1. In-vitro regulation of primordial follicle activation: challenges for fertility preservation strategies 
Michael J. Bertoldo, Kirsty A. Walters, William L. Ledger, Robert B. Gilchrist, Pascal Mermillod, Yann Locatelli 
Reproductive BioMedicine Online 
Volume 36, Issue 5, Pages (May 2018)
DOI: /j.rbmo
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2. Figure 1
Fertility preservation strategies for females before cancer treatment. Treatments are tailored to patients depending on the patient's age, the possible delay in treatment and sensitivity of malignancy to hormone treatment. Experimental procedures are enclosed in green boxes. IVM = in vitro maturation.
Reproductive BioMedicine Online  , DOI: ( /j.rbmo )
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3. Figure 2
Culture of cortical tissue permits the activation of primordial follicles. Once follicle growth is initiated, follicles have the potential to develop into multilaminar structures up to the secondary follicle size. However, at this point of development, the cortical environment that nurtured the first stages of follicle development becomes inhibitory for growth to pass the secondary follicle stage. The pre-antral follicles can be mechanically isolated from the cortex, encapsulated in an alginate hydrogel and placed into individual culture for further differentiation to the antral stage. Following formation of the antrum, follicles can then be removed from the hydrogel and cultured in low attachment plates. Oocytes within can be mechanically extracted from the follicle and placed into IVM and subsequently undergo IVF.
Adapted from Telfer and McLaughlin (2011) and Xiao et al. (2015).
Reproductive BioMedicine Online  , DOI: ( /j.rbmo )
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4. Figure 3
Molecular pathways regulating primordial follicle activation. The PI3K/Akt/mTOR pathway has many substrates which include molecules regulating cell cycle and apoptosis. Akt can phosphorylate Foxo3a and cause cytoplasmic localization of this transcription factor. When unphosphorylated, Foxo3a and p27 relocate to the nucleus and inhibit primordial follicle activation. Inhibition of Foxo3a translocation may also be regulated by the JNK/c-Jun pathway. Phosphorylation and inactivation of TSC by Akt leads to the activation of mTORC1. mTORC1 integrates cellular energy levels, growth factors and other signals that regulate protein translation and primordial follicle activation. 4E-BP1 = 4E binding protein; Akt = protein kinase B; EIF4B = eukaryotic translation initiation factor 4B; mTOR = mammalian target of rapamycin complex; p27 = p27kip1; PDK1 = 3′-phosphoinositide-dependent kinase-1; PI3K = phosphatidylinositol-3-kinase; PIP2 = phosphatidylinositol-4,5-biphosphate; PIP3 = phosphatidylinositol-3,4,5-triphosphate; PTEN = phosphatase and tensin homologue deleted on chromosome 10; rpS6 = ribosomal protein S6; S6K = S6 kinase; TSC = tuberin/tuberous sclerosis complex.
Adapted from Adhikari and Liu (2009).
Reproductive BioMedicine Online  , DOI: ( /j.rbmo )
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