scholarly journals The Role of microRNAs in Ovarian Granulosa Cells in Health and Disease

2019 ◽  
Vol 10 ◽  
Author(s):  
Jiajie Tu ◽  
Albert Hoi-Hung Cheung ◽  
Clement Leung-Kwok Chan ◽  
Wai-Yee Chan
Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1770
Author(s):  
Guohua Song ◽  
Yixuan Jiang ◽  
Yaling Wang ◽  
Mingkun Song ◽  
Xuanmin Niu ◽  
...  

Cathepsin S (CTSS) is a member of cysteine protease family. Although many studies have demonstrated the vital role of CTSS in many physiological and pathological processes including tumor growth, angiogenesis and metastasis, the function of CTSS in the development of rabbit granulosa cells (GCS) remains unknown. To address this question, we isolated rabbit GCS and explored the regulatory function of the CTSS gene in cell proliferation and apoptosis. CTSS overexpression significantly promoted the secretion of progesterone (P4) and estrogen (E2) by increasing the expression of STAR and CYP19A1 (p < 0.05). We also found that overexpression of CTSS increased GCS proliferation by up-regulating the expression of proliferation related gene (PCNA) and anti-apoptotic gene (BCL2). Cell apoptosis was markedly decreased by CTSS activation (p < 0.05). In contrast, CTSS knockdown significantly decreased the secretion of P4 and E2 and the proliferation of rabbit GCS, while increasing the apoptosis of rabbit GCS. Taken together, our results highlight the important role of CTSS in regulating hormone secretion, cell proliferation, and apoptosis in rabbit GCS. These results might provide a basis for better understanding the molecular mechanism of rabbit reproduction.


Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 260 ◽  
Author(s):  
Xinling Wang ◽  
Chengmin Li ◽  
Yiru Wang ◽  
Lian Li ◽  
Zhaoyu Han ◽  
...  

Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) is an E3 ligase of ubiquitin fold modifier 1 (UFM1), which can act together with its target protein to inhibit the apoptosis of cells. Lipopolysaccharides (LPS) can affect the ovarian health of female animals by affecting the apoptosis of ovarian granulosa cells. The physiological function of UFL1 on the apoptosis of bovine (ovarian) granulosa cells (bGCs) remains unclear; therefore, we focused on the modulating effect of UFL1 on the regulation of LPS-induced apoptosis in ovarian granulosa cells. Our study found that UFL1 was expressed in both the nucleus and cytoplasm of bGCs. The results here demonstrated that LPS caused a significant increase in the apoptosis level of bGCs in cows, and also dramatically increased the expression of UFL1. Furthermore, we found that UFL1 depletion caused a significant increase in apoptosis (increased the expression of BAX/BCL-2 and the activity of caspase-3). Conversely, the overexpression of UFL1 relieved the LPS-induced apoptosis. In order to assess whether the inhibition of bGCs apoptosis involved in the nuclear factor-κB (NF-κB) signaling pathway resulted from UFL1, we detected the expression of NF-κB p-p65. LPS treatment resulted in a significant upregulation in the protein concentration of NF-κB p-p65, and knockdown of UFL1 further increased the phosphorylation of NF-κB p65, while UFL1 overexpression significantly inhibited the expression of NF-κB p-p65. Collectively, UFL1 could suppress LPS-induced apoptosis in cow ovarian granulosa cells, likely via the NF-κB pathway. These results identify a novel role of UFL1 in the modulation of bGC apoptosis, which may be a potential signaling target to improve the reproductive health of dairy cows.


2003 ◽  
Vol 284 (4) ◽  
pp. C880-C887 ◽  
Author(s):  
Joanne E. I. Gittens ◽  
Abdul Amir Mhawi ◽  
Darcy Lidington ◽  
Yves Ouellette ◽  
Gerald M. Kidder

Ovarian granulosa cells are coupled via gap junctions containing connexin43 (Cx43 or α-1 connexin). In the absence of Cx43, granulosa cells stop growing in an early preantral stage. However, the fact that granulosa cells of mature follicles express multiple connexins complicated interpretation of this finding. The present experiments were designed to clarify the role of Cx43 vs. these other connexins in the earliest stages of folliculogenesis. Dye injection experiments revealed that granulosa cells from Cx43 knockout follicles are not coupled, and this was confirmed by ionic current injections. Furthermore, electron microscopy revealed that gap junctions are extremely rare in mutant granulosa cells. In contrast, mutant granulosa cells were able to form gap junctions with wild-type granulosa cells in a dye preloading assay. It was concluded that mutant granulosa cells contain a population of connexons, composed of an unidentified connexin, that do not normally contribute to gap junctions. Therefore, although Cx43 is not the only gap junction protein present in granulosa cells of early preantral follicles, it is the only one that makes a significant contribution to intercellular coupling.


Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1418 ◽  
Author(s):  
Malgorzata Jozkowiak ◽  
Greg Hutchings ◽  
Maurycy Jankowski ◽  
Katarzyna Kulcenty ◽  
Paul Mozdziak ◽  
...  

Ovarian Granulosa Cells (GCs) are known to proliferate in the developing follicle and undergo several biochemical processes during folliculogenesis. They represent a multipotent cell population that has been differentiated to neuronal cells, chondrocytes, and osteoblasts in vitro. However, progression and maturation of GCs are accompanied by a reduction in their stemness. In the developing follicle, GCs communicate with the oocyte bidirectionally via gap junctions. Together with neighboring theca cells, they play a crucial role in steroidogenesis, particularly the production of estradiol, as well as progesterone following luteinization. Many signaling pathways are known to be important throughout the follicle development, leading either towards luteinization and release of the oocyte, or follicular atresia and apoptosis. These signaling pathways include cAMP, PI3K, SMAD, Hedgehog (HH), Hippo and Notch, which act together in a complex manner to control the maturation of GCs through regulation of key genes, from the primordial follicle to the luteal phase. Small molecules such as resveratrol, a phytoalexin found in grapes, peanuts and other dietary constituents, may be able to activate/inhibit these signaling pathways and thereby control physiological properties of GCs. This article reviews the current knowledge about granulosa stem cells, the signaling pathways driving their development and maturation, as well as biological activities of resveratrol and its properties as a pro-differentiation agent.


2018 ◽  
Vol 19 (7) ◽  
pp. 2028 ◽  
Author(s):  
Shujuan Wang ◽  
Wenju Liu ◽  
Xunsheng Pang ◽  
Sifa Dai ◽  
Guodong Liu

Ovarian granulosa cells (GCs) are a critical approach to investigate the mechanism of gene regulation during folliculogenesis. The objective of this study was to investigate the role of MT2 in bovine GCs, and assess whether MT2 silencing affected GCs response to melatonin. We found that MT2 silencing significantly decreased the secretion of progesterone and estradiol, and increased the concentration of inhibin B and activin B. To further reveal the regulatory mechanism of MT2 silencing on steroids synthesis, it was found that the expression of CYP19A1 and CYP11A1 enzymes (steroid hormone synthesis) were down-regulated, while genes related to hormonal synthesis (StAR, RUNX2, INHA and INHBB) were up-regulated without affecting the expression of INHBA, suggesting that MT2 silencing may regulate hormone abundance. Furthermore, MT2 silencing significantly increased the expression of TGFBR3 and BMP6, and decreased the expression of LHR and DNMT1A without significant difference in the expression of FSHR and EGFR. In addition, MT2 silencing didn’t affect the effect of melatonin on increasing the expression of DNMT1A, EGFR, INHBA and LHR, and progesterone level, or decreasing INHA, TGFBR3 and StAR expression, and production of inhibin B. Moreover, MT2 silencing could disrupt the role of melatonin in decreasing the FSHR, INHBB and BMP6 expression, and activin B secretion. In conclusion, these results reveal that melatonin and MT2 are essential regulator of bovine GCs function by modulating reproduction-related genes expression, hormones secretion and other regulators of folliculogenesis.


2021 ◽  
Author(s):  
Chengcai Wen ◽  
Li Zhang

Abstract Background Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive-aged women. This study was designed to explore the role of circ_0058063 in PCOS.Methods We recruited nine PCOS patients and nine no-PCOS patients. The concentrations of follicle stimulating hormone (FSH), testosterone (T), luteinizing hormone (LH), progesterone (P4) and estradiol (E2) were measured by radioimmunoassay. The level of aromatase was detected using an ELISA kit. The proliferation and apoptosis of ovarian granulosa cells were assessed using CCK-8 assay and flow cytometry, respectively. Gene and protein expression were evaluated through RT-qPCR and Western blotting assay.Results The circ_0058063 level in ovarian granulosa cells and follicular fluid is significantly higher in the PCOS group than the no-PCOS group. Besides, silencing circ_0058063 increases the levels of Aromatase mRNA, P4 and E2 in PCOS ovarian granulosa cells. Additionally, silencing circ_0058063 can promote the proliferation of ovarian granulosa cells in patients with PCOS. Furthermore, silencing circ_0058063 can suppress apoptosis of PCOS ovarian granulosa cells.Conclusions Silencing circ_0058063 enhances proliferation and inhibits apoptosis in PCOS ovarian granulosa cells. Such findings may offer vital insights into a therapeutic target for PCOS.


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