Skip to main content

Advertisement

Log in

Physiological and pathological regulation of autophagy in pregnancy

  • Review
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Autophagy exists widely in eukaryotic cells and is regulated by a variety of molecular mechanisms. Its physiological functions include providing energy, maintaining cell homeostasis, and promoting apoptosis of abnormal cells. At present, the regulation of autophagy in tumor, degenerative disease, and cardiovascular disease has attracted much attention. Gradually, the role of autophagy in pregnancy tends to be valued. The previous literature has shown that autophagy can influence the occurrence and maintenance of pregnancy from three aspects: embryo (affecting the process of fertilization and embryonic development and the function of trophoblast cells), maternal (decidualization), and maternal-to-fetal immune crosstalk. Undoubtedly, abnormalities in autophagy levels are associated with a variety of pregnancy complications, such as preeclampsia, fetal growth restriction, and preterm delivery which have been proven by human, animal, and in vitro experiments. The regulation of autophagy is expected to be a target for the treatment of these pregnancy complications. This article reviews the research on autophagy, especially about its physiological and pathological regulation during pregnancy.

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
Fig. 4

Similar content being viewed by others

References

  1. Shintani T (2004) Autophagy in health and disease: a double-edged sword [J]. Science 306(5698):990–995

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Kim YC, Guan KL (2015) mTOR: a pharmacologic target for autophagy regulation [J]. J Clin Investig 125(1):25–32

    PubMed  PubMed Central  Google Scholar 

  3. Kroemer G, Mariño G, Levine B (2010) Autophagy and the integrated stress response [J]. Mol Cell 40(2):280–293

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Fulda S, Kögel D (2015) Cell death by autophagy: emerging molecular mechanisms and implications for cancer therapy [J]. Oncogene 34(40):5105–5113

    CAS  PubMed  Google Scholar 

  5. Chen K, Cheng HH, Zhou RJ (2012) Molecular mechanisms and functions of autophagy and the ubiq-uitin-proteasome pathway [J]. Hereditas (Beijing) 34(1):5–18

    Google Scholar 

  6. Maryam M, Audrey E, Isabelle B et al (2010) Overview of macroautophagy regulation in mammalian cells [J]. Cell Res 20(7):748–762

    Google Scholar 

  7. Chen Y, Klionsky DJ (2011) The regulation of autophagy - unanswered questions. J Cell Sci 124:161–170

    CAS  PubMed  Google Scholar 

  8. Kim J, Klionsky DJ (2000) Autophagy, cytoplasm-to-vacuole targeting pathway, and pexophagy in yeast and mammalian cells [J]. Ann Rev Biochem 69(1):303–342

    CAS  PubMed  Google Scholar 

  9. Sun Q, Zhang J, Fan W et al (2011) The RUN domain of rubicon is important for hVps34 binding, lipid kinase inhibition, and autophagy suppression [J]. J Biol Chem 286(1):185–191

    CAS  PubMed  Google Scholar 

  10. Jaber N, Zong W-X (2013) Class III PI3K Vps34: essential roles in autophagy, endocytosis, and heart and liver function [J]. Ann New Acad Sci 1280:1

    Google Scholar 

  11. Clague MJ, Urbe S (2010) Ubiquitin:same molecule, different degration pathways [J]. Cell 143(5):682–685

    CAS  PubMed  Google Scholar 

  12. Tanida I (2011) Autophagosome formation and molecular mechanism of autophagy [J]. Antioxid Redox Signal 14(11):2201–2214

    CAS  PubMed  Google Scholar 

  13. Kebeya Y, Mizushima N, Ueno T et al (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing [J]. EMBO J 19(21):5720–5728

    Google Scholar 

  14. Suzuki NN, Yoshimoto K, Fujioka Y et al (2005) The crystal structure of plant ATG12 and its biological implication in autophagy [J]. Autophagy 1(2):119–126

