Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
권호 표지
DOI QR코드

DOI QR Code

Primordial follicle activation as new treatment for primary ovarian insufficiency

  • Lee, Hye Nam (Department of Obstetrics and Gynecology, Fertility Center, CHA Gangnam Medical Center, CHA University) ;
  • Chang, Eun Mi (Department of Obstetrics and Gynecology, Fertility Center, CHA Gangnam Medical Center, CHA University)
  • Received : 2019.04.01
  • Accepted : 2019.05.16
  • Published : 2019.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Primordial follicle activation is a process in which individual primordial follicles leave their dormant state and enter a growth phase. While existing hormone stimulation strategies targeted the growing follicles, the remaining dormant primordial follicles were ruled out from clinical use. Recently, in vitro activation (IVA), which is a method for controlling primordial follicle activation, has provided an innovative technology for primary ovarian insufficiency (POI) patients. IVA was developed based on Hippo signaling and phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/forkhead box O3 (FOXO3) signaling modulation. With this method, dormant primordial follicles are activated to enter growth phase and developed into competent oocytes. IVA has been successfully applied in POI patients who only have a few remaining remnant primordial follicles in the ovary, and healthy pregnancies and deliveries have been reported. IVA may also provide a promising option for fertility preservation in cancer patients and prepubertal girls whose fertility preservation choices are limited to tissue cryopreservation. Here, we review the basic mechanisms, translational studies, and current clinical results for IVA. Limitations and further study requirements that could potentially optimize IVA for future use will also be discussed.

