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Table 2 The important proteins in reproductive mechanisms

From: A novel and compact review on the role of oxidative stress in female reproduction

Protein Function and role in reproductive process Interaction between proteins Reference
Keap1-Nrf2 pathway Keap1: Keap1 binds to Nrf2 in cytoplasm.
Nrf2: Protects cells under moderate oxidative stress
A regulator of antioxidant defense in vascular dysfunction and oxidative damage.
Deletion of Nrf2 → Fetal DNA damage and nervous system defects (the basis of trophoblast cell apoptosis).
Vaginal delivery and Uterine infection: Nrf2↓
The right amount of OS → Nrf2↑ → HO-1↑,NQO1↑,GCLC↑
Excessive OS → FOXO3↑ → Ability of Keap1 to bind to Nrf2↑
Deletion of FOXO3: OS↑ → AKT↑ → Nrf2↑
[91,92,93, 95,96,97,98]
NF-κB pathway An active molecule in the immune system;
Redox-Sensitive transcription factors
Placental stress: OS → NF-κB↑ → Pro-inflammatory Cytokines↑ → Placental apoptotic process is activated
Endometriosis: OS↑ → TNF-α↑ → NF-κB↑
In vitro: IL-1β → NF-κB↑ → MIF↑, TNF-α↑
Inhibitory IκB protein family binds to NF-κB in cytoplasm
IKKB protein is degraded (IKKα, IKKβ, NEMO mediate) → NF-κB enters nuclear to regulate target gene.
IKKβ↑ → p-FOXO3↑
Deletion of FOXO3 → NF-κB↓
FOXO3↑ → BCL10↑ → IKKB↓ → NF-κB↑ → Anti-apoptosis gene↑
[2, 99,100,101,102,103,104, 108, 109]
FOXO family FOXO1(all tissues): Deletion of FOXO1, embryonic cell death due to incomplete blood vessel development
FOXO3(all tissues): Deletion of FOXO1, lymphocyte proliferation, extensive organ inflammation
FOXO4 (muscle, kidney, colorectal): Deletion of FOXO4, inflammation of the colon in response to inflammatory stimuli
FOXO6(brain, liver): Deletion of FOXO6, shows normal learning, but memory consolidation is impaired
FOXO1↑ → Apoptotic pathway in decidual stromal cells, and Inhibits endometrial epithelial cell growth
JNK↑ → FOXO1↑ → MnSOD↑, CAT↑ → Protecting cells
[111, 112, 115,116,117,118,119,120]
MAPK family JNK: Activated by stress and inflammation
P38 MAPK: Activated by stress and inflammation
ERK: Activated by inflammation and growth factors
OS↑ → p38 MAPK↑ → Aging and premature aging of fetal tissue
Endometriosis: ERK↑
Endometrial stromal cells: time of p-ERK↑; OS↑ → ERK↑,H2O2↑ → p-ERK↑
JNK↑ → FOXO1↑ → MnSOD↑, CAT↑ → Protecting cells
P450↑ → ROS↑ → ASK1-P-p38 MAPK
[118, 121, 123,124,125,126, 129, 130]
  1. The ‘→’ indicates that it has an effect on the next step. The ‘↑’ represents an increase and the ‘↓‘represents a decrease