Activation of TGF‐β1/Smad3 signaling pathway inhibits the development of ovarian follicle in polycystic ovary syndrome by promoting apoptosis of granulosa cells

Shen, Haoran; Wang, Yao

doi:10.1002/jcp.27854

Cited by 46 publications

(26 citation statements)

References 43 publications

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“…Previous reports indicate that the TGF‐β signaling pathway was playing a key role in proliferation, apoptosis, and autophagy of GC functions and follicular atresia (Du et al, 2016; Fang, Chang, Cheng, Leung, & Sun, 2014; J. Zhou et al, 2017). In mammals GCs, the TGF‐β signaling pathway may enhance GC proliferation and inhibit the development of ovarian follicle of PCOS by regulating the apoptosis of GCs (Du et al, 2016; Shen & Wang, 2019). Steroidogenesis and steroid hormones were related to follicle development (Fehrenbach, Nüsse, & Nayudu, 1998; Johnson, Solovieva, & Bridgham, 2012; Nozu et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

The circular RNA aplacirc_13267 upregulates duck granulosa cell apoptosis by the apla‐miR‐1‐13/THBS1 signaling pathway

Xiao

et al. 2020

Journal Cellular Physiology

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Follicle development is a key factor that determines the reproductive performance of poultry. The existing evidence suggests that circular RNAs (circRNAs) play an important role in a variety of biological processes, especially in posttranscriptional regulation, but the regulatory mechanism of circRNAs in duck follicle development has rarely been reported. To better explore the molecular mechanism of follicle development in ducks, we sequenced and analyzed the follicular circRNAs; 4,204 circRNAs were predicted in the duck follicles. Fourteen circRNAs were differentially expressed between the white follicles and yellow follicles. The results of our studies showed that aplacirc_013267 promoted cell apoptosis in duck GCs. Moreover, a bioinformatics prediction analysis demonstrated that aplacirc_013267 was involved in a circRNA‐miRNA‐mRNA coexpression network and was observed to sponge two follicle‐related miRNAs by a luciferase activity assay. Furthermore, we found that overexpression of aplacirc_013267 significantly increased thrombospondin‐1 (THBS1) expression and downregulated granulosa cell apoptosis. The mechanistic study showed that aplacirc_013267 directly binds to and inhibits apla‐mir‐1‐13; then, aplacirc_013267 increases the expression of THBS1 and upregulates granulosa cell apoptosis. Taken together, our findings demonstrate that circRNAs have potential effects in duck ovarian follicles and that circRNAs may represent a new avenue to understand follicular development.

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Section: Discussionmentioning

confidence: 99%

The circular RNA aplacirc_13267 upregulates duck granulosa cell apoptosis by the apla‐miR‐1‐13/THBS1 signaling pathway

Xiao

et al. 2020

Journal Cellular Physiology

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“…The in vitro experiments were conducted according to the protocol described previously [17,18]. The successfully modeled rats were injected (50 IU) pregnant mare serum gonadotropin (PMSG, hor-272, prospec) by injected intraperitoneally.…”

Section: Isolation Culture and Identi Cation Of Rat Ovarian Granulosmentioning

confidence: 99%

Protective Effects of Berberine on Rat Model of Polycystic Ovary Syndrome Through the PI3K/AKT Pathway

Ji¹,

Ding²,

Hua³

et al. 2020

Preprint

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Background: Berberine (Ber), a Chinese herbal monomer has been reported to exhibit an array of pharmacological activities relating to the lowering of blood glucose and the treatment of polycystic ovarian syndrome (PCOS). However, the related mechanism underlying these activites is not clear. In the current study, we aimed to elucidate the effect of Ber on rat model of PCOS by PI3K/AKT signaling pathway.Methods: A letrozole-induced rat PCOS model and primary ovarian granulosa cells model to explore the protective effect and the mechanism of action of Ber. In PCOS rats, the values of fasting blood glucose (FBG) insulin resistance (HOMA-IR), fasting insulin (FINS) values and the serum hormone levels were measured. The ovarian tissues were stained with HE and TUNEL to undergo pathological and apoptosis examination. Moreover, the effect of Ber on proliferation and apoptosis of granulosa cells was detected by CCK-8 and flow cytometry. And then the influence of Ber on granulosa cells was confirmed by blockade of the PI3K/AKT pathway. In addition, the modulatory effect on the expression of related proteins by blockade of PI3K/AKT was demonstrated via western blot.Results: We found that Ber was able to recover the serum hormone levels and improve insulin resistance (IR) in PCOS rat model. The morphological lesion and apoptosis of the ovary was also restored with the Ber treatment. Blockade of the PI3K/AKT pathway attenuated the influences of Ber on proliferation and apoptosis of granulosa cells. Due to this, we discovered a correlation between the PI3K/AKT signaling pathway and the beneficial effects of Ber, demonstrating that its application could alter the expression levels of key proteins in the PI3K/APT pathway.Conclusion: The beneficial effects of Ber on PCOS, including alter serum hormone levels, recover ovary morphological lesions, improve IR, improve cell viability and inhibition of apoptosis, which is mediated through the PI3K/AKT pathway.

