Stem Cell Therapy in Premature Ovarian Failure

  • Susinder Sundaram
  • Paramasivam Nithyanand
  • Shaik Mohammad Naushad
  • Nikhita Kutala
  • Vijay Kumar Kutala


Premature ovarian failure (POF) occurs in women under the age of 40 years with primary or secondary hypergonadotropic amenorrhea and is accompanied by oestrogen deficiency in 75 % of cases. None of the women with primary amenorrhea have been reported to ovulate or conceive with their own oocytes, but more than a third of the women were pregnant at least once before developing hypergonadotropic POF.


Granulosa Cell Premature Ovarian Failure Ovarian Surface Epithelium Germ Line Stem Cell Atretic Follicle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Bukovsky A (2006) Oogenesis from human somatic stem cells and a role of immune adaptation in premature ovarian failure. Curr Stem Cell Res Ther 1(3):289–303PubMedCrossRefGoogle Scholar
  2. 2.
    Bukovsky A, Ayala ME, Dominguez R, Keenan JA, Wimalasena J, Elder RF, Caudle MR (2002) Changes of ovarian interstitial cell hormone receptors and behavior of resident mesenchymal cells in developing and adult rats with steroid-induced sterility. Steroids 67(3–4):277–289PubMedCrossRefGoogle Scholar
  3. 3.
    Bukovsky A, Svetlikova M, Caudle MR (2005) Oogenesis in cultures derived from adult human ovaries. Reprod Biol Endocrinol 3:17PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Beagley KW, Husband AJ (1998) Intraepithelial lymphocytes: origins, distribution, and function. Crit Rev Immunol 18:237–254PubMedCrossRefGoogle Scholar
  5. 5.
    Doherty PC, Topham DJ, Tripp RA, Cardin RD, Brooks JW, Stevenson PG (1997) Effector CD4+ and CD8+ T-cell mechanisms in the control of respiratory virus infections. Immunol Rev 159:105–117PubMedCrossRefGoogle Scholar
  6. 6.
    Giglio T, Imro MA, Filaci G et al (1994) Immune cell circulating subsets are affected by gonadal function. Life Sci 54:1305–1312PubMedCrossRefGoogle Scholar
  7. 7.
    Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL (2004) Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428(6979):145–150PubMedCrossRefGoogle Scholar
  8. 8.
    Johnson J, Bagley J, Skaznik-Wikiel M, Lee HJ, Adams GB, Niikura Y, Tschudy KS, Tilly JC, Cortes ML, Forkert R, Spitzer T, Iacomini J, Scadden DT, Tilly JL (2005) Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell 122(2):303–315PubMedCrossRefGoogle Scholar
  9. 9.
    Shiromizu K, Thorgeirsson SS, Mattison DR (1984) Effect of cyclophosphamide on oocyte and follicle number in Sprague-Dawley rats, C57BL/6 N and DBA/2 N mice. Pediatr Pharmacol (New York) 4(4):213–221Google Scholar
  10. 10.
    Zou K, Yuan Z, Yang Z, Luo H, Sun K, Zhou L, Xiang J, Shi L, Yu Q, Zhang Y, Hou R, Wu J (2009) Production of offspring from a germline stem cell line derived from neonatal ovaries. Nat Cell Biol 11(5):631–636PubMedCrossRefGoogle Scholar
  11. 11.
    Kirilly D, Xie T (2007) The Drosophila ovary: an active stem cell community. Cell Res 17(1):15–25PubMedCrossRefGoogle Scholar
  12. 12.
    Nakamura S, Kobayashi K, Nishimura T, Tanaka M (2011) Ovarian germline stem cells in the teleost fish, medaka (Oryzias latipes). Int J Biol Sci 7(4):403–409PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Pacchiarotti J, Maki C, Ramos T, Marh J, Howerton K, Wong J, Pham J, Anorve S, Chow YC, Izadyar F (1984) Differentiation potential of germ line stem cells derived from the postnatal mouse ovary. Pediatr Pharmacol (New York) 4(4):213–221Google Scholar
  14. 14.
    Reynier P, May-Panloup P, Chrétien MF, Morgan CJ, Jean M, Savagner F, Barrière P, Malthièry Y (2001) Mitochondrial DNA content affects the fertilizability of human oocytes. Mol Hum Reprod 7(5):425–429PubMedCrossRefGoogle Scholar
