Skip to main content

Advertisement

Log in

Roles of the Notch Signaling Pathway in Ovarian Functioning

  • Review
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

A Correction to this article was published on 12 July 2021

This article has been updated

Abstract

The Notch signaling pathway regulates cell invasion, adhesion, proliferation, apoptosis, and differentiation via cell-to-cell interactions and plays important physiological roles in the ovary. This review summarizes current knowledge about the Notch signaling pathway in relation to ovarian functions and reveals the potential underlying mechanisms. We conducted an in-depth review of relevant literature to determine the current status of research into the Notch signaling pathway in relation to ovarian functioning and reveal potential underlying mechanisms. The activation of different Notch receptors promotes the formation of primordial follicles and proliferation of granulosa cells and inhibits steroid secretion. Abnormal regulation of the Notch signaling pathway or direct mutations might lead to over-activation or under-activation of the receptors, resulting in Notch upregulation or downregulation. It can also disrupt the normal physiological functions of the ovary. The lncRNA HOTAIR and growth hormones improved premature ovarian failure (POF) and promoted follicle maturation in a mouse model of POF by upregulating Notch1 expression. They also stimulated the Notch1 signaling pathway, increased the level of plasma estradiol, and decreased the level of plasma follicle-stimulating hormone. Thus, Notch1 could serve as a novel therapeutic target for POF. Several studies have reported multiple roles of Notch in regulating female primordial follicle formation and follicle maturation. Direct mutations in Notch-related molecules or abnormal gene regulation in the signaling pathway can lead to ovarian dysfunction. However, the underlying mechanisms are not fully understood.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Change history

References

  1. Egan SE, St-Pierre B, Leow CC. Notch receptors, partners and regulators: from conserved domains to powerful functions. Curr Top Microbiol Immunol. 1998;228:273–324. https://doi.org/10.1007/978-3-642-80481-6_11.

    Article  CAS  PubMed  Google Scholar 

  2. Schroeter EH, Kisslinger JA, Kopan R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature. 1998;393(6683):382–6. https://doi.org/10.1038/30756.

    Article  CAS  PubMed  Google Scholar 

  3. Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999;284(5415):770–6. https://doi.org/10.1126/science.284.5415.770.

    Article  CAS  PubMed  Google Scholar 

  4. Bray SJ. Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006;7(9):678–89. https://doi.org/10.1038/nrm2009.

    Article  CAS  PubMed  Google Scholar 

  5. Leong KG, Karsan A. Recent insights into the role of Notch signaling in tumorigenesis. Blood. 2006;107(6):2223–33. https://doi.org/10.1182/blood-2005-08-3329.

    Article  CAS  PubMed  Google Scholar 

  6. Siebel C, Lendahl U. Notch signaling in development, tissue homeostasis, and disease. Physiol Rev. 2017;97(4):1235–94. https://doi.org/10.1152/physrev.00005.2017.

    Article  CAS  PubMed  Google Scholar 

  7. Ayaz F, Osborne BA. Non-canonical notch signaling in cancer and immunity. Front Oncol. 2014;4:345. https://doi.org/10.3389/fonc.2014.00345.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Suresh S, Irvine AE. The NOTCH signaling pathway in normal and malignant blood cell production. J Cell Commun Signal. 2015;9(1):5–13. https://doi.org/10.1007/s12079-015-0271-0.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Chillakuri CR, Sheppard D, Lea SM, Handford PA. Notch receptor-ligand binding and activation: insights from molecular studies. Semin Cell Dev Biol. 2012;23(4):421–8. https://doi.org/10.1016/j.semcdb.2012.01.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fiuza UM, Arias AM. Cell and molecular biology of Notch. J Endocrinol. 2007;194(3):459–74. https://doi.org/10.1677/JOE-07-0242.

    Article  CAS  PubMed  Google Scholar 

  11. Kopan R, Ilagan MX. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009;137(2):216–33. https://doi.org/10.1016/j.cell.2009.03.045.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cave JW. Selective repression of Notch pathway target gene transcription. Dev Biol. 2011;360(1):123–31. https://doi.org/10.1016/j.ydbio.2011.09.018.

