Clinical and Experimental Reproductive Medicine

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

DOI QR Code

Autophagy-related protein LC3 and Beclin-1 in the first trimester of pregnancy

  • Chifenti, Barbara (Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa Medical School) ;
  • Locci, Maria Teresa (Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa Medical School) ;
  • Lazzeri, Gloria (Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa Medical School) ;
  • Guagnozzi, Mariangela (Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa Medical School) ;
  • Dinucci, Dino (BIOlab, Department of Chemistry and Industrial Chemistry, University of Pisa) ;
  • Chiellini, Federica (BIOlab, Department of Chemistry and Industrial Chemistry, University of Pisa) ;
  • Filice, Maria Elena (Anatomy and Pathology Department, Section 2 Santa Chiara Hospital-University Health Care System) ;
  • Salerno, Maria Giovanna (Obstetrics and Gynecology Unit 2, Santa Chiara Hospital-University Health Care System) ;
  • Battini, Lorella (Obstetrics and Gynecology Unit 2, Santa Chiara Hospital-University Health Care System)
  • Received : 2012.11.23
  • Accepted : 2013.02.14
  • Published : 2013.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Autophagy is a degradation process that acts in response to environmental stressors. Recently, autophagy has been detected in normal term, preeclamptic and intrauterine growth-restricted placentas. The object of this work was to investigate the presence of autophagy in first trimester voluntary interruption of pregnancy placental villi by the expression of autophagy-related proteins, light chain 3 (LC3), and Beclin-1. In first trimester placental villi laser scanning confocal microscopy (LSCM) analysis revealed LC3 and Beclin-1 immunoreactivity prevalently located in villous cytotrophoblasts. Using LSCM, LC3, and Beclin-1 were localized to the cytoplasm of the trophoblast layer in human full-term placentas. Beclin-1 expression and LC3 activation were confirmed by western blotting. These data emphasize that autophagy activation is different among cytotrophoblasts and syncytiotrophoblasts depending on the gestational age and thus we speculate that autophagy might play a prosurvival role throughout human pregnancy.

Keywords

References

  1. Yang Z, Klionsky DJ. Eaten alive: a history of macroautophagy. Nat Cell Biol 2010;12:814-22. https://doi.org/10.1038/ncb0910-814
  2. Cecconi F, Levine B. The role of autophagy in mammalian development: cell makeover rather than cell death. Dev Cell 2008;15: 344-57. https://doi.org/10.1016/j.devcel.2008.08.012
  3. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000; 19:5720-8. https://doi.org/10.1093/emboj/19.21.5720
  4. Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, et al. Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol 1998;72:8586-96.
  5. Yue Z, Jin S, Yang C, Levine AJ, Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci U S A 2003;100: 15077-82. https://doi.org/10.1073/pnas.2436255100
  6. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999;402:672-6. https://doi.org/10.1038/45257
  7. Liu GH, Zhong Q, Ye YL, Wang HB, Hu LJ, Qin ZK, et al. Expression of beclin 1 in bladder cancer and its clinical significance. Int J Biol Markers 2012 Nov 5 [Epub]. http://dx.doi.org/10.5301/JBM.2012. 9769.
  8. Wirawan E, Lippens S, Vanden Berghe T, Romagnoli A, Fimia GM, Piacentini M, et al. Beclin1: a role in membrane dynamics and beyond. Autophagy 2012;8:6-17. https://doi.org/10.4161/auto.8.1.16645
  9. Huppertz B. The anatomy of the normal placenta. J Clin Pathol 2008;61:1296-302. https://doi.org/10.1136/jcp.2008.055277
  10. Signorelli P, Avagliano L, Virgili E, Gagliostro V, Doi P, Braidotti P, et al. Autophagy in term normal human placentas. Placenta 2011; 32:482-5. https://doi.org/10.1016/j.placenta.2011.03.005
  11. Oh SY, Choi SJ, Kim KH, Cho EY, Kim JH, Roh CR. Autophagy-related proteins, LC3 and Beclin-1, in placentas from pregnancies complicated by preeclampsia. Reprod Sci 2008;15:912-20. https://doi.org/10.1177/1933719108319159
  12. Curtis S, Jones CJ, Garrod A, Hulme CH, Heazell AE. Identification of autophagic vacuoles and regulators of autophagy in villous trophoblast from normal term pregnancies and in fetal growth restriction. J Matern Fetal Neonatal Med 2013;26:339-46. https://doi.org/10.3109/14767058.2012.733764
  13. Hung TH, Chen SF, Lo LM, Li MJ, Yeh YL, Hsieh TT. Increased autophagy in placentas of intrauterine growth-restricted pregnancies. PLoS One 2012;7:e40957. https://doi.org/10.1371/journal.pone.0040957
  14. Bildirici I, Longtine MS, Chen B, Nelson DM. Survival by self-destruction: a role for autophagy in the placenta? Placenta 2012; 33:591-8. https://doi.org/10.1016/j.placenta.2012.04.011