    CAS  PubMed  Google Scholar 

  15. Longatti A, Tooze SA (2009) Vesicular trafficking and autophagosome formation [J]. Cell Death Differ 16(7):956–965

    CAS  PubMed  Google Scholar 

  16. Mizushima N, Yoshimori T, Ohsumi Y (2011) The role of Atg proteins in autophagosome formation [J]. Annu Rev Cell Dev Biol 27:107–132

    CAS  PubMed  Google Scholar 

  17. Tooze SA, Yoshimori T (2010) The origin of the autophagosomal membrane. Nat Cell Biol 12:831–835

    CAS  PubMed  Google Scholar 

  18. Rabanal-Ruiz Y, Otten E, Korolchuk-Viktor GI (2017) mTORC1 as the main gateway to autophagy [J]. Essay Bioch 61(6):565–584

    Google Scholar 

  19. Joungmok K, Mondira K, Benoit V et al (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1 [J]. Nature Cell Biol 13(2):132–141

    Google Scholar 

  20. Corradetti MN, Inoki K, Bardeesy N et al (2004) Regulation of the TSC pathway by LKB1:evidence of a molecular link between tuberous sclerosis complex and peutz -jeghers syndrome [J]. Genes Dev 18(13):1533–1538

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Li M, Jiang X, Liu D et al (2008) Autophagy protects LNCaP cells under androgen deprivation conditions [J]. Autophagy 4(1):54–60

    CAS  PubMed  Google Scholar 

  22. Gwinn DM, Shackelford DB, Egan DF et al (2008) AMPK phosphory-lation of raptor mediates a metabolic checkpoint [J]. Mol Cell 30(2):214–226

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Liang J, Shao SH, Xu ZX, Hennessy B, Ding Z et al (2007) The energy sensing LKB1-AMPK pathway regulates p27kip1 phosphorylation mediating the decision to enter autophagy or apoptosis. Nat Cell Biol 9:218–224

    CAS  PubMed  Google Scholar 

  24. Bunney TD, Katan M (2010) Phosphoinositide signaling in cancer:beyond PI3K and PTEN [J]. Nat Rev Cancer 10(5):342–352

    CAS  PubMed  Google Scholar 

  25. Latres E, Amini AR, Amini AA et al (2005) Insulin-like growth factor-1 (IGF -1)inversely regulates atrophy-induced genes via the phosphatidylinositol3-kinse/ Akt/mammalian target of rapamycin(PI3K/Akt/mTOR)pathway [J]. J Biol Chem 280(4):2737–2744

    CAS  PubMed  Google Scholar 

  26. Shen-Jeu W, Cheng-Hsin Y, Hsiao-Sheng L et al (2015) Justicidin a-induced autophagy flux enhances apoptosis of human colorectal cancer cells via class III PI3K and Atg5 pathway [J]. J Cell Physiol 230(4):930–946

    Google Scholar 

  27. Lum JJ, Bauer DE, Kong M et al (2005) Growth factor regulation of autophagy and cell survival in the absence of apoptosis [J]. Cell 120:237–248

    CAS  PubMed  Google Scholar 

  28. Long X, Ortiz-Vega S, Lin Y, Avruch J (2005) Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency [J]. J Biol Chem 280:23433–23436

    CAS  PubMed  Google Scholar 

  29. Jager S, Bucci C, Tanida I et al (2004) Role for Rab7 in maturation of late autophagic vacuoles [J]. J Cell Sci 117:4837–4848

    PubMed  Google Scholar 

  30. Daniela KB, Stephano SM, Kathryn TB et al (2013) Global genomic profiling reveals an extensive p53-regulated autophagy program contributing to key p53 responses [J]. Genes Devel 27(9):1016–1031

    Google Scholar 

  31. Nadja B, Thomas GH (2009) Apoptosis and autophagy: regulation of apoptosis by DNA damage signaling roles of p53, p73 and HIPK2 [J]. Febs J 276(21):6074–6083

