Hyperandrogenism drives ovarian inflammation and pyroptosis: A possible pathogenesis of PCOS follicular dysplasia

Xiang, Yu; Wang, Hua; Ding, Huimin; Xu, Tianyue; Liu, Xiu; Huang, Zichao; Wu, Honghui; Ge, Hongshan

doi:10.1016/j.intimp.2023.111141

Cited by 15 publications

(3 citation statements)

References 68 publications

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“…Dysfunction in endocrine metabolism, abnormal androgen hormone levels, and chronic inflammation are observed in PCOS ( 8 ). While most studies have focused on the impact of hyperandrogenism on the pathological mechanisms of PCOS, particularly follicular dysplasia and anovulation, inflammation stands out as a critical risk factor among the main contributors to PCOS pathophysiology ( 35 , 36 ). Several studies have indicated that PCOS is associated with progressive inflammation of the ovarian follicles and a decline in ovarian function ( 13 , 37 ).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Pimpinella anisum Fruit Extract on Polycystic Ovary Syndrome in a Rat Model: Emerging Role of Inflammatory Responses and Oxidative Stress

Dadkhah,

Gholizadeh,

Nasimi Doost Azgomi

et al. 2024

Iran J Pharm Res

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Background: Polycystic ovary syndrome (PCOS) is the most common gynecological endocrine disorder. Objectives: This study evaluated the therapeutic effects of Pimpinella anisum L. (P. anisum) fruit on pro-inflammatory cytokines, oxidative stress markers, and ovarian tissue structure in a rat model of PCOS. Methods: After inducing PCOS, female Wistar rats were randomly divided into control and PCOS groups. They orally received daily doses of normal saline or hydro-alcoholic extract of P. anisum at two doses (200 and 400 mg/kg) for 21 days. At the end of the treatment period, ovarian and liver tissues were collected to measure lipid peroxidation, antioxidant status, TNF-α, IL-6 mRNA expression, and its content. Additionally, histopathological examinations of the ovarian tissue were conducted. Results: Our findings revealed a dose-dependent change in the biochemical and histopathological parameters. Treatment with P. anisum resulted in a significant decrease in TNF-α and IL-6 mRNA expression levels and their content in the ovarian and liver tissues. It also reduced MDA levels while increasing SOD and GPx activity in both ovarian and liver tissues of PCOS rats. Furthermore, the number of follicular cysts in the PCOS rat model was significantly reduced. Conclusions: The beneficial effects of P. anisum in PCOS rats are partly attributed to the inhibition of inflammatory and oxidative stress markers in ovarian tissue. These findings suggest that P. anisum could be a potential candidate for the treatment of PCOS disorders

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Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Pimpinella anisum Fruit Extract on Polycystic Ovary Syndrome in a Rat Model: Emerging Role of Inflammatory Responses and Oxidative Stress

Dadkhah,

Gholizadeh,

Nasimi Doost Azgomi

et al. 2024

Iran J Pharm Res

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“…In addition, CISD2 is located in the ER-mitochondria contacts (MERC) and has important regulatory effects on the mitochondria and ER [ 47 ]. Our previous studies have also found that HA induces ER stress in the FF of GCs from PCOS patients by causing inflammation, thus inducing NLRP3 expression and pyroptosis [ 48 ]. Whether CISD2 regulates the occurrence of endoplasmic reticulum stress in PCOS still needs further study ( Figure 8 ).…”

Section: Discussionmentioning

confidence: 99%

CISD2 regulates oxidative stress and mitophagy to maintain the balance of the follicular microenvironment in PCOS

Wu,

Zhu,

Liang

et al. 2024

Redox Report

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“…On the other hand, some experts believe that chronic inflammation is the primary factor behind androgen production and ovarian dysfunction. 74 …”

Section: Discussionmentioning

confidence: 99%

Randomized clinical trial of astaxanthin supplement on serum inflammatory markers and ER stress‐apoptosis gene expression in PBMCs of women with PCOS

Jabarpour,

Amidi,

Aleyasin

et al. 2024

J Cellular Molecular Medi

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Polycystic ovarian syndrome (PCOS) is related to pro‐apoptotic and pro‐inflammatory conditions generated by Endoplasmic reticulum (ER) stress. This study aimed to determine the effect of Astaxanthin (ASX), as carotenoid with potent antioxidant and anti‐inflammatory properties, on serum inflammatory markers, apoptotic factors and ER stress‐apoptotic genes in peripheral blood mononuclear cells (PBMCs) of women with PCOS. This randomized, double‐blind clinical trial included 56 PCOS patients aged 18–40. For 8 weeks, subjects were randomly assigned to one of two groups: either 12 mg ASX (n = 28) or placebo (n = 28). Real‐time PCR was used to quantify gene expression associated with ER stress‐apoptosis in PCOS women's PBMCs. The levels of TNF‐α, IL18, IL6 and CRP were determined by obtaining blood samples from all patients before and after the intervention using Enzyme‐linked immunosorbent assay (ELISA). Also, the levels of active caspase‐3 and caspase‐8 were detected in the PBMC by ELISA kit. Furthermore, we evaluated the efficacy of ASX on disease symptoms. Following the 8‐week intervention, ASX supplementation was able to reduce the expression of GRP78 (p = 0.051), CHOP (p = 0.008), XBP1 (p = 0.002), ATF4 (0.038), ATF6 (0.157) and DR5 (0.016) when compared to the placebo. However, this decrease was not statistically significant for ATF6 (p = 0.067) and marginally significant for GRP78 (p = 0.051). The levels of TNF‐α (p = 0.009), IL‐18 (p = 0.003), IL‐6 (p = 0.013) and active caspase‐3 (p = 0.012) were also statistically significant lower in the therapy group. However, there was no significant difference in CRP (p = 0.177) and caspase‐8 (p = 0.491) levels between the treatment and control groups. In our study, ASX had no significant positive effect on BMI, hirsutism, hair loss and regularity of the menstrual cycle. It appears that ASX may benefit PCOS by changing the ER stress‐apoptotic pathway and reducing serum inflammatory markers; however, additional research is required to determine this compound's potential relevance.

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Hyperandrogenism drives ovarian inflammation and pyroptosis: A possible pathogenesis of PCOS follicular dysplasia

Cited by 15 publications

References 68 publications

Therapeutic Effects of Pimpinella anisum Fruit Extract on Polycystic Ovary Syndrome in a Rat Model: Emerging Role of Inflammatory Responses and Oxidative Stress

Therapeutic Effects of Pimpinella anisum Fruit Extract on Polycystic Ovary Syndrome in a Rat Model: Emerging Role of Inflammatory Responses and Oxidative Stress

CISD2 regulates oxidative stress and mitophagy to maintain the balance of the follicular microenvironment in PCOS

Randomized clinical trial of astaxanthin supplement on serum inflammatory markers and ER stress‐apoptosis gene expression in PBMCs of women with PCOS

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