Keywords

References

  1. De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet 2010;376:911-21. https://doi.org/10.1016/S0140-6736(10)60355-8
  2. Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol 1986;67:604-6.
  3. Nelson LM. Clinical practice: primary ovarian insufficiency. N Engl J Med 2009;360:606-14. https://doi.org/10.1056/NEJMcp0808697
  4. European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI, Webber L, Davies M, Anderson R, Bartlett J, Braat D, et al. ESHRE guideline: management of women with premature ovarian insufficiency. Hum Reprod 2016;31:926-37. https://doi.org/10.1093/humrep/dew027
  5. Cordts EB, Christofolini DM, Dos Santos AA, Bianco B, Barbosa CP. Genetic aspects of premature ovarian failure: a literature review. Arch Gynecol Obstet 2011;283:635-43. https://doi.org/10.1007/s00404-010-1815-4
  6. Haller-Kikkatalo K, Uibo R, Kurg A, Salumets A. The prevalence and phenotypic characteristics of spontaneous premature ovarian failure: a general population registry-based study. Hum Reprod 2015;30:1229-38. https://doi.org/10.1093/humrep/dev021
  7. Woad KJ, Watkins WJ, Prendergast D, Shelling AN. The genetic basis of premature ovarian failure. Aust N Z J Obstet Gynaecol 2006;46:242-4. https://doi.org/10.1111/j.1479-828X.2006.00585.x
  8. McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocr Rev 2000;21:200-14. https://doi.org/10.1210/edrv.21.2.0394
  9. Skinner MK. Regulation of primordial follicle assembly and development. Hum Reprod Update 2005;11:461-71. https://doi.org/10.1093/humupd/dmi020
  10. Adhikari D, Flohr G, Gorre N, Shen Y, Yang H, Lundin E, et al. Disruption of Tsc2 in oocytes leads to overactivation of the entire pool of primordial follicles. Mol Hum Reprod 2009;15:765-70. https://doi.org/10.1093/molehr/gap092
  11. Ding X, Zhang X, Mu Y, Li Y, Hao J. Effects of BMP4/SMAD signaling pathway on mouse primordial follicle growth and survival via up-regulation of Sohlh2 and c-kit. Mol Reprod Dev 2013;80:70-8. https://doi.org/10.1002/mrd.22138
  12. Lee WS, Otsuka F, Moore RK, Shimasaki S. Effect of bone morphogenetic protein-7 on folliculogenesis and ovulation in the rat. Biol Reprod 2001;65:994-9. https://doi.org/10.1095/biolreprod65.4.994
  13. Tang K, Yang WC, Li X, Wu CJ, Sang L, Yang LG. GDF-9 and bFGF enhance the effect of FSH on the survival, activation, and growth of cattle primordial follicles. Anim Reprod Sci 2012;131:129-34. https://doi.org/10.1016/j.anireprosci.2012.03.009
  14. Huang EJ, Manova K, Packer AI, Sanchez S, Bachvarova RF, Besmer P. The murine steel panda mutation affects kit ligand expression and growth of early ovarian follicles. Dev Biol 1993;157:100-9. https://doi.org/10.1006/dbio.1993.1115
  15. Yoshida H, Takakura N, Kataoka H, Kunisada T, Okamura H, Nishikawa SI. Stepwise requirement of c-kit tyrosine kinase in mouse ovarian follicle development. Dev Biol 1997;184:122-37. https://doi.org/10.1006/dbio.1997.8503
  16. Kezele PR, Nilsson EE, Skinner MK. Insulin but not insulin-like growth factor-1 promotes the primordial to primary follicle transition. Mol Cell Endocrinol 2002;192:37-43. https://doi.org/10.1016/S0303-7207(02)00114-4
  17. Nilsson EE, Larsen G, Skinner MK. Roles of Gremlin 1 and Gremlin 2 in regulating ovarian primordial to primary follicle transition. Reproduction 2014;147:865-74. https://doi.org/10.1530/REP-14-0005
  18. Nilsson EE, Kezele P, Skinner MK. Leukemia inhibitory factor (LIF) promotes the primordial to primary follicle transition in rat ovaries. Mol Cell Endocrinol 2002;188:65-73. https://doi.org/10.1016/S0303-7207(01)00746-8
  19. Durlinger AL, Kramer P, Karels B, de Jong FH, Uilenbroek JT, Grootegoed JA, et al. Control of primordial follicle recruitment by anti-Mullerian hormone in the mouse ovary. Endocrinology 1999;140:5789-96. https://doi.org/10.1210/endo.140.12.7204
  20. Bonnet A, Cabau C, Bouchez O, Sarry J, Marsaud N, Foissac S, et al. An overview of gene expression dynamics during early ovarian folliculogenesis: specificity of follicular compartments and bidirectional dialog. BMC Genomics 2013;14:904. https://doi.org/10.1186/1471-2164-14-904
  21. Hosaka T, Biggs WH 3rd, Tieu D, Boyer AD, Varki NM, Cavenee WK, et al. Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proc Natl Acad Sci U S A 2004;101:2975-80. https://doi.org/10.1073/pnas.0400093101
  22. Castrillon DH, Miao L, Kollipara R, Horner JW, DePinho RA. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science 2003;301:215-8. https://doi.org/10.1126/science.1086336
  23. Reddy P, Liu L, Adhikari D, Jagarlamudi K, Rajareddy S, Shen Y, et al. Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. Science 2008;319:611-3. https://doi.org/10.1126/science.1152257
  24. John GB, Gallardo TD, Shirley LJ, Castrillon DH. Foxo3 is a PI3Kdependent molecular switch controlling the initiation of oocyte growth. Dev Biol 2008;321:197-204. https://doi.org/10.1016/j.ydbio.2008.06.017
