miR-21-3p inhibits autophagy of bovine granulosa cells by targeting VEGFA via PI3K/AKT signaling

Ma, Lizhu; Zheng, Yuxin; Tang, Xiaorong; Gao, Hong; Liu, Ning; Gao, Yan; Hao, Lizhuang; Liu, Shujie; Jiang, Zhongliang

doi:10.1530/rep-19-0285

Cited by 37 publications

(41 citation statements)

References 34 publications

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“…Here, we demonstrated that autophagy and apoptosis occur in GCs in different stages of follicles and autophagy mainly occurs in GCs of medium follicles, while apoptosis mainly occurs in GCs of large follicles. However, autophagy was found in bovine granulosa cells of large follicles, while apoptosis was found in medium follicles [19]. These results showed variation between species.…”

Section: Discussionmentioning

confidence: 81%

Autophagy and Apoptosis of Porcine Ovarian Granulosa Cells During Follicular Development

Zheng

Liu

et al. 2019

Animals

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Follicular atresia is closely related to both apoptosis and autophagy of granulosa cells (GCs) in ovarian follicles. In the present study, GCs were isolated from pig ovaries in small, medium and large antral follicles, and the current results showed that the proliferation of GCs was higher in medium follicles, and lower in large follicles compared to small follicles. The Bax and Caspase 3 mRNA levels were significantly higher, but the ratio of Bcl-2/Bax was lower in GCs of large follicles. The marker genes of autophagy, Atg3, Atg7 and LC3 mRNA levels were higher in GCs from medium follicles. Apoptosis- and autophagy-related proteins had a similar expression pattern to the mRNA level. Our results showed that phosphorylated ERK (p-ERK) was activated in GCs of large follicles, while phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR) were inhibited in GCs of medium follicles. Labeling of autophagic vesicles with 4’,6-diamidino-2-phenylindole (DAPI) and monodansylcadaverine (MDC) confirmed the results of gene transcription and protein expression in GCs of different size follicles. We conclude that autophagy and apoptosis of GCs occurred in different size follicles during follicular development, and autophagy was mainly found in GCs of medium follicles, while apoptosis was mainly found in GCs of large follicles.

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Section: Discussionmentioning

confidence: 81%

Autophagy and Apoptosis of Porcine Ovarian Granulosa Cells During Follicular Development

Zheng

Liu

et al. 2019

Animals

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“…Similarly, overexpression or knockdown studies using lentiviral transduction in bovine cumulus cells have shown that miRNAs such as miR-375 could affect oocyte maturation by targeting ADAM metallopeptidase with thrombospondin type 1 motif 1 (ADAMTS1) and progesterone receptor (PGR) genes [51]. Moreover, inhibitory role of miR-21-3p in utophagy, which determines the fate of granulosa cells, in bovine granulosa cells by targeting VEGFA via PI3K/AKT signaling has been documented [52]. Apart from these, in vitro functional studies have demonstrated that several miRNAs including miR-146a, miR-183-96-182 cluster, miR-383 and others are believed to regulate folliculogenesis or oocyte maturation by maintaining the survival and proliferation of granulosa/cumulus cells functions (Table 1).…”

Section: Functional Analysis Of Mirnas In Oocyte Companion Somatic Cellsmentioning

confidence: 98%

The Role of MicroRNAs in Mammalian Fertility: From Gametogenesis to Embryo Implantation

