Circulating microRNAs in follicular fluid, powerful tools to explore in vitro fertilization process

Scalici, E.; Traver, Sabine; Mullet, T.; Molinari, Nicolas; Ferrières, A.; Brunet, C.; Belloc, S.; Hamamah, S.

doi:10.1038/srep24976

Cited by 82 publications

(68 citation statements)

References 57 publications

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“…In recent years, miR-140 has been reported to exhibit significant regulatory effects with respect to cell proliferation, differentiation, migration, and invasion [11][12][13]. Scalici et al showed that the expression of miR-140 in the follicular fluid was different between PCOS and normal ovarian reserves, with a specificity of 83.8% and a sensitivity of 70% [14]. However, the expression profile of miR-140-along with its underlying mechanism during ovarian dysfunction-is still poorly reported.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: MiR-140 targets RAP2A to enable the proliferation of insulin-treated ovarian granulosa cells

Xiong

Wang

et al. 2020

J Ovarian Res

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Background: We elucidated the role of specific MicroRNAs (miRNAs) in the development of polycystic ovary syndrome (PCOS) and explained the changes in the proliferation of granulosa cells. Excised ovarian cortex specimens were collected for miRNA profiling analysis (n = 20 PCOS females and 5 non-PCOS females). Insulintreated ovarian granulosa cells isolated from mice were used for mechanical studies. Results: High miR-140 expression was observed in PCOS samples and insulin-treated granulosa cells compared to that in non-PCOS and unstimulated cells, respectively. However, the Ras-related protein Rap-2a precursor (RAP2A) was downregulated in in PCOS. MTT assay and EdU staining showed that an miR-140 inhibitor attenuated viability in insulin-treated granulosa cells; cell viability increased with miR-140 overexpression. Reduced expression of miR-140 and the expression of the miR-140 mimic resulted in marked cell apoptosis, as evidenced by the results of PI flow cytometry and Annexin V-FITC; miR-140 overexpression results in downregulated RAP2A expression, and the miR-140 mimic directly bound to the RAP2A 3′-UTR, causing increase in RAP2A levels in insulin-treated granulosa cells; RNA-mediated silencing of RAP2A in insulin-treated granulosa cells restored cell proliferation and apoptosis to normal levels. Phosphorylated AKT was found to be negatively regulated through cross-talk between miR-140 and RAP2A. Conclusions: In conclusion, PCOS ovarian cortex specimens and insulin-treated granulosa cells showed elevated expression of miR-140, which could lead to increased proliferation and reduced apoptosis of cells by targeting RAP2A. This study may pave the way for future research on the properties of granulosa cells in PCOS.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: MiR-140 targets RAP2A to enable the proliferation of insulin-treated ovarian granulosa cells

Xiong

Wang

et al. 2020

J Ovarian Res

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“…Of the 28 articles included, 18 evaluated the miRNAs in ovaries and/or extracellular vesicles (i.e., exosomes and microvesicles) [9,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]; three in oocytes [33][34][35]; and seven in embryos [36][37][38][39][40][41][42].…”

Section: Summary Of Selected Studiesmentioning

confidence: 99%

“…The other four articles explored a small number of miRNAs in PCOS patients, all using qRT-PCR. One of these studies compared the expression of five miRNAs in the follicular fluid between 30 women with PCOS and 91 women with normal ovarian reserve (NOR; as controls), and found that miR-30a was significantly up-regulated and miR-140 and let-7b were significantly down-regulated in the follicular fluid from patients with PCOS compared with women with NOR [18]. Another work investigated, by comparing women suffering from PCOS (n = 25) with women without PCOS (n = 20), the effects of miR-145 on cell proliferation and its underlying mechanism in isolated human granulosa cells from aspirated follicular fluid.…”

Section: /14mentioning

confidence: 99%

The Expression of miRNAs in Human Ovaries, Oocytes, Extracellular Vesicles, and Early Embryos: A Systematic Review