    Google Scholar 

  32. Ghavami S, Mutawe MM, Sharma P et al (2011) Mevalonate cascade regulation of airway mesenchymal cell autophagy and apoptosis:a dual role for P53 [J]. PLoS ONE 6(1):e16523

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Tasdemir E, Maiuri MC, Galluzzi L et al (2008) Regulation of autophage by cytoplasmic p53 [J]. Nat Cell Biol 10(6):676–687

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Kenzelmann Broz D, Spano Mello S, Bieging KT et al (2013) Global genomic profiling reveals an extensive p53-regulated autophagy program contributing to key p53 responses [J]. Genes Dev 27:1016–1031

    PubMed  PubMed Central  Google Scholar 

  35. Ali A, Shah AS, Ahmad A (2008) Gain-of-function of mutant p53: mutant p53 enhances cancer progression by inhibiting KLF17 expression in invasive breast carcinoma cells [J]. Cancer Lett 354(1):87–96

    Google Scholar 

  36. Sato M, Sato K (2013) Dynamic regulation of autophagy and endocytosis for cell remodeling during early development [J]. Traffic 14:479–486

    CAS  PubMed  Google Scholar 

  37. Choi AM, Ryter SW, Levine B (2013) Autophagy in human health and disease [J]. N Engl J Med 368:1845–1846

    CAS  PubMed  Google Scholar 

  38. Tsukamoto S, Kuma A, Murakami M et al (2008) Autophagy is essential for preimplantation development of mouse embryos [J]. Science 321(5885):11–72

    Google Scholar 

  39. He C, Levine B (2010) The beclin 1 interactome [J]. Curr Opin Cell Biol 22(2):19–49

    Google Scholar 

  40. Yue Z, Jin S, Yang C et al (2003) Beclin 1, an autophagy gene essential for early embryonic development, is a haplo insufficient tumor suppressor [J]. Proc Natl Acad Sci USA 100(25):150–782

    Google Scholar 

  41. Gan B, Peng X, Nagy T, Alcaraz A, Gu H, Guan JL (2006) Role of FIP200 in cardiac and liver development and its regulation of TNF-alpha and TSC-mTOR signaling pathways [J]. J Cell Biol 175(1):12–33

    Google Scholar 

  42. Fimia GM, Stoykova A, Romagnoli A, Giunta L, Di Bartolomeo S, Nardacci R et al (2007) Ambra1 regulates autophagy and development of the nervous system [J]. Nature 447(7148):11–25

    Google Scholar 

  43. Lee JE, Oh HA, Song H, Jun JH, Roh CR, Xie H, Dey SK, Lim HJ (2011) Autophagy regulates embryonic survival during delayed implantation [J]. Endocrinology 152:2067–2075

    CAS  PubMed  Google Scholar 

  44. Cornelia M-S, Alexandra F, Nina-Naomi K (2007) Function of survivin in trophoblastic cells of the placenta [J]. Placenta 34(9):27

    Google Scholar 

  45. Gude NM, Roberts CT, Kalionis B et al (2008) Growth and function of the normal human placenta [J]. Throm Res 114(56):407

    Google Scholar 

  46. Rama S, Rao AJ (2003) Regulation of growth and function of the human placenta [J]. Mol Cell Biochem 253(1–2):263–268

    CAS  PubMed  Google Scholar 

  47. Pringle KG, Kind KL, Sferruzzi-Perri AN, Thompson JG, Roberts CT (2010) Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy [J]. Hum Reprod Update 16(4):41–531

    Google Scholar 

  48. Genbacev O, Zhou Y, Ludlow JW, Fisher SJ (1997) Regulation of human placental development by oxygen tension [J]. Science 277(5332):166–972

    Google Scholar 

  49. Nishida K, Yamaguchi O, Otsu K (2008) Crosstalk between autophagy and apoptosis in heart disease. Circ Res 103:343–351

