scholarly journals Cyclophosphamide-Induced Apoptosis in COV434 Human Granulosa Cells Involves Oxidative Stress and Glutathione Depletion

2007 ◽  
Vol 98 (1) ◽  
pp. 216-230 ◽  
Author(s):  
M. Tsai-Turton ◽  
B. T. Luong ◽  
Y. Tan ◽  
U. Luderer
Keyword(s):  
Oxidative Stress ◽  
Granulosa Cells ◽  
Glutathione Depletion ◽  
Human Granulosa Cells ◽  
Induced Apoptosis

P–229 Oxidative stress and Metformin; an in-vitro study on serum and primary human granulosa cell cultures

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F Alam ◽  
R Rehman ◽  
N Farooqui ◽  
F Jehan ◽  
S H Abidi
Keyword(s):  
Oxidative Stress ◽  
Sample Size ◽  
Granulosa Cell ◽  
Cell Cultures ◽  
Granulosa Cells ◽  
Metformin Treatment ◽  
Serum Samples ◽  
Human Granulosa Cells ◽  
Human Granulosa Cell ◽  
Infertile Patients

Abstract Study question What is the effect of administration of Metformin on the oxidative stress (OS) levels in serum and primary human granulosa cell cultures of infertile females? Summary answer Metformin suppresses oxidative stress in serum and human granulosa cells and increases the expression of SIRT1 in OS induced environment. What is known already Oxidative stress (OS) is a resultant of mitochondrial dysfunction when it either fails to fight against the oxidants or the expression of the antioxidants is not sufficient. Cellular damage including DNA damage is a common resultant of oxidative stress. OS effects the oocyte maturation and moreover, the cleavage phase in the early embryonic stage. The raised levels of OS makers are hypothesized to compromise the nuclear maturation and the mitotic spindles of the maturing oocytes. Metformin seemed to decrease oxidative stress and improve insulin resistance, dyslipidaemia and endothelial dysfunction in PCOS patients Study design, size, duration This cross-sectional study was conducted from August 2017 – July 2019, at Aga Khan Hospital in collaboration with Australian Concept Infertility Medical Centre (ACIMC) on ten infertile patients undergoing egg retrieval after ethical approval from of Aga Khan Hospital (AKU-ERC–2018–0557–601). Participants/materials, setting, methods Serum samples were obtained and analysed. Follicular fluid of these subjects was collected for establishment of primary cell culture model of normal human granulosa cells (hGCs). Serum and hGC cultures were grouped as; a) control: treatment, b) Test1: H2O2 induced OS, and c) Test2: H2O2 induced OS treated with metformin. OS was estimated in all groups by Mishra method. The two Test groups were assessed for SIRT1 levels using quantitative PCR employing SIRT1 specific primers Main results and the role of chance With mean age of 32.04 ± 2.29 years the mean BMI was 27.61 ± 2.15 kg/m2. OS was induced and measured by an increase in optical density (OD) in hGC Test samples which showed 0.28 (0.16–0.40) OD when compared with control hGC samples 0.153 (0.09–0.23). There was a significant reduction in ODs after metformin treatment in the stress induced cells 0.182 (0.05–0.30). A similar pattern was observed in the serum samples in ODs; control: 0.105 (0.09–0.15), stress induced samples: 0.199 (0.19–0.20). and stress induced serum sample with metformin treatment: 0.1415 (0.06–0.18). The Ct values obtained to express the effect of metformin on SIRT1 levels, for OS induced (Test1) and OS induced metformin treated (Test2) cells were found to be 29.12 and 26.42, respectively. We also observed a significant (85%) difference in the fold change of SIRT1 expression between metformin treated and untreated cells. Limitations, reasons for caution Small sample size is the limitation of this study. The impact of metformin on cell cultures due to different causes of infertility could not be ascertained Wider implications of the findings: Metformin suppresses oxidative stress in serum and human granulosa cells and increases the expression of SIRT1 in OS induced environment, therefore, metformin may be considered as a treatment of oxidative stress in infertile patients. Randomized control trial with large sample size is recommended to confirm the cause and effect relationship. Trial registration number Not applicable

Encircling granulosa cells protects against di-(2-ethylhexyl)phthalate-induced apoptosis in rat oocytes cultured in vitro

Zygote ◽  
2019 ◽  
Vol 27 (4) ◽  
pp. 203-213 ◽  
Author(s):  
Anima Tripathi ◽  
Vivek Pandey ◽  
A.N. Sahu ◽  
Alok K. Singh ◽  
Pawan K. Dubey
Keyword(s):  
Oxidative Stress ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Granulosa Cells ◽  
Mitochondrial Membrane ◽  
Dependent Manner ◽  
Apoptotic Markers ◽  
Induced Apoptosis ◽  
Ethylhexyl Phthalate