    Article  CAS  PubMed  Google Scholar 

  13. Bray SJ. Notch signalling in context. Nat Rev Mol Cell Biol. 2016;17(11):722–35. https://doi.org/10.1038/nrm.2016.94.

    Article  CAS  PubMed  Google Scholar 

  14. Nandagopal N, Santat LA, LeBon L, Sprinzak D, Bronner ME, Elowitz MB. Dynamic ligand discrimination in the Notch signaling pathway. Cell. 2018;172(4):869–80 e819. https://doi.org/10.1016/j.cell.2018.01.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zanotti S, Canalis E. Notch signaling and the skeleton. Endocr Rev. 2016;37(3):223–53. https://doi.org/10.1210/er.2016-1002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang H, Zang C, Liu XS, Aster JC. The role of Notch receptors in transcriptional regulation. J Cell Physiol. 2015;230(5):982–8. https://doi.org/10.1002/jcp.24872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Andersen P, Uosaki H, Shenje LT, Kwon C. Non-canonical Notch signaling: emerging role and mechanism. Trends Cell Biol. 2012;22(5):257–65. https://doi.org/10.1016/j.tcb.2012.02.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Deng WM, Bownes M. Patterning and morphogenesis of the follicle cell epithelium during Drosophila oogenesis. Int J Dev Biol. 1998;42(4):541–52.

    CAS  PubMed  Google Scholar 

  19. Edgar BA, Orr-Weaver TL. Endoreplication cell cycles: more for less. Cell. 2001;105(3):297–306. https://doi.org/10.1016/s0092-8674(01)00334-8.

    Article  CAS  PubMed  Google Scholar 

  20. Deng WM, Althauser C, Ruohola-Baker H. Notch-Delta signaling induces a transition from mitotic cell cycle to endocycle in Drosophila follicle cells. Development. 2001;128(23):4737–46.

    Article  CAS  PubMed  Google Scholar 

  21. Lopez-Schier H, St Johnston D. Delta signaling from the germ line controls the proliferation and differentiation of the somatic follicle cells during Drosophila oogenesis. Genes Dev. 2001;15(11):1393–405. https://doi.org/10.1101/gad.200901.

    Article  CAS  PubMed  Google Scholar 

  22. Murta D, Batista M, Silva E, Trindade A, Mateus L, Duarte A, et al. Differential expression of Notch component and effector genes during ovarian follicle and corpus luteum development during the oestrous cycle. Reprod Fertil Dev. 2015;27(7):1038–48. https://doi.org/10.1071/RD13399.

    Article  CAS  PubMed  Google Scholar 

  23. Feng YM, Liang GJ, Pan B, Qin XS, Zhang XF, Chen CL, et al. Notch pathway regulates female germ cell meiosis progression and early oogenesis events in fetal mouse. Cell Cycle. 2014;13(5):782–91. https://doi.org/10.4161/cc.27708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pepling ME, Spradling AC. Female mouse germ cells form synchronously dividing cysts. Development. 1998;125(17):3323–8.

    Article  CAS  PubMed  Google Scholar 

  25. Epifano O, Dean J. Genetic control of early folliculogenesis in mice. Trends Endocrinol Metab. 2002;13(4):169–73. https://doi.org/10.1016/s1043-2760(02)00576-3.

    Article  CAS  PubMed  Google Scholar 

  26. Jagarlamudi K, Rajkovic A. Oogenesis: transcriptional regulators and mouse models. Mol Cell Endocrinol. 2012;356(1-2):31–9. https://doi.org/10.1016/j.mce.2011.07.049.

    Article  CAS  PubMed  Google Scholar 

  27. Pepling ME. Follicular assembly: mechanisms of action. Reproduction. 2012;143(2):139–49. https://doi.org/10.1530/REP-11-0299.

    Article  CAS  PubMed  Google Scholar 

  28. Tingen C, Kim A, Woodruff TK. The primordial pool of follicles and nest breakdown in mammalian ovaries. Mol Hum Reprod. 2009;15(12):795–803. https://doi.org/10.1093/molehr/gap073.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Johnson J, Espinoza T, McGaughey RW, Rawls A, Wilson-Rawls J. Notch pathway genes are expressed in mammalian ovarian follicles. Mech Dev. 2001;109(2):355–61. https://doi.org/10.1016/s0925-4773(01)00523-8.

