Table 6.
The immunological and gene therapy in the POF animal model
| Immune agents/genes | POF model | Immunological/gene therapy | Immunological/gene therapy from references | ||||
|---|---|---|---|---|---|---|---|
| Animal | Drug | Method | Treatment | Assessment | Mechanism | ||
| TP-5 | C57BL/6 mice (10 weeks) |
HFHS (High-fat diet 8 g/kg + 200 μL of 30% high fructose syrup once a day via gavage) for 2 m |
TP-5 (5 mg/kg) for 2 m |
Ip |
Decrease atretic follicles Increase ovary weight Increase peripheral blood E2 levels Improve lipid oxidative stress injury and blood lipids Attenuate proportion and activation of CD3+ T cells and type I macrophages |
TP-5 upregulates BMP4/Smad9 signaling pathway to promote the balance and polarization of immune cell, and reduces the release of inflammatory factors and lipid oxidative stress injury | [37] |
| TrkB agonist antibody (Ab4B19) |
C57BL/6 mice (6–8 w) |
CTX (a single, 75 mg/kg, 200–300 μL) for 7 days |
Ab4B19 (1 mg/kg), once every 4 days, for 16 days |
iv |
Promote oocyte maturation and follicle development Attenuate ovarian degradation Normalize gonadal hormone Inhibit apoptosis Enhance fertility |
NO Report | [30] |
| pcD-mZP3 + mZP3 protein vaccine |
C57BL/6 mice (8–10 weeks) |
mZP3 (0.1 ml of 100 µg of CFA emulsified mZP3) | 100 µg DNA and 100 µg protein vaccines per mouse | - |
Ameliorate autoimmune ovarian disease Promote anti-inflammatory function Down-regulate the antigen-specific T-cell responses Induce adaptive Tr cells |
The induction of the CD4+CD25−Foxp3+IL-10+ Treg cells suppress mZP3 antigen-specific T cell responses in vitro with decreasing the anti-inflammatory cytokine production | [98] |
| Prednisone | POF patients | – | 25 mg four times per day for 2 weeks | – | 2/11 patients demonstrated biochemical normalization, evidence of follicular growth by a rise of E2, and visualization on ultrasonography, and both spontaneously ovulated, conceived, had uneventful pregnancies, and delivered healthy children | NO Report | [99] |
| NEAT1/miR-654 |
C57BL/6 mice (8 weeks) |
CTX (30 mg/kg every other day for 3 weeks) | – | Cell transfection | Eliminates the promoting effect of CTX on OGC apoptosis and autophagy | NEAT1 overexpression inhibits miR-654 and further regulates STC2/MAPK pathway | [103] |
| miR-146a | OGCs | – | 80 nM miR‑146a inhibitor/wk | Cell transfection | Inhibit granulosa cell apoptosis | Attenuates the activation of miR‑146a/IRAK1/TRAF6/caspase‑8 signaling | [104] |
| miRNA-190a-5p |
SD rats (12 weeks, 200 ± 20 g) |
VCD (80 mg/kg/d for 15 days ) | No treatment | Promotes primordial follicle hyperactivation | miRNA-190a-5p inhibits the expression of PHLPP1 and key proteins in the AKT-FOXO3a and AKT-LH/LHR pathways | [105] | |
| miR-146b-5p | C57BL/6 mice (10 weeks) | HFHS diet (8 g/kg bodyweight + 400 μL of 30% d-glucose for 30 days ) | 400 μL of miR-146@ PLGA (20 mg/mL) once every 3 days | iv |
Mitigates the HFHS-induced oxidative stress injury and aging in OGCs Increase ovary weight Increase the number of normal follicles, decrease the number of atretic follicle Increase the peripheral blood levels of estradiol, progesterone and 17α-hydroxy pregnenolone Decrease the peripheral blood levels of testosterone and dihydrotestosterone |
miR-146b-5p overexpression attenuates the activation of the Dab2ip/Ask1/p38-Mapk signaling pathway and γH2A.X phosphorylation | [100] |
| miR-133b | ICR mice (21 days ) | – | – | Cell transfection | Stimulates estrogen synthesis in OGCs | miR-133b down-regulates Foxl2 expression in OGCs by directly targeting the 30UTR, and inhibits the Foxl2-mediated transcriptional repression of StAR and CYP19A1 | [101] |
| TRERNA1 | KGN cells | – | 10 mM TRERNA1 vector/107 cells | Cell transfection | Inhibit KGN cells apoptosis | TRERNA1 may sponge miR-23a to suppress OGCs apoptosis in POF | [102] |
TP-5 thymopentin, HFHS high-fat diet, TGs tripterygium glycosides, OGCs ovarian granular cells, VCD 4-vinylcyclohexene dicyclic oxide, HFHS high-fat diet, VCD 4-vinylcyclohexene diepoxide