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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

FOXO1↑ → WNT4↑,PRL↑,IGFBP1↑

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