Salas‐Huetos

James

Aston

et al. 2019

Cells

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The recent discovery of microRNAs (miRNAs) in human reproductive tissues and cells indicates a possible functional role in reproductive function. However, the studies published to date in female reproductive tissues/cells and embryos are inconclusive and sometimes controversial. In order to update the knowledge of this field, the present study aimed to discuss, through a systematic review, the role of miRNAs in female human reproduction and early embryogenesis. We conducted a systematic review of the published literature in MEDLINE and EMBASE databases through June 2018 (plus a complementary search until July 2019), in accordance with the PRISMA guidelines. We have included descriptive and observational studies, in which fertile/infertile women were well-defined. The primary outcome was the miRNA expression in ovaries, oocytes, extracellular vesicles, and embryos. We identified 25,204 articles, of which 28 were selected for qualitative analysis: 18 in ovaries and extracellular vesicles, three in oocytes, and seven in embryos. The present systematic review of descriptive and observational studies demonstrates that aberrant miRNA expression in female reproductive tissues/cells and embryos is related with infertility and embryogenesis errors. The expression of specific miRNAs, particularly in extracellular vesicles, may be used in the future as biomarkers of infertility and prognostic tools of embryo development.

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“…Sang et al first reported that the supernatant, microvesicles or exosomes from cell-free human follicular fluid contain miRNAs, which are important in metabolic and reproductive signaling pathways (Sang et al 2013). Moreover, the miRNAs in human follicular fluid are powerful tools in the in vitro fertilization (IVF) process, which can predict the development of expanded blastocysts and clinical pregnancy outcome (Scalici et al 2016). However, there have been few studies concerning the relationship between miRNAs in human follicular fluid and the pathogenesis of PCOS.…”

Section: Introductionmentioning

confidence: 99%

miRNA-335-5p negatively regulates granulosa cell proliferation via SGK3 in PCOS

Yao

et al. 2018

Reproduction

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Polycystic ovary syndrome (PCOS) is a major cause of infertility in women of reproductive age. However, its exact etiology remains unknown. In this study, we sequenced miRNAs in human follicular fluid and identified 16 downregulated and 3 upregulated miRNAs in PCOS group compared with non-PCOS group. Among the differential expressed miRNAs, miR-335-5p was verified lower abundance in PCOS than non-PCOS group using quantitative real-time PCR. Besides, miR-335-5p negatively correlated with antral follicle count, anti-Müllerian hormone and total testosterone. Bioinformatics analysis identified serum/glucocorticoid-regulated kinase family member 3 (SGK3) as a potential target gene of miR-335-5p. SGK3 is involved in protein kinase B-mammalian target of rapamycin kinase (AKT-mTOR) signaling pathway and cell proliferation. Western blotting and cell counting kit-8 assays demonstrated that miR-335-5p mimic reduced, while miR-335-5p inhibitor increased, SGK3 abundance, AKT-mTOR pathway and cell proliferation in human granulosa-like tumor KGN cells. Dual-luciferase reporter assays showed that miR-335-5p binds to the 3′ untranslated region of SGK3 mRNA. Furthermore, miR-335-5p was decreased and SGK3 was elevated in human granulosa cells obtained from PCOS patients as compared with non-PCOS controls. These findings suggested that miR-335-5p is involved in granulosa cells proliferation by reducing SGK3 expression, which might provide a molecular target to improve dysfunctional granulosa cells in patients with PCOS.

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Circulating microRNAs in follicular fluid, powerful tools to explore in vitro fertilization process

Cited by 82 publications

References 57 publications

RETRACTED ARTICLE: MiR-140 targets RAP2A to enable the proliferation of insulin-treated ovarian granulosa cells

RETRACTED ARTICLE: MiR-140 targets RAP2A to enable the proliferation of insulin-treated ovarian granulosa cells

The Expression of miRNAs in Human Ovaries, Oocytes, Extracellular Vesicles, and Early Embryos: A Systematic Review

miRNA-335-5p negatively regulates granulosa cell proliferation via SGK3 in PCOS

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