  15. 15.
    May-Panloup P, Chrétien MF, Jacques C, Vasseur C, Malthièry Y, Reynier P (2005) Low oocyte mitochondrial DNA content in ovarian insufficiency. Hum Reprod 20(3):593–597PubMedCrossRefGoogle Scholar
  16. 16.
    Larsson NG, Wang J, Wilhelmsson H, Oldfors A, Rustin P, Lewandoski M, Barsh GS, Clayton DA (1998) Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet 18(3):231–236PubMedCrossRefGoogle Scholar
  17. 17.
    Cohen J, Scott R, Alikani M, Schimmel T, Munné S, Levron J, Wu L, Brenner C, Warner C, Willadsen S (1998) Ooplasmic transfer in mature human oocytes. Mol Hum Reprod 4(3):269–280PubMedCrossRefGoogle Scholar
  18. 18.
    Barritt JA, Brenner CA, Malter HE, Cohen J (2001) Mitochondria in human offspring derived from ooplasmic transplantation. Hum Reprod 16(3):513–516PubMedCrossRefGoogle Scholar
  19. 19.
    Barritt J, Willadsen S, Brenner C, Cohen J (2001) Cytoplasmic transfer in assisted reproduction. Hum Reprod Update 7(4):428–435PubMedCrossRefGoogle Scholar
  20. 20.
    Harvey AJ, Gibson TC, Quebedeaux TM, Brenner CA (2007) Impact of assisted reproductive technologies: a mitochondrial perspective of cytoplasmic transplantation. Curr Top Dev Biol 77:229–249PubMedCrossRefGoogle Scholar
  21. 21.
    Acton BM, Lai I, Shang X, Jurisicova A, Casper RF (2007) Neutral mitochondrial heteroplasmy alters physiological function in mice. Biol Reprod 77(3):569–576PubMedCrossRefGoogle Scholar
  22. 22.
    White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL (2012) Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med 18(3):413–421PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Hao J, Zhu W, Sheng C et al (2009) Human parthenogenetic embryonic stem cells: one potential resource for cell therapy. Sci China C Life Sci 52:599–602PubMedCrossRefGoogle Scholar
  24. 24.
    Taupin P (2006) Autologous transplantation in the central nervous system. Indian J Med Res 124:613–618PubMedGoogle Scholar
  25. 25.
    Pashaiasl M, Khodadadi K, Holland MK et al (2010) The efficient generation of cell lines from bovine parthenotes. Cell Reprogram 12:571–579PubMedCrossRefGoogle Scholar
  26. 26.
    Surani MA, Barton SC (1983) Development of gynogenetic eggs in the mouse: implications for parthenogenetic embryos. Science 222(4627):1034–1036PubMedCrossRefGoogle Scholar
  27. 27.
    Imesch P, Scheiner D, Xie M, Fink D, Macas E, Dubey R, Imthurn B (2013) Developmental potential of human oocytes matured in vitro followed by vitrification and activation. J Ovarian Res 6(1):30PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    McGrath J, Solter D (1984) Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37(1):179–183PubMedCrossRefGoogle Scholar
  29. 29.
    Blumenfeld Z, Eckman A (2005) Preservation of fertility and ovarian function and minimization of chemotherapy-induced gonadotoxicity in young women by GnRH-a. J Natl Cancer Inst Monogr 34:40–43PubMedCrossRefGoogle Scholar
  30. 30.
    Del Mastro L, Boni L, Michelotti A, Gamucci T, Olmeo N, Gori S, Giordano M, Garrone O, Pronzato P, Bighin C, Levaggi A, Giraudi S, Cresti N, Magnolfi E, Scotto T, Vecchio C, Venturini M (2011) Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial. JAMA 306(3):269–276PubMedGoogle Scholar
  31. 31.
    Lee HJ, Selesniemi K, Niikura Y, Niikura T, Klein R, Dombkowski DM, Tilly JL (2007) Bone marrow transplantation generates immature oocytes and rescues long-term fertility in a preclinical mouse model of chemotherapy-induced premature ovarian failure. J Clin Oncol 25(22):3198–3204PubMedCrossRefGoogle Scholar
  32. 32.
