Table 3 The role of Nrf2 in granulosa cells

Aglan HS et al. [84]

Bovine GCs

In-vitro

Lead

• Lead downregulate Nrf2, NF-κB, and antiapoptotic gene

• Lead upregulates the expression of endoplasmic reticulum stress marker and the proapoptotic gene

• Lead induces GCs cycle arrest and mediates apoptosis via disruption of Nrf2/NF-κB

• Lead to decrease in the expression of cell proliferation marker genes in GCs

Sammad A et al. [72]

Bovine GCs

In-vitro

Acute Heat Stress

• Acute Heat Stress upregulate inflammatory, pro-apoptotic, caspase executioner genes, antioxidants and anti-apoptotic genes

• High inflammatory responsible oxidative-stress-mediated apoptosis in GCs via NF-κB pathway and repression of the Nrf2 pathway

• Acute Heat Stress induces transient cellular senescence and apoptosis in GCs via MAPK and p53 signaling pathway

Esfandyari S et al. [80]

Human GCs

In-vitro

Pretreatment of GCs with Sulforaphane

• SFN attenuated intracellular ROS production and apoptosis rate in the GCs

• SFN increases the mRNA expression level of Nrf2, SOD, and CAT

Eslami M et al. [73]

Human GCs

In-vitro

Astaxanthin

• AST suppresses ROS generation and cell death in GCs

• AST elevates gene and protein expression of Nrf2 and inhibits the protein of KEAP

Li M et al. [83]

Goat GCs

In-vitro

Quercetin

• Que decreased GCs apoptosis by downregulate expressions of BAX, BCL-2, Caspase 3, and Cleaved caspase 3

• Que increases cellular viability by upregulating Nrf2 and its downstream genes

Ma Y et al. [81]

Human GCs

In-vitro

Pretreatment with morroniside

• Morningside decreases the levels of ROS, MDA, and 8-OHdG in GCs

• Morroniside upregulates p-Nrf2 and promoted the nuclear translocation of Nrf2, which transcriptionally activated antioxidant SOD and NQO1

• Morroniside regulates the levels of apoptosis-related proteins via the p38 and JNK pathways

Rashidi Z et al. [82]

Human GCs

In-vitro

Quercetin

• Que pretreatment decreases ROS production and apoptosis

• Que increases the Nrf2 gene and protein expression and its nuclear translocation and decreases the level of Keap1 protein

• Que protected GCs from OS by increasing Thrx gene expression and activity

Sohel MMH et al. [79]

Bovine GCs

In-vitro

Pretreatment of Sulforaphane

• SFN increases cell viability and reduces cytotoxicity in GCs

• SFN increases the expression of Nrf2 and the relative abundance of the Nrf2 downstream target antioxidant genes

Sohel MMH et al. [30]

Bovine GCs

In-vitro

Pretreatment of Sulforaphane

• Higher concentrations of SFN have cytotoxic effects on GCs

• SFN regulates Nrf2, genes downstream to Nrf2, and Keap1expression

• SFN has concentration-dependent antioxidative and apoptotic effects on GCs

Wang M et al. [75]

Bovine GCs

In-vitro

Pretreated with Vitamin E

• VE decreases the intracellular ROS levels, increases the MDA content, and improves the antioxidant enzyme activity in a dose-dependent manner

• VE promotes proliferation and inhibits apoptosis in GCs via the Nrf2 pathway

Wang M et al. [33]

Bovine GCs

In-vitro

vitamin E (VE) and selenium (Se)

• VE or Se could stimulate the GCs proliferation

• VE or Se increased the secretion of estradiol and progesterone

• VE or Se down-regulates the apoptosis-related gene expression, inhibits ROS and MDA generation, and increases T-AOC, and the activities of SOD, CAT, and GSH-Px

• VE or Se alleviates the endoplasmic reticulum stress, activates the NRF2, and up-regulated the expression of its downstream genes

Zou L et al. [85]

Human GCs

In-vitro

Copper model and

pretreated with Hemin

• Copper decreases GCs viability and the mitochondrial membrane potential, increases the apoptosis rate, and induces OS

• Hemin pretreatment induces HO-1 expression in GCs via the MAPK14-Nrf2 pathway, reduces the accumulation of ROS, and increases the levels of antioxidant enzymes