    Article  CAS  PubMed  Google Scholar 

  30. Trombly DJ, Woodruff TK, Mayo KE. Suppression of Notch signaling in the neonatal mouse ovary decreases primordial follicle formation. Endocrinology. 2009;150(2):1014–24. https://doi.org/10.1210/en.2008-0213.

    Article  CAS  PubMed  Google Scholar 

  31. Zhang CP, Yang JL, Zhang J, Li L, Huang L, Ji SY, et al. Notch signaling is involved in ovarian follicle development by regulating granulosa cell proliferation. Endocrinology. 2011;152(6):2437–47. https://doi.org/10.1210/en.2010-1182.

    Article  CAS  PubMed  Google Scholar 

  32. Feng L, Wang Y, Cai H, Sun G, Niu W, Xin Q, et al. ADAM10-Notch signaling governs the recruitment of ovarian pregranulosa cells and controls folliculogenesis in mice. J Cell Sci. 2016;129(11):2202–12. https://doi.org/10.1242/jcs.184267.

    Article  CAS  PubMed  Google Scholar 

  33. Wang LQ, Liu JC, Chen CL, Cheng SF, Sun XF, Zhao Y, et al. Regulation of primordial follicle recruitment by cross-talk between the Notch and phosphatase and tensin homologue (PTEN)/AKT pathways. Reprod Fertil Dev. 2016;28(6):700–12. https://doi.org/10.1071/RD14212.

    Article  CAS  PubMed  Google Scholar 

  34. Terauchi KJ, Shigeta Y, Iguchi T, Sato T. Role of Notch signaling in granulosa cell proliferation and polyovular follicle induction during folliculogenesis in mouse ovary. Cell Tissue Res. 2016;365(1):197–208. https://doi.org/10.1007/s00441-016-2371-4.

    Article  CAS  PubMed  Google Scholar 

  35. Xu J, Gridley T. Notch2 is required in somatic cells for breakdown of ovarian germ-cell nests and formation of primordial follicles. BMC Biol. 2013;11:13. https://doi.org/10.1186/1741-7007-11-13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhao L, Du X, Huang K, Zhang T, Teng Z, Niu W, et al. Rac1 modulates the formation of primordial follicles by facilitating STAT3-directed Jagged1, GDF9 and BMP15 transcription in mice. Sci Rep. 2016;6:23972. https://doi.org/10.1038/srep23972.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Vanorny DA, Prasasya RD, Chalpe AJ, Kilen SM, Mayo KE. Notch signaling regulates ovarian follicle formation and coordinates follicular growth. Mol Endocrinol. 2014;28(4):499–511. https://doi.org/10.1210/me.2013-1288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. George RM, Hahn KL, Rawls A, Viger RS, Wilson-Rawls J. Notch signaling represses GATA4-induced expression of genes involved in steroid biosynthesis. Reproduction. 2015;150(4):383–94. https://doi.org/10.1530/REP-15-0226.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kwintkiewicz J, Cai Z, Stocco C. Follicle-stimulating hormone-induced activation of Gata4 contributes in the up-regulation of Cyp19 expression in rat granulosa cells. Mol Endocrinol. 2007;21(4):933–47. https://doi.org/10.1210/me.2006-0446.

    Article  CAS  PubMed  Google Scholar 

  40. Robker RL, Richards JS. Hormonal control of the cell cycle in ovarian cells: proliferation versus differentiation. Biol Reprod. 1998;59(3):476–82. https://doi.org/10.1095/biolreprod59.3.476.

    Article  CAS  PubMed  Google Scholar 

  41. Prasasya RD, Mayo KE. Notch signaling regulates differentiation and steroidogenesis in female mouse ovarian granulosa cells. Endocrinology. 2018;159(1):184–98. https://doi.org/10.1210/en.2017-00677.

    Article  CAS  PubMed  Google Scholar 

  42. Hubbard N, Prasasya RD, Mayo KE. Activation of Notch signaling by oocytes and Jag1 in mouse ovarian granulosa cells. Endocrinology. 2019;160(12):2863–76. https://doi.org/10.1210/en.2019-00564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004;428(6979):145–50. https://doi.org/10.1038/nature02316.