Cited by

  1. The checkpoint 1 kinase inhibitor LY2603618 induces cell cycle arrest, DNA damage response and autophagy in cancer cells vol.19, pp.9, 2013, https://doi.org/10.1007/s10495-014-1010-3
  2. The role of autophagy in the placenta as a regulator of cell death vol.41, pp.3, 2013, https://doi.org/10.5653/cerm.2014.41.3.97
  3. Oxidative Stress in Placenta: Health and Diseases vol.2015, pp.None, 2013, https://doi.org/10.1155/2015/293271
  4. Autophagy in Normal and Abnormal Early Human Pregnancies vol.22, pp.7, 2015, https://doi.org/10.1177/1933719114565036
  5. The Role of Secretory Autophagy in Zika Virus Transfer through the Placental Barrier vol.6, pp.None, 2013, https://doi.org/10.3389/fcimb.2016.00206
  6. miR-30e Blocks Autophagy and Acts Synergistically with Proanthocyanidin for Inhibition of AVEN and BIRC6 to Increase Apoptosis in Glioblastoma Stem Cells and Glioblastoma SNB19 Cells vol.11, pp.7, 2013, https://doi.org/10.1371/journal.pone.0158537
  7. Polysaccharide from Polygonatum Inhibits the Proliferation of Prostate Cancer-Associated Fibroblasts Cells vol.17, pp.8, 2013, https://doi.org/10.14456/apjcp.2016.177/apjcp.2016.17.8.3829
  8. Mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species-induced autophagic death vol.39, pp.6, 2013, https://doi.org/10.1177/1010428317711952
  9. Key Aging-Associated Alterations in Primary Microglia Response to Beta-Amyloid Stimulation vol.9, pp.None, 2013, https://doi.org/10.3389/fnagi.2017.00277
  10. Systematic Characterization of Autophagy in Gestational Diabetes Mellitus vol.158, pp.8, 2013, https://doi.org/10.1210/en.2016-1922
  11. The trophoblast survival capacity in preeclampsia vol.12, pp.11, 2013, https://doi.org/10.1371/journal.pone.0186909
  12. Autophagy and Cathepsin D mediated apoptosis contributing to ovarian follicular atresia in the Nile tilapia vol.86, pp.11, 2019, https://doi.org/10.1002/mrd.23245
  13. Anticancer Attributes of Cantharidin: Involved Molecular Mechanisms and Pathways vol.25, pp.14, 2013, https://doi.org/10.3390/molecules25143279
  14. Physiological and pathological regulation of autophagy in pregnancy vol.302, pp.2, 2013, https://doi.org/10.1007/s00404-020-05607-1
  15. Effects of an orally supplemented probiotic on the autophagy protein LC3 and Beclin1 in placentas undergoing spontaneous delivery during normal pregnancy vol.20, pp.1, 2013, https://doi.org/10.1186/s12884-020-02905-z
  16. Cell dynamics in human villous trophoblast vol.27, pp.5, 2021, https://doi.org/10.1093/humupd/dmab015
  17. Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury vol.16, pp.6, 2013, https://doi.org/10.4103/1673-5374.300725
  18. Treadmill Exercise Training Ameliorates Functional and Structural Age-Associated Kidney Changes in Male Albino Rats vol.2021, pp.None, 2021, https://doi.org/10.1155/2021/1393372
  19. The Effect and Mechanism of Asymmetric Dimethylarginine Regulating Trophoblastic Autophagy on Fetal Growth Restriction vol.28, pp.7, 2013, https://doi.org/10.1007/s43032-020-00442-w
  20. Codonopsis pilosula Extract Protects Melanocytes against H2O2-Induced Oxidative Stress by Activating Autophagy vol.8, pp.3, 2021, https://doi.org/10.3390/cosmetics8030067
  21. Dysregulated Autophagy Leads to Oxidative Stress and Aberrant Expression of ABC Transporters in Women with Early Miscarriage vol.10, pp.11, 2013, https://doi.org/10.3390/antiox10111742