    Wang F, Wang L, Yao X, Lai D, Guo L (2013) Human amniotic epithelial cells can differentiate into granulosa cells and restore folliculogenesis in a mouse model of chemotherapy-induced premature ovarian failure. Stem Cell Res Ther 4(5):124PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Visser JA, de Jong FH, Laven JS, Themmen AP (2006) Anti-Müllerian hormone: a new marker for ovarian function. Reproduction 131(1):1–9PubMedCrossRefGoogle Scholar
  34. 34.
    Hübner K, Fuhrmann G, Christenson LK, Kehler J, Reinbold R, De La Fuente R, Wood J, Strauss JF 3rd, Boiani M, Schöler HR (2003) Derivation of oocytes from mouse embryonic stem cells. Science 300(5623):1251–1256PubMedCrossRefGoogle Scholar
  35. 35.
    Qing T, Shi Y, Qin H, Ye X, Wei W, Liu H, Ding M, Deng H (2007) Induction of oocyte-like cells from mouse embryonic stem cells by co-culture with ovarian granulosa cells. Differentiation 75(10):902–911PubMedGoogle Scholar
  36. 36.
    Woods DC, White YA, Niikura Y, Kiatpongsan S, Lee HJ, Tilly JL (2013) Embryonic stem cell-derived granulosa cells participate in ovarian follicle formation in vitro and in vivo. Reprod Sci 20(5):524–535PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Schmidt D, Ovitt CE, Anlag K, Fehsenfeld S, Gredsted L, Treier AC, Treier M (2004) The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance. Development 131(4):933–942PubMedCrossRefGoogle Scholar
  38. 38.
    Nicholas CR, Haston KM, Grewall AK, Longacre TA, Reijo Pera RA (2009) Transplantation directs oocyte maturation from embryonic stem cells and provides a therapeutic strategy for female infertility. Hum Mol Genet 18(22):4376–4389PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Gimble JM, Katz AJ, Bunnell BA (2007) Adipose-derived stem cells for regenerative medicine. Circ Res 100(9):1249–1260PubMedCrossRefGoogle Scholar
  40. 40.
    Sun M, Wang S, Li Y, Yu L, Gu F, Wang C, Yao Y (2013) Adipose-derived stem cells improved mouse ovary function after chemotherapy-induced ovary failure. Stem Cell Res Ther 4(4):80PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Liu T, Zou G, Gao Y, Zhao X, Wang H, Huang Q, Jiang L, Guo L, Cheng W (2012) High efficiency of reprogramming CD34+ cells derived from human amniotic fluid into induced pluripotent stem cells with Oct4. Stem Cells Dev 21(12):2322–2332PubMedCrossRefGoogle Scholar
  42. 42.
    Rappolee DA, Sturm KS, Behrendtsen O, Schultz GA, Pedersen RA, Werb Z (1992) Insulin-like growth factor II acts through an endogenous growth pathway regulated by imprinting in early mouse embryos. Genes Dev 6(6):939–952PubMedCrossRefGoogle Scholar
  43. 43.
    Penkov LI, Platonov ES, New DA (2001) Effects of fibroblast growth factor 2 and insulin-like growth factor II on the development of parthenogenetic mouse embryos in vitro. In Vitro Cell Dev Biol Anim 37(7):440–444PubMedCrossRefGoogle Scholar
  44. 44.
    Platonov ES (2005) Genomic imprinting and problem of parthenogenesis in mammals. Ontogenez 36(4):300–309PubMedGoogle Scholar
  45. 45.
    Lei L, Zhang H, Jin S, Wang F, Fu M, Wang H, Xia G (2006) Stage-specific germ-somatic cell interaction directs the primordial folliculogenesis in mouse fetal ovaries. J Cell Physiol 208(3):640–647PubMedCrossRefGoogle Scholar

Copyright information

© Springer India 2014

Authors and Affiliations

  • Susinder Sundaram
    • 1
  • Paramasivam Nithyanand
    • 1
  • Shaik Mohammad Naushad
    • 1
  • Nikhita Kutala
    • 2
  • Vijay Kumar Kutala
    • 3
  1. 1.School of Chemical & BiotechnologySASTRA UniversityThanjavurIndia
  2. 2.SVS Institute of Dental SciencesMahabubnagarIndia
  3. 3.Department of Clinical Pharmacology and TherapeuticsNizam’s Institute of Medical SciencesHyderabadIndia

Personalised recommendations