    Article  CAS  PubMed  Google Scholar 

  44. Bukovsky A. Cell commitment by asymmetric division and immune system involvement. Prog Mol Subcell Biol. 2007;45:179–204. https://doi.org/10.1007/978-3-540-69161-7_8.

    Article  CAS  PubMed  Google Scholar 

  45. Pan Z, Sun M, Li J, Zhou F, Liang X, Huang J, et al. The expression of markers related to ovarian germline stem cells in the mouse ovarian surface epithelium and the correlation with Notch signaling pathway. Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology. 2015;37(6):2311–22. https://doi.org/10.1159/000438586.

    Article  CAS  Google Scholar 

  46. Ye H, Li X, Zheng T, Hu C, Pan Z, Huang J, et al. The Hippo signaling pathway regulates ovarian function via the proliferation of ovarian germline stem cells. Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology. 2017;41(3):1051–62. https://doi.org/10.1159/000464113.

    Article  CAS  Google Scholar 

  47. Ng CL, Qian Y, Schulz C. Notch and Delta are required for survival of the germline stem cell lineage in testes of Drosophila melanogaster. PLoS One. 2019;14(9):e0222471. https://doi.org/10.1371/journal.pone.0222471.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Tseng CY, Kao SH, Wan CL, Cho Y, Tung SY, Hsu HJ. Notch signaling mediates the age-associated decrease in adhesion of germline stem cells to the niche. PLoS Genet. 2014;10(12):e1004888. https://doi.org/10.1371/journal.pgen.1004888.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Bonfini A, Wilkin MB, Baron M. Reversible regulation of stem cell niche size associated with dietary control of Notch signalling. BMC Dev Biol. 2015;15:8. https://doi.org/10.1186/s12861-015-0059-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lobo-Pecellín M, Marín-Menguiano M, González-Reyes A. Mastermind regulates niche ageing independently of the Notch pathway in the Drosophila ovary. Open Biol. 2019;9(11):190127. https://doi.org/10.1098/rsob.190127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Hsu HJ, Drummond-Barbosa D. Insulin signals control the competence of the Drosophila female germline stem cell niche to respond to Notch ligands. Dev Biol. 2011;350(2):290–300. https://doi.org/10.1016/j.ydbio.2010.11.032.

    Article  CAS  PubMed  Google Scholar 

  52. Li D, Li C, Xu Y, Xu D, Li H, Gao L, et al. Differential expression of microRNAs in the ovaries from letrozole-induced rat model of polycystic ovary syndrome. DNA Cell Biol. 2016;35(4):177–83. https://doi.org/10.1089/dna.2015.3145.

    Article  CAS  PubMed  Google Scholar 

  53. Grazul-Bilska AT, Redmer DA, Reynolds LP. Cellular interactions in the corpus luteum. Semin Reprod Endocrinol. 1997;15(4):383–93. https://doi.org/10.1055/s-2008-1068376.

    Article  CAS  PubMed  Google Scholar 

  54. Peng J, Tang M, Zhang BP, Zhang P, Zhong T, Zong T, et al. Kisspeptin stimulates progesterone secretion via the Erk1/2 mitogen-activated protein kinase signaling pathway in rat luteal cells. Fertil Steril. 2013;99(5):1436–43 e1431. https://doi.org/10.1016/j.fertnstert.2012.12.008.

    Article  CAS  PubMed  Google Scholar 

  55. Stocco C, Telleria C, Gibori G. The molecular control of corpus luteum formation, function, and regression. Endocr Rev. 2007;28(1):117–49. https://doi.org/10.1210/er.2006-0022.

    Article  CAS  PubMed  Google Scholar 

  56. Fraser HM, Hastings JM, Allan D, Morris KD, Rudge JS, Wiegand SJ. Inhibition of delta-like ligand 4 induces luteal hypervascularization followed by functional and structural luteolysis in the primate ovary. Endocrinology. 2012;153(4):1972–83. https://doi.org/10.1210/en.2011-1688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Garcia-Pascual CM, Zimmermann RC, Ferrero H, Shawber CJ, Kitajewski J, Simon C, et al. Delta-like ligand 4 regulates vascular endothelial growth factor receptor 2-driven luteal angiogenesis through induction of a tip/stalk phenotype in proliferating endothelial cells. Fertil Steril. 2013;100(6):1768–76 e1761. https://doi.org/10.1016/j.fertnstert.2013.08.034.

