scholarly journals Chromatin Accessibility and Transcriptomic Alterations in Murine Ovarian Granulosa Cells Upon Deoxynivalenol Exposure

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2818
Author(s):  
Hairui Fan ◽  
Zhanshi Ren ◽  
Chao Xu ◽  
Haifei Wang ◽  
Zhengchang Wu ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Sulfur Metabolism ◽  
Hormone Secretion ◽  
Underlying Mechanism ◽  
Regulatory Elements ◽  
Mapk Signaling ◽  
Chromatin Accessibility ◽  
Ovarian Granulosa Cells ◽  
Vitro Model

Deoxynivalenol (DON) is a common environmental toxin that is secreted by fusarium fungi that frequently contaminates feedstuff and food. While the detrimental effects of DON on human and animal reproductive systems have been well recognized, the underlying mechanism remains poorly understood. Ovarian granulosa cells (GCs), which surround oocytes, are crucial for regulating oocyte development, mainly through the secretion of hormones such as estrogen and progesterone. Using an in vitro model of murine GCs, we characterized the cytotoxic effects of DON and profiled genome-wide chromatin accessibility and transcriptomic alterations after DON exposure. Our results suggest that DON can induce decreased viability and growth, increased apoptosis rate, and disrupted hormone secretion. In total, 2533 differentially accessible loci and 2675 differentially expressed genes were identified that were associated with Hippo, Wnt, steroid biosynthesis, sulfur metabolism, and inflammation-related pathways. DON-induced genes usually have a concurrently increased occupancy of active histone modifications H3K4me3 and H3K27ac in their promoters. Integrative analyses identified 35 putative directly affected genes including Adrb2 and Fshr, which are key regulators of follicular growth, and revealed that regions with increased chromatin accessibility are enriched with the binding motifs for NR5A1 and NR5A2, which are important for GCs. Moreover, DON-induced inflammatory response is due to the activation of the NF-κB and MAPK signaling pathways. Overall, our results provide novel insights into the regulatory elements, genes, and key pathways underlying the response of ovarian GCs to DON cytotoxicity.

scholarly journals Tri-ortho-cresyl phosphate induces autophagy of mouse ovarian granulosa cells

Reproduction ◽  
2019 ◽  
Vol 158 (1) ◽  
pp. 61-69 ◽  
Author(s):  
Jinglei Wang ◽  
Wenli Ruan ◽  
Boshu Huang ◽  
Shuxin Shao ◽  
Dan Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Granulosa Cells ◽  
Flame Retardants ◽  
Underlying Mechanism ◽  
Serum Estradiol ◽  
Female Reproductive System ◽  
Ovarian Granulosa Cells ◽  
Viable Cells ◽  
Transmission Electron

Tri-ortho-cresyl phosphate (TOCP) has been widely used as plasticizers, plastic softeners and flame-retardants in industry and reported to have male reproductive toxicology. However, it is still unknown whether TOCP affects the female reproductive system and its underlying mechanism. In the present study, we found that TOCP exposure significantly decreased ovarian coefficient, caused disintegration and depletion of the granulosa cells in the ovary tissue and significantly inhibited the level of serum estradiol (E2). TOCP markedly increased both LC3-II and the ratio of LC3-II/LC3-I as well as autophagy proteins ATG5 and Beclin1 in the ovary tissue, implying that TOCP could induce autophagy in the ovary tissue. To further investigate the potential mechanism, primary ovarian granulosa cells were isolated in vitro and treated with 0–0.5 mM TOCP for 48 h. We showed that TOCP decreased the number of viable mouse granulosa cells without affecting cell cycle and apoptosis of the cells. Intriguingly, TOCP treatment markedly increased both LC3-II and the ratio of LC3-II/LC3-I as well as ATG5 and Beclin1. Furthermore, transmission electron microscopy (TEM) showed that autophagic vesicles in the cytoplasm increased significantly in the TOCP-treated cells, indicating that TOCP could induce autophagy in the cells. Taken together, TOCP reduces the number of viable cells and induces autophagy in mouse ovarian granulosa cells without affecting cell cycle and apoptosis.

