-related Infertilitymentioning

confidence: 99%

Can Endometriosis-Related Oxidative Stress Pave the Way for New Treatment Targets?

Cacciottola

Donnez

Dolmans

2021

IJMS

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Endometriosis is a disease of reproductive age characterized by chronic pelvic pain and infertility. Its pathogenesis is complex and still partially unexplained. However, there is increasing evidence of the role of chronic inflammation, immune system dysregulation, and oxidative stress in its development and progression. The latter appears to be involved in multiple aspects of the disease. Indeed, disease progression sustained by a hyperproliferative phenotype can be related to reactive oxygen species (ROS) imbalance, as numerous experiments using drugs to counteract hyperproliferation have shown in recent years. Chronic pelvic pain is also associated with cell function dysregulation favoring chronic inflammation and oxidative stress, specifically involving macrophages and mast cell activation. Moreover, there is increasing evidence of a role for ROS and impaired mitochondrial function not only as deleterious effectors of the ovarian reserve in patients with endometriomas but also in terms of oocyte quality and, hence, embryo development impairment. Targeting oxidative stress looks to be a promising strategy to both curb endometriotic lesion progression and alleviate endometriosis-associated symptoms of chronic pain and infertility. More investigations are nevertheless needed to develop effective therapeutic strategies for clinical application.

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Thioredoxin, an antioxidant redox protein, in ovarian follicles of women undergoing <i>in vitro</i> fertilization

Cited by 11 publications

References 37 publications

Transcripts encoding free radical scavengers in human granulosa cells from primordial and primary ovarian follicles

Transcripts encoding free radical scavengers in human granulosa cells from primordial and primary ovarian follicles

Gene cascade analysis in human granulosa tumor cells (KGN) following exposure to high levels of free fatty acids and insulin

Can Endometriosis-Related Oxidative Stress Pave the Way for New Treatment Targets?

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