  25. Chang EM, Lim E, Yoon S, Jeong K, Bae S, Lee DR, et al. Cisplatin induces overactivation of the dormant primordial follicle through PTEN/AKT/FOXO3a pathway which leads to loss of ovarian reserve in mice. PLoS One 2015;10:e0144245. https://doi.org/10.1371/journal.pone.0144245
  26. Xu M, Sun J, Wang Q, Zhang Q, Wei C, Lai D. Chronic restraint stress induces excessive activation of primordial follicles in mice ovaries. PLoS One 2018;13:e0194894. https://doi.org/10.1371/journal.pone.0194894
  27. Hu Y, Yuan DZ, Wu Y, Yu LL, Xu LZ, Yue LM, et al. Bisphenol A initiates excessive premature activation of primordial follicles in mouse ovaries via the PTEN signaling pathway. Reprod Sci 2018;25:609-20. https://doi.org/10.1177/1933719117734700
  28. Matsuda S, Nakanishi A, Wada Y, Kitagishi Y. Roles of PI3K/AKT/PTEN pathway as a target for pharmaceutical therapy. Open Med Chem J 2013;7:23-9. https://doi.org/10.2174/1874104501307010023
  29. Imai Y, Yamagishi H, Ono Y, Ueda Y. Versatile inhibitory effects of the flavonoid-derived PI3K/Akt inhibitor, LY294002, on ATPbinding cassette transporters that characterize stem cells. Clin Transl Med 2012;1:24. https://doi.org/10.1186/2001-1326-1-24
  30. Gross ER, Peart JN, Hsu AK, Auchampach JA, Gross GJ. Extending the cardioprotective window using a novel delta-opioid agonist fentanyl isothiocyanate via the PI3-kinase pathway. Am J Physiol Heart Circ Physiol 2005;288:H2744-9. https://doi.org/10.1152/ajpheart.00918.2004
  31. Gills JJ, Dennis PA. Perifosine: update on a novel Akt inhibitor. Curr Oncol Rep 2009;11:102-10. https://doi.org/10.1007/s11912-009-0016-4
  32. Guo Y, Kwiatkowski DJ. Equivalent benefit of rapamycin and a potent mTOR ATP-competitive inhibitor, MLN0128 (INK128), in a mouse model of tuberous sclerosis. Mol Cancer Res 2013;11:467-73. https://doi.org/10.1158/1541-7786.MCR-12-0605
  33. Albiges L, Chamming's F, Duclos B, Stern M, Motzer RJ, Ravaud A, et al. Incidence and management of mTOR inhibitor-associated pneumonitis in patients with metastatic renal cell carcinoma. Ann Oncol 2012;23:1943-53. https://doi.org/10.1093/annonc/mds115
  34. Pan D. The hippo signaling pathway in development and cancer. Dev Cell 2010;19:491-505. https://doi.org/10.1016/j.devcel.2010.09.011
  35. Cheng Y, Feng Y, Jansson L, Sato Y, Deguchi M, Kawamura K, et al. Actin polymerization-enhancing drugs promote ovarian follicle growth mediated by the Hippo signaling effector YAP. FASEB J 2015;29:2423-30. https://doi.org/10.1096/fj.14-267856
  36. Adhikari D, Gorre N, Risal S, Zhao Z, Zhang H, Shen Y, et al. The safe use of a PTEN inhibitor for the activation of dormant mouse primordial follicles and generation of fertilizable eggs. PLoS One 2012;7:e39034. https://doi.org/10.1371/journal.pone.0039034
  37. Li J, Kawamura K, Cheng Y, Liu S, Klein C, Liu S, et al. Activation of dormant ovarian follicles to generate mature eggs. Proc Natl Acad Sci U S A 2010;107:10280-4. https://doi.org/10.1073/pnas.1001198107
  38. Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, et al. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A 2013;110:17474-9. https://doi.org/10.1073/pnas.1312830110
  39. Suzuki N, Yoshioka N, Takae S, Sugishita Y, Tamura M, Hashimoto S, et al. Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod 2015;30:608-15. https://doi.org/10.1093/humrep/deu353
  40. Zhai J, Yao G, Dong F, Bu Z, Cheng Y, Sato Y, et al. In vitro activation of follicles and fresh tissue auto-transplantation in primary ovarian insufficiency patients. J Clin Endocrinol Metab 2016;101:4405-12. https://doi.org/10.1210/jc.2016-1589
  41. Fabregues F, Ferreri J, Calafell JM, Moreno V, Borras A, Manau D, et al. Pregnancy after drug-free in vitro activation of follicles and fresh tissue autotransplantation in primary ovarian insufficiency patient: a case report and literature review. J Ovarian Res 2018;11:76. https://doi.org/10.1186/s13048-018-0447-3
  42. Check JH, Wilson C, DiAntonio G, DiAntonio A. In vitro fertilization (IVF) outcome in women in overt menopause attempting to induce follicular maturation by follicle stimulating hormone (FSH) receptor down-regulation. Clin Exp Obstet Gynecol 2016;43:181-3. https://doi.org/10.1016/j.ogc.2016.01.004
  43. McLaughlin M, Kinnell HL, Anderson RA, Telfer EE. Inhibition of phosphatase and tensin homologue (PTEN) in human ovary in vitro results in increased activation of primordial follicles but compromises development of growing follicles. Mol Hum Reprod 2014;20:736-44. https://doi.org/10.1093/molehr/gau037
  44. McLaughlin M, Albertini DF, Wallace WH, Anderson RA, Telfer EE. Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system. Mol Hum Reprod 2018;24:135-42. https://doi.org/10.1093/molehr/gay002
  45. Resetkova N, Hayashi M, Kolp LA, Christianson MS. Fertility preservation for prepubertal girls: update and current challenges. Curr Obstet Gynecol Rep 2013;2:218-25. https://doi.org/10.1007/s13669-013-0060-9
  46. Kallen A, Polotsky AJ, Johnson J. Untapped reserves: controlling primordial follicle growth activation. Trends Mol Med 2018;24:319-31. https://doi.org/10.1016/j.molmed.2018.01.008