SummaryThe present study investigated if the presence of encircling granulosa cells protected against di(2-ethylhexyl)phthalate (DEHP)-induced oxidative stress in rat oocytes cultured in vitro. Denuded oocytes and cumulus–oocyte complexes (COCs) were treated with or without various doses of DEHP (0.0, 25.0, 50.0, 100, 200, 400 and 800 μM) in vitro. Morphological apoptotic changes, levels of oxidative stress and reactive oxygen species (ROS), mitochondrial membrane potential, and expression levels of apoptotic markers (Bcl2, Bax, cytochrome c) were analyzed. Our results showed that DEHP induced morphological apoptotic changes in a dose-dependent manner in denuded oocytes cultured in vitro. The effective dose of DEHP (400 µg) significantly (P>0.05) increased oxidative stress by elevating ROS levels and the mitochondrial membrane potential with higher mRNA expression and protein levels of apoptotic markers (Bax, cytochrome c). Encircling granulosa cells protected oocytes from DEHP-induced morphological changes, increased oxidative stress and ROS levels, as well as increased expression of apoptotic markers. Taken together our data suggested that encircling granulosa cells protected oocytes against DEHP-induced apoptosis and that the presence of granulosa cells could act positively towards the survival of oocytes under in vitro culture conditions and may be helpful during assisted reproductive technique programmes.

Presence of encircling granulosa cells protects against oxidative stress-induced apoptosis in rat eggs cultured in vitro

APOPTOSIS ◽  
2016 ◽  
Vol 22 (1) ◽  
pp. 98-107 ◽  
Author(s):  
Meenakshi Tiwari ◽  
Anima Tripathi ◽  
Shail K. Chaube
Keyword(s):  
Oxidative Stress ◽  
Granulosa Cells ◽  
Rat Eggs ◽  
Induced Apoptosis

scholarly journals Activation of endoplasmic reticulum stress mediates oxidative stress–induced apoptosis of granulosa cells in ovaries affected by endometrioma

2019 ◽  
Vol 26 (1) ◽  
pp. 40-52 ◽  
Author(s):  
Chisato Kunitomi ◽  
Miyuki Harada ◽  
Nozomi Takahashi ◽  
Jerilee M K Azhary ◽  
Akari Kusamoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Granulosa Cells ◽  
Ovarian Function ◽  
Stress Sensor ◽  
Local Factor ◽  
High Oxidative Stress ◽  
Induced Apoptosis ◽  
Sensor Proteins

Abstract Endometriosis exerts detrimental effects on ovarian physiology and compromises follicular health. Granulosa cells from patients with endometriosis are characterized by increased apoptosis, as well as high oxidative stress. Endoplasmic reticulum (ER) stress, a local factor closely associated with oxidative stress, has emerged as a critical regulator of ovarian function. We hypothesized that ER stress is activated by high oxidative stress in granulosa cells in ovaries with endometrioma and that this mediates oxidative stress–induced apoptosis. Human granulosa-lutein cells (GLCs) from patients with endometrioma expressed high levels of mRNAs associated with the unfolded protein response (UPR). In addition, the levels of phosphorylated ER stress sensor proteins, inositol-requiring enzyme 1 (IRE1) and double-stranded RNA-activated protein kinase-like ER kinase (PERK), were elevated in granulosa cells from patients with endometrioma. Given that ER stress results in phosphorylation of ER stress sensor proteins and induces UPR factors, these findings indicate that these cells were under ER stress. H2O2, an inducer of oxidative stress, increased expression of UPR-associated mRNAs in cultured human GLCs, and this effect was abrogated by pretreatment with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor in clinical use. Treatment with H2O2 increased apoptosis and the activity of the pro-apoptotic factors caspase-8 and caspase-3, both of which were attenuated by TUDCA. Our findings suggest that activated ER stress induced by high oxidative stress in granulosa cells in ovaries with endometrioma mediates apoptosis of these cells, leading to ovarian dysfunction in patients with endometriosis.

