Table 2.

The important proteins in reproductive mechanisms

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↑	[91–93, 95–98]
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, 99–104, 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, 115–120]
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, 123–126, 129, 130]

The ‘→’ indicates that it has an effect on the next step. The ‘↑’ represents an increase and the ‘↓‘represents a decrease