Abstract
Cryopreservation and transplantation of ovarian tissue is the only fertility preservation option used for prepubertal girls and women who don’t have a chance for embryo or oocyte vitrification. For women with aggressive cancer, hormone-responsive malignancies, autoimmune diseases, etc. ovary transplantation cannot be performed so an alternative technology called in-vitro follicle activation is thinkable. In this method, dormant primordial follicles are activated from the resting primordial pool by in-vitro culture and enter their growth phase. Different in-vitro culture media and supplements in addition to various culturing methods have been conducted for activating these dormant follicles. Furthermore, several signaling pathways such as Hippo, phosphatidylinositol-3-kinase, and mTOR influence follicle activation. Therefore, the addition of different activators of these signaling pathways can beneficially regulate this culture system. This review summarizes the findings on different aspects of human ovarian tissue culture strategies for in-vitro follicular activation, their medium, and different factors involved in this activation. Afterward, signaling pathways important for follicle activation and their clinical applications towards improving activation in culture are also reviewed.
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Abbreviations
- α-MEM:
-
Alpha minimal essential medium
- Akt1:
-
Protein kinase B
- AMH:
-
Anti-Müllerian hormone
- bFGF:
-
Basic fibroblast growth factor
- BMP:
-
Bone morphogenetic protein
- CCN:
-
Connective tissue growth factor (CTGF), Cystein rich protein (Cyr61), and Nephroblastoma overexpressed genes
- DOR:
-
Diminished ovarian reserve
- E2:
-
Estradiol
- EBSS:
-
Earle’s balanced salt solution
- ECM:
-
Extracellular matrix
- FGF:
-
Fibroblast growth factor
- FSH:
-
Follicle stimulating hormone
- GDF9:
-
Growth differentiation factor 9
- HSA:
-
Human serum albumin
- hUC-MSC:
-
Human umbilical cord mesenchymal stem cells
- ITS:
-
Insulin-transferin-selenium
- IVA:
-
In-vitro activation
- IVF:
-
In-vitro fertilization
- LATSI1/2:
-
Large tumor suppressor kinases 1 and 2
- mTOR:
-
Mammalian target of rapamycin
- MST1/2:
-
Mammalian Ste-20 like kinases 1 and 2
- PDK1:
-
3-Phosphoinositide dependent kinase-1
- PEG:
-
Polyethylene glycol
- PI3K:
-
Phosphatidylinositol 3 kinase
- POI:
-
Premature ovarian insufficiency
- PTEN:
-
Protein phosphatase with TENsin homolog
- rpS6:
-
Ribosomal protein S6
- S1p:
-
Sphingosine-1-phosphate
- Smad:
-
Caenorhabditis elegans SMA (“small” worm phenotype) and Drosophila MAD (“Mothers Against Decapentaplegic”)
- TAZ:
-
Transcriptional coactivator PDZ-binding motif
- Tsc:
-
Tumor suppressor tuberous sclerosis complex
- YAP:
-
Yes associated protein
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ZG: Performed the literature search and manuscript writing; NK-R: Manuscript writing and image illustration; BE: Idea for the article and manuscript revision.
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Ghezelayagh, Z., Khoshdel-Rad, N. & Ebrahimi, B. Human ovarian tissue in-vitro culture: primordial follicle activation as a new strategy for female fertility preservation. Cytotechnology 74, 1–15 (2022). https://doi.org/10.1007/s10616-021-00510-2
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DOI: https://doi.org/10.1007/s10616-021-00510-2