Salilew‐Wondim

Gebremedhn

Hoelker

et al. 2020

IJMS

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The genetic codes inscribed during two key developmental processes, namely gametogenesis and embryogenesis, are believed to determine subsequent development and survival of adult life. Once the embryo is formed, its further development mainly depends on its intrinsic characteristics, maternal environment (the endometrial receptivity), and the embryo–maternal interactions established during each phase of development. These developmental processes are under strict genetic regulation that could be manifested temporally and spatially depending on the physiological and developmental status of the cell. MicroRNAs (miRNAs), one of the small non-coding classes of RNAs, approximately 19–22 nucleotides in length, are one of the candidates for post-transcriptional developmental regulators. These tiny non-coding RNAs are expressed in ovarian tissue, granulosa cells, testis, oocytes, follicular fluid, and embryos and are implicated in diverse biological processes such as cell-to-cell communication. Moreover, accumulated evidences have also highlighted that miRNAs can be released into the extracellular environment through different mechanisms facilitating intercellular communication. Therefore, understanding miRNAs mediated regulatory mechanisms during gametogenesis and embryogenesis provides further insights about the molecular mechanisms underlying oocyte/sperm formation, early embryo development, and implantation. Thus, this review highlights the role of miRNAs in mammalian gametogenesis and embryogenesis and summarizes recent findings about miRNA-mediated post-transcriptional regulatory mechanisms occurring during early mammalian development.

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“…Moreover, autophagy of granulosa cells is suppressed by activation of the mTOR signalling pathway mediated by AKT during follicular atresia [15]. In our lab, thea previous study indicateds that BGC autophagy is involved in follicular atresia [3,4]. Although studies have elucidated the function of GC autophagy in follicular atresia and ovarian primordial follicular reserves [16], the regulatoryion mechanism of autophagy in GC is indistinct.…”

Section: Disscussionmentioning

confidence: 83%

Estrogen receptor β (ERβ) induces bovine ovarian granulosa cell (BGC) autophagy via the AKT/mTOR pathway

Zheng¹,

Liu²,

Tang³

et al. 2020

Asian-Australas J Anim Sci

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The aim of our study was to determine thatwhether ERβ regulates cell s proliferation, steroidogenesis, autophagy and signalingsignalling pathways in bovine ovarian granulosa cells in vitro. Methods: In this study, bovine ovarian granulosa cells (BGCs) were cultured and transfected with ERβ siRNA (si-ERβ) or overexpressiona plasmid overexpressing ERβ (oe-ERβ), and CCK-8 kit was used to detectassess the cell proliferation. , Rreal-time PCR was used to measure the genesgene transcription. Western-blot blotting was used to determinemeasure proteins expression, and a specific kit was used to measure the production of steroid hormones. Results: The results showed the ERβ onaffects BGC proliferation for the first time according to the gene transcription levels of FSHR, CYP19A1, HSD3β1 and STAR, and onthe production of E2 and P4. ERβ was identified as an important nuclear receptor that induced BGC autophagy based on the mRNA and protein expression ofon the current results autophagy-related genes mRNA level and protein expression. MeanwhileFurthermore, the role of ERβ onin BGC autophagy was confirmed through the treatment ofwith rapamycin (RAPA) or 3-methyladenine (3-MA) onin BGCs by co-transfection with si-ERβ or oe-ERβ in BGCs, respectively. The results ofrelated to AKT/mTOR signalling and its phosphorylation suggested that ERβ induces BGC A c c e p t e d A r t i c l e autophagy through attenuating AKT/mTOR signalling. In summary, this study demonstrates that ERβ regulates BGC proliferation and function, and induces BGC autophagy by targeting AKT/mTOR signalling. Conclusion: These data reveals a novel regulatory mechanism of autophagy via ERβ and provide insights into the role of autophagy in BGCs.

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miR-21-3p inhibits autophagy of bovine granulosa cells by targeting VEGFA via PI3K/AKT signaling

Cited by 37 publications

References 34 publications

Autophagy and Apoptosis of Porcine Ovarian Granulosa Cells During Follicular Development

Autophagy and Apoptosis of Porcine Ovarian Granulosa Cells During Follicular Development

The Role of MicroRNAs in Mammalian Fertility: From Gametogenesis to Embryo Implantation

Estrogen receptor β (ERβ) induces bovine ovarian granulosa cell (BGC) autophagy via the AKT/mTOR pathway

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