Effects of selected nanoparticles on in vitro steroid hormone secretion by porcine ovarian granulosa cells

2013 ◽  
Vol 41 ◽  
pp. 33-34 ◽  
Author(s):  
Sona Scsukova ◽  
Alzbeta Mlynarcikova ◽  
Kvetoslava Smolikova ◽  
Eva Rollerova
Keyword(s):  
Granulosa Cells ◽  
Steroid Hormone ◽  
Hormone Secretion ◽  
Ovarian Granulosa Cells

scholarly journals Arachidonic Acid Regulation of Intracellular Signaling Pathways and Target Gene Expression in Bovine Ovarian Granulosa Cells

Animals ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 374 ◽  
Author(s):  
Nina Zhang ◽  
Liqiang Wang ◽  
Guoya Luo ◽  
Xiaorong Tang ◽  
Lizhu Ma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Granulosa Cells ◽  
Intracellular Signaling ◽  
Hormone Secretion ◽  
Ovarian Granulosa Cells ◽  
Genes Expression ◽  
Higher Doses ◽  
Gene Expression Levels

In the present study, AA was used to challenge bovine ovarian granulosa cells in vitro and the related parameters of cellular and molecular biology were measured. The results indicated that lower doses of AA increased survival of bovine granulosa cells whereas higher doses of AA suppressed survival. While lower doses of AA induced accumulation of lipid droplet in granulosa cells, the higher dose of AA inhibited lipid accumulation, and AA increased abundance of FABP3, CD36 and SLC27A1 mRNA. Higher doses of AA decreased the secretion of E2 and increased the secretion of P4 accompanied by down-regulation of the mRNA abundance of CYP19A1, FSHR, HSD3B1 and STAR in granulosa cells. The signaling pathways employed by AA in the stimulation of genes expression included both ERK1/2 and Akt. Together, AA specifically affects physiological features, gene expression levels and steroid hormone secretion, and thus altering the functionality of granulosa cells of cattle.

scholarly journals Stimulatory effect of amygdalin on the viability and steroid hormone secretion by porcine ovarian granulosa cells in vitro

2016 ◽  
Vol 05 (Special issue 1) ◽  
pp. 44-46 ◽  
Author(s):  
Marek Halenár ◽  
Eva Tušimová ◽  
Anna Nynca ◽  
Agnieszka Sadowska ◽  
Renata Ciereszko ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Steroid Hormone ◽  
Hormone Secretion ◽  
Ovarian Granulosa Cells

scholarly journals Modulation of Cathepsin S (CTSS) Regulates the Secretion of Progesterone and Estradiol, Proliferation, and Apoptosis of Ovarian Granulosa Cells in Rabbits

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1770
Author(s):  
Guohua Song ◽  
Yixuan Jiang ◽  
Yaling Wang ◽  
Mingkun Song ◽  
Xuanmin Niu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cells ◽  
Hormone Secretion ◽  
Vital Role ◽  
Regulatory Function ◽  
Cathepsin S ◽  
Related Gene ◽  
Ovarian Granulosa Cells ◽  
Proliferation And Apoptosis

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.

scholarly journals Serum deprivation affects secretory activity of cultured porcine ovarian follicles and granulosa cells and their response to hormones

2009 ◽  
Vol 54 (No. 10) ◽  
pp. 455-460
Author(s):  
A.V. Sirotkin
Keyword(s):  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Secretory Activity ◽  
Ovarian Follicles ◽  
Serum Deprivation ◽  
Ovarian Cells ◽  
Igf I ◽  
Granulose Cells ◽  
Vitro Model

The aim of the present study is to understand the hormonal mechanisms of the effect of malnutrition on ovarian follicle functions. For this purpose, we examined the effect of malnutrition/serum deprivation, addition of metabolic hormones and gonadotropin (IGF-I, leptin and FSH) and their combination on the release of progesterone (P<sub>4</sub>), testosterone (T), estradiol (E<sub>2</sub>) and insulin-like growth factor I (IGF-I) by cultured whole ovarian follicles and on P<sub>4</sub> and IGF-I output by cultured granulosa cells isolated from porcine ovaries. It was observed that in ovarian follicles cultured with nutrients/serum addition of IGF-I reduced release of P<sub>4</sub>, but not of T or E<sub>2</sub>. Exogenous leptin reduced output of E<sub>2</sub>, but not of P<sub>4</sub> or T, and increased IGF-I output. No significant effect of FSH on release of steroid hormones by isolated follicles was found. Serum deprivation did not affect release of P<sub>4</sub>, but reduced output of T and E<sub>2</sub>, and promoted IGF-I release by cultured ovarian follicles. Addition of hormones failed to prevent the effect of malnutrition on the secretory activity of cultured ovarian follicles. In cultured granulose cells, all the tested hormones promoted release of both P<sub>4</sub> and IGF-I. Food restriction/serum deprivation reduced both P<sub>4</sub> and IGF-I output. Additions of either IGF-I, leptin and FSH prevented the inhibitory action of malnutrition on both P<sub>4</sub> and IGF-I release. The present observations (1) confirm the involvement of the hormones IGF-I, leptin and FSH in the control of secretory activity of ovarian cells, (2) demonstrate, that both isolated ovarian granulosa cells and whole follicles cultured in the absence of serum nutrients could be an adequate in-vitro model for studying the effect of malnutrition on ovarian secretory functions, and (3) suggest, that malnutrition could affect ovarian functions through changes in the release of ovarian hormones.

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