Ovarian Fibrosis

Zhou, Feng; Shi, Libing; Zhang, Songying

doi:10.4103/0366-6999.198931

Cited by 88 publications

(45 citation statements)

References 56 publications

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“…The low-grade chronic inflammatory condition favours overproliferation of fibroblasts, excessive ECM deposition, and fibrosis [36]. In accordance with a previous study using two different strains of mice [13], the current study displays a significant age-related increase of fibrosis around follicles, blood vessels, and in the ovarian stroma.…”

Section: Discussionsupporting

confidence: 88%

Apocynin Dietary Supplementation Delays Mouse Ovarian Ageing

Timóteo-Ferreira

Mendes

Rocha

et al. 2019

Oxidative Medicine and Cellular Longevity

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Advanced maternal age is associated with higher infertility rates, pregnancy-associated complications, and progeny health issues. The ovary is considered the main responsible for these consequences due to a continuous decay in follicle number and oocyte quality. Intracellular imbalance between oxidant molecules and antioxidant mechanisms, in favour of the former, results in oxidative stress (OS) that is believed to contribute to ovarian ageing. This work is aimed at evaluating whether an age-related increase in ovarian OS, inflammation, and fibrosis may contribute to tissue dysfunction and whether specific antioxidant supplementation with a NADPH oxidase inhibitor (apocynin) could ameliorate them. Mice aged 8–12 weeks (reproductively young) or 38-42 weeks (reproductively aged) were employed. Aged mice were divided into two groups, with one receiving apocynin (5 mM) in the drinking water, for 7 weeks, upon which animals were sacrificed and their ovaries collected. Ovarian structure was similar at both ages, but the ovaries from reproductively aged mice exhibited lipofuscin deposition, enhanced fibrosis, and a significant age-related reduction in primordial and primary follicle number when compared to younger animals. Protein carbonylation and nitration, and markers of OS were significantly increased with age. Moreover, mRNA levels of inflammation markers, collagens, metalloproteinases (MMPs), and tissue inhibitor MMPs (TIMPs) were upregulated. Expression of the antifibrotic miRNA29c-3p was significantly reduced. Apocynin supplementation ameliorated most of the age-related observed changes, sometimes to values similar to those observed in young females. These findings indicate that there is an age-related increase in OS that plays an important role in enhancing inflammation and collagen deposition, contributing to a decline in female fertility. Apocynin supplementation suggests that the imbalance can be ameliorated and thus delay ovarian ageing harmful effects.

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Section: Discussionsupporting

confidence: 88%

Apocynin Dietary Supplementation Delays Mouse Ovarian Ageing

Timóteo-Ferreira

Mendes

Rocha

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…In particular, levels of serum IL-6 increase with age in humans, and may mediate fibrosis by upregulating the expression of collagen, or by promoting cytokines that support collagen production 9 , 38 . The ovary undergoes a dramatic and periodic remodelling of extracellular matrix (ECM) as a consequence of cyclic follicle development and ovulation and this is part of normal ovarian function 39 . However, excessive deposition of ECM components and ovarian fibrosis have been associated with decreased follicle density and ovarian dysfunction in women with ovarian endometriosis cysts suggesting that there may be a link between follicle depletion and fibrosis 39 .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of inflammation and follicle depletion during ovarian ageing in mice

Lliberos

Liew

Zareie

et al. 2021

Sci Rep

131

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Reproductive ageing in females is defined by a progressive decline in follicle number and oocyte quality. This is a natural process that leads to the loss of fertility and ovarian function, cycle irregularity and eventually menopause or reproductive senescence. The factors that underlie the natural depletion of follicles throughout reproductive life are poorly characterised. It has been proposed that inflammatory processes and fibrosis might contribute to ovarian ageing. To further investigate this possibility, we evaluated key markers of inflammation and immune cell populations in the ovaries of 2, 6, 12 and 18-month-old C57BL/6 female mice. We report that the decrease in follicle numbers over the reproductive lifespan was associated with an increase in the intra-ovarian percentage of CD4 + T cells, B cells and macrophages. Serum concentration and intra-ovarian mRNA levels of several pro-inflammatory cytokines, including IL-1α/β, TNF-α, IL-6, and inflammasome genes ASC and NLRP3, were significantly increased with age. Fibrosis levels, as determined by picrosirius red staining for collagen I and III, were unchanged up to 18 months of age. Collectively, these data suggest that inflammation could be one of the mechanisms responsible for the age-related regulation of follicle number, but the role of fibrosis is unclear. Further studies are now required to determine if there is a causative relationship between inflammation and follicle depletion as females age.

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“…6 ). This caused accumulation of ECM, which promoted ovarian interstitial fibrosis by disrupting the balance between MMPs and TIMPs [ 33 ]. A few cystic follicles and a marginal accretion of ovarian granular cell layer were observed in ovaries of SB431542-exposed rat.…”

Section: Discussionmentioning

confidence: 99%

DHEA-induced ovarian hyperfibrosis is mediated by TGF-β signaling pathway

Wang

Qiao

et al. 2018

J Ovarian Res

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BackgroundThe polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder with pathological mechanisms remain unclear. The following study investigates the ovarian hyperfibrosis forming via transforming growth factor-β (TGF-β) signaling pathway in Dehydroepiandrosterone (DHEA)- induced polycystic ovary syndrome (PCOS) rat model. We furthermore explored whether TGF-βRI inhibitor (SB431542) decreases ovarian fibrosis by counterbalancing the expression of fibrotic biomarkers.MethodsThirty female Sprague-Dawley rats were randomly divided into Blank group (n = 6), Oil group (n = 6), and Oil + DHEA-induced model group (n = 6 + 12). The model groups were established by subcutaneous injection of DHEA for 35 consecutive days. The 12 successful model rats were additionally divided in vehicle group (n = 6) and SB431542-treated group (n = 6). Vehicle group and SB431542-treated group, served as administration group and were intraperitoneally injected with DMSO and SB431542 for additional 14 consecutive days. Ovarian morphology, fibrin and collagen localization and expression in ovaries were detected using H&E staining, immunohistochemistry and Sirius red staining. The ovarian protein and RNA were examined using Western blot and RT-PCR.ResultsIn DHEA-induced ovary in rat, fibrin and collagen had significantly higher levels, while the main fibrosis markers (TGF-β, CTGF, fibronectin, a-SMA) were obviously upregulated. SB431542 significantly reduced the expression of pro-fibrotic molecules (TGF-β, Smad3, Smad2, a-SMA) and increased anti-fibrotic factor MMP2.ConclusionTGF-βRI inhibitor (SB431542) inhibits the downstream signaling molecules of TGF-β and upregulates MMP2, which in turn prevent collagen deposition. Moreover, ovarian hyperfibrosis in DHEA-induced PCOS rat model could be improved by TGF-βRI inhibitor (SB431542) restraining the transcription of accelerating fibrosis genes and modulating EMT mediator.Electronic supplementary materialThe online version of this article (10.1186/s13048-017-0375-7) contains supplementary material, which is available to authorized users.

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Ovarian Fibrosis

Cited by 88 publications

References 56 publications

Apocynin Dietary Supplementation Delays Mouse Ovarian Ageing

Apocynin Dietary Supplementation Delays Mouse Ovarian Ageing

Evaluation of inflammation and follicle depletion during ovarian ageing in mice

DHEA-induced ovarian hyperfibrosis is mediated by TGF-β signaling pathway

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