    Article  CAS  PubMed  Google Scholar 

  58. Hahlin M, Dennefors B, Johanson C, Hamberger L. Luteotropic effects of prostaglandin E2 on the human corpus luteum of the menstrual cycle and early pregnancy. J Clin Endocrinol Metab. 1988;66(5):909–14. https://doi.org/10.1210/jcem-66-5-909.

    Article  CAS  PubMed  Google Scholar 

  59. Hashii K, Fujiwara H, Yoshioka S, Kataoka N, Yamada S, Hirano T, et al. Peripheral blood mononuclear cells stimulate progesterone production by luteal cells derived from pregnant and non-pregnant women: possible involvement of interleukin-4 and interleukin-10 in corpus luteum function and differentiation. Hum Reprod. 1998;13(1O):2738–44. https://doi.org/10.1093/humrep/13.10.2738.

    Article  CAS  PubMed  Google Scholar 

  60. Niswender GD, Juengel JL, Silva PJ, Rollyson MK, McIntush EW. Mechanisms controlling the function and life span of the corpus luteum. Physiol Rev. 2000;80(1):1–29. https://doi.org/10.1152/physrev.2000.80.1.1.

    Article  CAS  PubMed  Google Scholar 

  61. White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med. 2012;18(3):413–21. https://doi.org/10.1038/nm.2669.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bothun AM, Gao Y, Takai Y, Ishihara O, Seki H, Karger B, et al. Quantitative proteomic profiling of the human ovary from early to mid-gestation reveals protein expression dynamics of oogenesis and folliculogenesis. Stem Cells Dev. 2018;27(11):723–35. https://doi.org/10.1089/scd.2018.0002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Silvestris E, Cafforio P, D'Oronzo S, Felici C, Silvestris F, Loverro G. In vitro differentiation of human oocyte-like cells from oogonial stem cells: single-cell isolation and molecular characterization. Hum Reprod. 2018;33(3):464–73. https://doi.org/10.1093/humrep/dex377.

    Article  CAS  PubMed  Google Scholar 

  64. Auletta FJ, Flint AP. Mechanisms controlling corpus luteum function in sheep, cows, nonhuman primates, and women especially in relation to the time of luteolysis. Endocr Rev. 1988;9(1):88–105. https://doi.org/10.1210/edrv-9-1-88.

    Article  CAS  PubMed  Google Scholar 

  65. Niswender GD, Juengel JL, McGuire WJ, Belfiore CJ, Wiltbank MC. Luteal function: the estrous cycle and early pregnancy. Biol Reprod. 1994;50(2):239–47. https://doi.org/10.1095/biolreprod50.2.239.

    Article  CAS  PubMed  Google Scholar 

  66. Care AS, Diener KR, Jasper MJ, Brown HM, Ingman WV, Robertson SA. Macrophages regulate corpus luteum development during embryo implantation in mice. J Clin Invest. 2013;123(8):3472–87. https://doi.org/10.1172/JCI60561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Accialini P, Hernandez SF, Bas D, Pazos MC, Irusta G, Abramovich D, et al. A link between Notch and progesterone maintains the functionality of the rat corpus luteum. Reproduction. 2015;149(1):1–10. https://doi.org/10.1530/REP-14-0449.

    Article  CAS  PubMed  Google Scholar 

  68. Wang J, Liu S, Peng L, Dong Q, Bao R, Lv Q, et al. Notch signaling pathway regulates progesterone secretion in murine luteal cells. Reprod Sci. 2015;22(10):1243–51. https://doi.org/10.1177/1933719115572480.

    Article  CAS  PubMed  Google Scholar 

  69. Wang Y, Lu E, Bao R, Xu P, Feng F, Wen W, et al. Notch signalling regulates steroidogenesis in mouse ovarian granulosa cells. Reprod Fertil Dev. 2019;31(6):1091–103. https://doi.org/10.1071/RD18281.