MicroRNA-145 protects follicular granulosa cells against oxidative stress-induced apoptosis by targeting Krüppel-like factor 4

2017 ◽  
Vol 452 ◽  
pp. 138-147 ◽  
Author(s):  
Lu Xu ◽  
Haixiang Sun ◽  
Mei Zhang ◽  
Yue Jiang ◽  
Chunxue Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Granulosa Cells ◽  
Induced Apoptosis

scholarly journals HO-1 reduces heat stress-induced apoptosis in bovine granulosa cells by suppressing oxidative stress

Aging ◽  
2019 ◽  
Vol 11 (15) ◽  
pp. 5535-5547 ◽  
Author(s):  
Yiru Wang ◽  
Caixia Yang ◽  
Nahla Abdalla Hassan Elsheikh ◽  
Chengmin Li ◽  
Fangxiao Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heat Stress ◽  
Granulosa Cells ◽  
Induced Apoptosis

PKCδ contributes to oxidative stress-induced apoptosis in porcine ovarian granulosa cells via activating JNK

2019 ◽  
Vol 131 ◽  
pp. 89-95 ◽  
Author(s):  
Shuo Liu ◽  
Ming Shen ◽  
Chengyu Li ◽  
Yinghui Wei ◽  
Xueqing Meng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Granulosa Cells ◽  
Ovarian Granulosa Cells ◽  
Induced Apoptosis

scholarly journals MON-027 Activation of Endoplasmic Reticulum Stress Mediates Oxidative Stress-Induced Apoptosis of Granulosa Cells in Ovaries Affected by Endometrioma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Chisato Kunitomi ◽  
Miyuki Harada ◽  
Jerilee Mariam Khong Azahry
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Granulosa Cells ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Ovarian Dysfunction ◽  
High Oxidative Stress ◽  
Induced Apoptosis ◽  
Sensor Proteins ◽  
Apoptotic Factors

Abstract Endometriosis exerts detrimental effects on ovarian physiology and compromises follicular health. Granulosa cells of endometriosis patients are characterized by increased apoptosis, as well as high oxidative stress. Among several pathophysiologic factors associated with endometriosis, it is expected that oxidative stress contributes to the induction of apoptosis in granulosa cells, although the underlying mechanism remains unclear. Endoplasmic reticulum (ER) stress, a local factor closely associated with oxidative stress, has emerged as a critical regulator of ovarian function. We hypothesized that ER stress is activated by high oxidative stress in granulosa cells in ovaries with endometrioma and mediates oxidative stress-induced apoptosis. Ovaries from patients with endometrioma and control were collected to determine apoptosis, oxidative stress and ER stress by TUNEL, immunohistochemical staining of 8-OHdG and ER stress sensors, respectively. Human granulosa-lutein cells (GLCs) obtained from IVF patients were cultured with H2O2 (an oxidative stress inducer) or tauroursodeoxycholic acid (TUDCA, an ER stress inhibitor in clinical use) to assess apoptosis and ER stress by quantitative PCR and FACS. Activity of pro-apoptotic factors was determined by caspase-8 activity assay and western blotting for cleaved caspase-3. Human GLCs from patients with endometrioma expressed up to two times higher level of mRNAs associated with the unfolded protein response (UPR), including ATF4, ATF6, the spliced form of XBP1, HSPA5, and CHOP. In addition, the levels of phosphorylated ER stress sensor proteins, IRE1 and PERK, were elevated. Given that ER stress results in phosphorylation of ER stress sensor proteins and induces UPR factors, these findings indicate that these cells were under ER stress. H2O2 increased expression of UPR-associated mRNAs in cultured human GLCs, and this effect was abrogated by pre-treatment with TUDCA. Treatment with H2O2 increased apoptosis and the activity of pro-apoptotic factors caspase-8 and caspase-3, both of which were attenuated by TUDCA. Our findings suggest that activated ER stress induced by high oxidative stress in granulosa cells in ovaries with endometrioma mediates apoptosis of these cells, leading to ovarian dysfunction in endometriosis patients. Targeting ER stress with currently clinically available ER stress inhibitors, or with these agents in combination with antioxidants, may serve as a novel strategy for rescuing endometriosis-associated ovarian dysfunction.

Activation of Nrf2 might reduce oxidative stress in human granulosa cells

2018 ◽  
Vol 470 ◽  
pp. 96-104 ◽  
Author(s):  
Nana Akino ◽  
Osamu Wada-Hiraike ◽  
Hiromi Terao ◽  
Harunori Honjoh ◽  
Wataru Isono ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Granulosa Cells ◽  
Human Granulosa Cells

Autophagy Contributes to Oxidative Stress-Induced Apoptosis in Porcine Granulosa Cells

2020 ◽  
Author(s):  
Jia-Qing Zhang ◽  
Qiao-Ling Ren ◽  
Jun-Feng Chen ◽  
Bin-Wen Gao ◽  
Xian-Wei Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Granulosa Cells ◽  
Porcine Granulosa Cells ◽  
Induced Apoptosis
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