Cited by

  1. Development of Ovarian Tissue Autograft to Restore Ovarian Function: Protocol for a French Multicenter Cohort Study vol.8, pp.9, 2019, https://doi.org/10.2196/12944
  2. Sex-Dependent RNA Editing and N6 -adenosine RNA Methylation Profiling in the Gonads of a Fish, the Olive Flounder ( Paralichthys olivaceus ) vol.8, 2019, https://doi.org/10.3389/fcell.2020.00751
  3. The Factors and Pathways Regulating the Activation of Mammalian Primordial Follicles in vivo vol.8, 2020, https://doi.org/10.3389/fcell.2020.575706
  4. Hippo signaling, actin polymerization, and follicle activation in fragmented human ovarian cortex vol.87, pp.6, 2019, https://doi.org/10.1002/mrd.23353
  5. In vivo and in vitro activation of dormant primordial follicles by EGF treatment in mouse and human vol.10, pp.5, 2019, https://doi.org/10.1002/ctm2.182
  6. Premature ovarian insufficiency: an International Menopause Society White Paper vol.23, pp.5, 2019, https://doi.org/10.1080/13697137.2020.1804547
  7. In vitro activation of ovarian cortex and autologous transplantation: A novel approach to primary ovarian insufficiency and diminished ovarian reserve vol.2020, pp.4, 2020, https://doi.org/10.1093/hropen/hoaa046
  8. Rutin prevents cisplatin-induced ovarian damage via antioxidant activity and regulation of PTEN and FOXO3a phosphorylation in mouse model vol.98, 2019, https://doi.org/10.1016/j.reprotox.2020.10.001
  9. Synergistic effect of Huyang Yangkun Formula and embryonic stem cells on 4-vinylcyclohexene diepoxide induced premature ovarian insufficiency in mice vol.15, 2019, https://doi.org/10.1186/s13020-020-00362-6
  10. Primordial follicle survival of goat ovarian tissue after vitrification and transplantation on chorioallanthoic membrane vol.25, pp.1, 2020, https://doi.org/10.1186/s43043-020-00044-1
  11. Implications of Nonphysiological Ovarian Primordial Follicle Activation for Fertility Preservation vol.41, pp.6, 2019, https://doi.org/10.1210/endrev/bnaa020
  12. In Vitro Follicular Activation and Stem Cell Therapy as a Novel Treatment Strategies in Diminished Ovarian Reserve and Primary Ovarian Insufficiency vol.11, 2019, https://doi.org/10.3389/fendo.2020.617704
  13. Premature Ovarian Insufficiency: Past, Present, and Future vol.9, 2021, https://doi.org/10.3389/fcell.2021.672890
  14. In Vitro Folliculogenesis in Mammalian Models: A Computational Biology Study vol.8, 2019, https://doi.org/10.3389/fmolb.2021.737912
  15. Current mechanisms of primordial follicle activation and new strategies for fertility preservation vol.27, pp.2, 2019, https://doi.org/10.1093/molehr/gaab005
  16. A Prepubertal Mice Model to Study the Growth Pattern of Early Ovarian Follicles vol.22, pp.10, 2019, https://doi.org/10.3390/ijms22105130
  17. Phosphatidylinositol 3-Kinase δ-Specific Inhibitor-Induced Changes in the Ovary and Testis in the Sprague Dawley Rat and Cynomolgus Monkey vol.40, pp.4, 2019, https://doi.org/10.1177/10915818211008175
  18. Vitrification of canine ovarian tissue using the Ovarian Tissue Cryosystem (OTC) device vol.56, pp.8, 2021, https://doi.org/10.1111/rda.13979
  19. Novel approaches to fertility restoration in women with premature ovarian insufficiency vol.24, pp.5, 2019, https://doi.org/10.1080/13697137.2020.1856806
  20. Potential roles of experimental reproductive technologies in infertile women with diminished ovarian reserve vol.38, pp.10, 2019, https://doi.org/10.1007/s10815-021-02246-6
  21. Human BM-MSC secretome enhances human granulosa cell proliferation and steroidogenesis and restores ovarian function in primary ovarian insufficiency mouse model vol.11, pp.1, 2021, https://doi.org/10.1038/s41598-021-84216-7
  22. Comparative transcriptomic analysis of the different developmental stages of ovary in red swamp crayfish Procambarus clarkii vol.22, pp.1, 2019, https://doi.org/10.1186/s12864-021-07537-x