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“…By binding to the receptor on the OGCs, a follicle-stimulating hormone induces the expression of cholesterol side-chain cleavage cytochrome P450 (CYP19A1) and 17 β -hydroxysteroid dehydrogenase (CYP17A1) which are rate-limiting enzymes to catalyze conversion from estrogen to estradiol [ 6 ]. Apoptosis of OGCs leads to the deficiency of estradiol and blocks the follicle development and maturation, ultimately forming more numbers of hypogenetic secondary follicles undergoing atresia and antral follicles [ 7 ]. Therefore, exploration of molecular mechanisms associated with the apoptosis of OGCs may provide underlying targets for developing drugs.…”

Section: Introductionmentioning

confidence: 99%

Identification of Crucial lncRNAs, miRNAs, mRNAs, and Potential Therapeutic Compounds for Polycystic Ovary Syndrome by Bioinformatics Analysis

Zeng

Lin

Xia

et al. 2020

BioMed Research International

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Background. This study was aimed at mining crucial long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) for the development of polycystic ovary syndrome (PCOS) based on the coexpression and the competitive endogenous RNA (ceRNA) theories and investigating the underlying therapeutic drugs that may function by reversing the expression of lncRNAs, miRNAs, and mRNAs. Methods. RNA (GSE106724, GSE114419, GSE137684, and GSE138518) or miRNA (GSE84376 and GSE138572) expression profile datasets of PCOS patients were downloaded from the Gene Expression Omnibus database. The weighted gene coexpression network analysis (WGCNA) using four RNA datasets was conducted to construct the lncRNA-mRNA coexpression networks, while the common differentially expressed miRNAs in two miRNA datasets and module RNAs were used to establish the ceRNA network. A protein-protein interaction (PPI) network was created to explore the potential interactions between genes. Gene Ontology and KEGG pathway enrichment analyses were performed to explore the functions of genes in networks. Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD) analyses were performed to identify potential therapeutic agents for PCOS. Results. Three modules (black, magenta, and yellow) were identified to be PCOS-related after WGCNA analysis, in which KLF3-AS1-PLCG2, MAPKAPK5-AS1-MAP3K14, and WWC2-AS2-TXNIP were important coexpression relationship pairs. WWC2-AS2-hsa-miR-382-PLCG2 was a crucial ceRNA loop in the ceRNA network. The PPI network showed that MAP3K14 and TXNIP could interact with hub genes PLK1 ( degree = 21 ) and TLR1 ( degree = 18 ), respectively. These genes were enriched into mitosis (PLK1), immune response (PLCG2 and TLR1), and cell cycle (TXNIP and PLK1) biological processes. Ten small molecule drugs (especially quercetin) were considered to be therapeutical for PCOS. Conclusion. Our study may provide a novel insight into the mechanisms and therapy for PCOS.

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Activation of TGF‐β1/Smad3 signaling pathway inhibits the development of ovarian follicle in polycystic ovary syndrome by promoting apoptosis of granulosa cells

Cited by 46 publications

References 43 publications

The circular RNA aplacirc_13267 upregulates duck granulosa cell apoptosis by the apla‐miR‐1‐13/THBS1 signaling pathway

The circular RNA aplacirc_13267 upregulates duck granulosa cell apoptosis by the apla‐miR‐1‐13/THBS1 signaling pathway

Protective Effects of Berberine on Rat Model of Polycystic Ovary Syndrome Through the PI3K/AKT Pathway

Identification of Crucial lncRNAs, miRNAs, mRNAs, and Potential Therapeutic Compounds for Polycystic Ovary Syndrome by Bioinformatics Analysis

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