Platelet-activating factor-stimulated production of reactive oxygen species in ovarian granulosa cells from periovulatory follicles

2009 ◽  
Vol 75A (8) ◽  
pp. 658-664 ◽  
Author(s):  
Jinxian Xu ◽  
Burkhard Krüger ◽  
Andreas Vernunft ◽  
Berthold Löhrke ◽  
Torsten Viergutz
Keyword(s):  
Reactive Oxygen Species ◽  
Granulosa Cells ◽  
Platelet Activating Factor ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Ovarian Granulosa Cells ◽  
Periovulatory Follicles

scholarly journals Non-esterified Fatty Acid-Induced Reactive Oxygen Species Mediated Granulosa Cells Apoptosis Is Regulated by Nrf2/p53 Signaling Pathway

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 523
Author(s):  
Yiru Wang ◽  
Chengmin Li ◽  
Julang Li ◽  
Genlin Wang ◽  
Lian Li
Keyword(s):  
Reactive Oxygen Species ◽  
Fatty Acid ◽  
Granulosa Cells ◽  
Ovarian Function ◽  
Reactive Oxygen ◽  
Follicular Development ◽  
Oxygen Species ◽  
Related Protein ◽  
Induced Apoptosis

Negative energy balance (NEB) during the perinatal period can affect dairy cow follicular development and reduce the fecundity. Non-esterified fatty acid (NEFA) concentration is elevated during NEB, and is known to be toxic for multiple cell types. In the ovary, NEB increased NEFA, and may influences follicular growth and development. However, the effect and mechanism of NEFA on granulosa cells (GCs) in vitro remains unknown. In this study, we found that NEFA dose-dependently induced apoptosis in primary cultured granulosa cells. Mechanistically, our data showed that NEFA significantly increased reactive oxygen species (ROS) levels, resulting in the activation of endoplasmic reticulum stress (ERS) and eventually cell apoptosis in GCs. Moreover, NEFA also increased the phosphorylation levels of ERK1/2 and p38MAPK pathways, upregulated the expression of p53 and potentially promoted its translocation to the nuclear, thus transcriptionally activated Bax, a downstream gene of this pathway. NEFA also promoted nuclear factor E2 (Nrf2) expression and its level in the nuclear. To elucidate the mechanism of NEFA action, N-acetyl-l-cysteine (NAC), a ROS scavenger was used to verify the role of ROS in NEFA induced apoptosis of GCs. NAC pretreatment reversed the NEFA-induced ERS-related protein and apoptosis-related protein levels. Meanwhile, NAC pretreatment also blocked the phosphorylation of ERK1/2 and p38 induced by NEFA, and the nucleation of Nrf2 and p53, suggesting that ROS plays a crucial role in regulating the NEFA-induced apoptosis of GCs. Together, these findings provide an improved understanding of the mechanisms underlying GCs apoptosis, which could potentially be useful for improving ovarian function.

scholarly journals HIF1A-dependent increase in endothelin 2 levels in granulosa cells: role of hypoxia, LH/cAMP, and reactive oxygen species

Reproduction ◽  
2015 ◽  
Vol 149 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Ronit Yalu ◽  
Adepeju Esther Oyesiji ◽  
Iris Eisenberg ◽  
Tal Imbar ◽  
Rina Meidan
Keyword(s):  
Reactive Oxygen Species ◽  
Mrna Expression ◽  
Granulosa Cells ◽  
Time Window ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Protein Levels ◽  
Concomitant Reduction

Hypoxia-inducible factor 1 alpha (HIF1A) and endothelin 2 (EDN2) are transiently expressed during the same time window in the developing corpus luteum (CL). In this study, we sought to investigate the involvement of LH/cAMP, reactive oxygen species (ROS), and a hypoxia-mimetic compound (CoCl2) on HIF1A expression and how it affected EDN2 levels, using transformed human granulosa cells (thGCs) and primary bovine granulosa cells (GCs). CoCl2 elevated HIF1A protein levels in thGCs in a dose-dependent manner. Forskolin alone had no significant effect; however, forskolin and CoCl2 together further induced HIF1A protein and EDN2 mRNA expression in thGCs. Similarly, in primary GCs, LH with CoCl2 synergistically augmented HIF1A protein levels, which resulted in higher expression of EDN2 and another well-known hypoxia-inducible gene, VEGF (VEGFA). Importantly, LH alone elevated HIF1A mRNA but not its protein. The successful knockdown of HIF1A in thGCs using siRNA abolished hypoxia-induced EDN2 and also the additive effect of forskolin and CoCl2. We then examined the roles of ROS in thGCs: hydrogen peroxide (20 and 50 μM) elevated HIF1A protein as well as the expression of EDN2, implying that induction of HIF1A protein levels is sufficient to stimulate the expression of EDN2 (and VEGF) in normoxia. A broad-range ROS scavenger, butylated hydroxyanisole, inhibited CoCl2-induced HIF1A protein with a concomitant reduction in the mRNA expression of EDN2 and VEGF in thGCs. The results obtained in this study suggest that HIF1A, induced by various stimuli, is an essential mediator of EDN2 mRNA expression. The results may also explain the rise in the levels of HIF1A-dependent genes (EDN2 and VEGF) in the developing CL.

scholarly journals Mutation of rat Zp2 causes ROS-mediated oocyte apoptosis

Reproduction ◽  
2020 ◽  
Vol 160 (3) ◽  
pp. 353-365
Author(s):  
Yan Wang ◽  
Hualin Huang ◽  
Minghua Zeng ◽  
Ru-Ping Quan ◽  
Jun-Ting Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Granulosa Cells ◽  
Rat Model ◽  
Zona Pellucida ◽  
Reactive Oxygen ◽  
Fertilization Rate ◽  
Oocyte Development ◽  
Oxygen Species ◽  
Bidirectional Signaling

In this study, we investigated a gene-edited (Zp2MT/MT) rat model of infertility caused by the failure to express the zona pellucida glycoprotein 2 (ZP2) due to the significant reduction of mRNA amount. We examined the defects in the zona pellucida (ZP) caused by ZP2 nullification and the influence of these defects on aspects of oocyte development, including apoptosis and fertilization ability. To investigate the cause of the influence to the oocytes’ development, we evaluated the morphology of follicular transzonal projections (TZPs), known as ‘bridges’, which mediate the bidirectional signaling between the oocyte and surrounding granulosa cells and the level of reactive oxygen species (ROS) in ovulated eggs. Our results showed that two types of ZP defects were generated in the Zp2MT/MT rat,that is, ZP intact but thinned and ZP cracked (or even absent). The fertilization rate of the ovulated eggs reduced in both types, while increased oocyte apoptosis was observed only in the latter type. Moreover, the increased oocyte apoptosis rate correlated closely with the reduction in follicular TZPs and increased ROS levels in ovulated egg. In conclusion, nullification of rat ZP2 destroyed the integrity of the ZP, impaired the bidirectional signaling between the oocyte and surrounding granulosa cells. Therefore, the resulting infertility likely occurs via elevation of oxidative stress and oocytes apoptosis.

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