    Article  CAS  PubMed  Google Scholar 

  70. Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS, Legro RS. Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr Rev. 2015;36(5):487–525. https://doi.org/10.1210/er.2015-1018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Risal S, Pei Y, Lu H, Manti M, Fornes R, Pui HP, et al. Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome. Nat Med. 2019;25(12):1894–904. https://doi.org/10.1038/s41591-019-0666-1.

    Article  CAS  PubMed  Google Scholar 

  72. Jayasena CN, Franks S. The management of patients with polycystic ovary syndrome. Nat Rev Endocrinol. 2014;10(10):624–36. https://doi.org/10.1038/nrendo.2014.102.

    Article  PubMed  Google Scholar 

  73. Xu B, Zhang YW, Tong XH, Liu YS. Characterization of microRNA profile in human cumulus granulosa cells: identification of microRNAs that regulate Notch signaling and are associated with PCOS. Mol Cell Endocrinol. 2015;404(C):26–36. https://doi.org/10.1016/j.mce.2015.01.030.

    Article  CAS  PubMed  Google Scholar 

  74. Yang D, Li N, Ma A, Dai F, Zheng Y, Hu X, et al. Identification of potential biomarkers of polycystic ovary syndrome via integrated bioinformatics analysis. Reprod Sci. 2020;28:1353–61. https://doi.org/10.1007/s43032-020-00352-x.

    Article  CAS  PubMed  Google Scholar 

  75. Han Q, Zhang W, Meng J, Ma L, Li A. LncRNA-LET inhibits cell viability, migration and EMT while induces apoptosis by up-regulation of TIMP2 in human granulosa-like tumor cell line KGN. Biomed Pharmacother. 2018;100:250–6. https://doi.org/10.1016/j.biopha.2018.01.162.

    Article  CAS  PubMed  Google Scholar 

  76. Palomba S, Daolio J, La Sala GB. Oocyte competence in women with polycystic ovary syndrome. Trends Endocrinol Metab. 2017;28(3):186–98. https://doi.org/10.1016/j.tem.2016.11.008.

    Article  CAS  PubMed  Google Scholar 

  77. Xie Q, Cheng Z, Chen X, Lobe CG, Liu J. The role of Notch signalling in ovarian angiogenesis. J Ovarian Res. 2017;10(1):13. https://doi.org/10.1186/s13048-017-0308-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. European Society for Human R, Embryology 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(5):926–37. https://doi.org/10.1093/humrep/dew027.

    Article  Google Scholar 

  79. Patino LC, Beau I, Morel A, Delemer B, Young J, Binart N, et al. Functional evidence implicating NOTCH2 missense mutations in primary ovarian insufficiency etiology. Hum Mutat. 2019;40(1):25–30. https://doi.org/10.1002/humu.23667.

    Article  CAS  PubMed  Google Scholar 

  80. Li L, Feng F, Zhao M, Li T, Yue W, Ma X, et al. NOTCH2 variant D1853H is mutated in two non-syndromic premature ovarian insufficiency patients from a Chinese pedigree. J Ovarian Res. 2020;13(1):41. https://doi.org/10.1186/s13048-020-00645-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Liu TE, Wang S, Zhang L, Guo L, Yu Z, Chen C, et al. Growth hormone treatment of premature ovarian failure in a mouse model via stimulation of the Notch-1 signaling pathway. Exp Ther Med. 2016;12(1):215–21. https://doi.org/10.3892/etm.2016.3326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Zhao W, Dong L. Long non-coding RNA HOTAIR overexpression improves premature ovarian failure by upregulating Notch-1 expression. Exp Ther Med. 2018;16(6):4791–5. https://doi.org/10.3892/etm.2018.6750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Availability of Data and Materials

Not applicable.

Code Availability

Not applicable.

Funding

This work was funded by the National Key Research and Development Project (2018YFC1004400).

Author information

Authors and Affiliations

Authors

Contributions

SH Guo: Project development, literature search, and manuscript writing. S Quan: Manuscript editing. SY Zou: Literature search and manuscript writing.

Corresponding author

Correspondence to Song Quan.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, S., Quan, S. & Zou, S. Roles of the Notch Signaling Pathway in Ovarian Functioning. Reprod. Sci. 28, 2770–2778 (2021). https://doi.org/10.1007/s43032-021-00610-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-021-00610-6

Keywords

Navigation