    CAS  PubMed  Google Scholar 

  50. Tsukamoto S, Kuma A, Murakami M et al (2008) Mizushima: Autophagy is essential for preimplantation development of mouse embryos [J]. Science 321:117–120

    CAS  PubMed  Google Scholar 

  51. Chifenti B, Locci MT, Lazzeri G et al (2013) Autophagy -related protein LC3 and beclin-1 in the first trimester of pregnancy [J]. Clin Exp Reprod Med 40(1):33–37

    PubMed  PubMed Central  Google Scholar 

  52. Hung TH, Tsang-Tang H, Chen SF et al (2013) Autophagy in the human placenta throughout gestation [J]. PLoS ONE 8:1–12

    Google Scholar 

  53. Nakashima A, Yamanaka-Tatematsu M, Fujita N et al (2013) Impaired autophagy by soluble endoglin, under physiological hypoxia in early pregnant period, is involved in poor placentation in preeclampsia [J]. Autophagy 9:303–316

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Bilban M, Tauber S, Haslinger P, Pollheimer J, Saleh L, Pehamberger H et al (2010) Trophoblast invasion: assessment of cellular models using gene expression signatures [J]. Placenta 31(11):98–996

    Google Scholar 

  55. Jauniaux E, Watson A, Burton G (2001) Evaluation of respiratory gases and acid-base gradients in human fetal fluids and uteroplacental tissue between 7 and 16 weeks’ gestation [J]. Am J Obstet Gynecol 184(5):998–1003

    CAS  PubMed  Google Scholar 

  56. Kajihara T, Tanaka K, Oguro T et al (2014) Androgens modulate the morphological characteristics of human endometrial stromal cells decidualized in vitro [J]. Reprod Sci 21(3):372–380

    PubMed  Google Scholar 

  57. Lane B, Oxberry W, Mazella J (1994) Decidualization of human endometrial stromal cells in vitro: effects of progestin and relaxin on the ultrastructure and production of decidual secretory proteins [J]. Hum Reprod 9:259–266

    CAS  PubMed  Google Scholar 

  58. Ramathal C, Bagchi I, Taylor R et al (2010) Endometrial decidualization: of mice and men [J]. Sem Reprod Med 28(01):017–026

    CAS  Google Scholar 

  59. Dey SK, Lim H, Das SK et al (2004) Molecular cues to implantation [J]. Endocr Rev 25:341–373

    CAS  PubMed  Google Scholar 

  60. Large MJ, DeMayo FJ (2012) The regulation of embryo implantation and endometrial decidualization by progesterone receptor signaling [J]. Mol Cell Endocrinol 358:155–165

    CAS  PubMed  Google Scholar 

  61. Meng N, Yang Q, He Y et al (2019) Decreased NDRG1 expression is associated with pregnancy loss in mice and attenuates the in vitro decidualization of endometrial stromal cells [J]. Mole Reprod Dev 2:1–4

    Google Scholar 

  62. Choi J, Jo M, Lee E, Oh YK, Choi D (2012) The role of autophagy in human endometrium [J]. Biol Reprod 86:1–10

    Google Scholar 

  63. Mestre Citrinovitz AC, Strowitzki T, Germeyer A (2019) Decreased autophagy impairs decidualization of human endometrial stromal cells: a role for atg proteins in endometrial physiology [J]. Int J Mol Sci 20(12):3066

    PubMed Central  Google Scholar 

  64. Avagliano L, Terraneo L, Virgili E et al (2015) Autophagy in normal and abnormal early human pregnancies [J]. Reprod Sci 22(7):838–844

    PubMed  Google Scholar 

  65. Rhee JS, Saben JL, Mayer AL et al (2016) Diet-induced obesity impairs endometrial stromal cell decidualization: a potential role for impaired autophagy [J]. Hum Reprod 2:48

    Google Scholar 

  66. Chen Q, Gao R, Geng Y et al (2018) Decreased autophagy was implicated in the decreased apoptosis during decidualization in early pregnant mice [J]. J Mol Histol 49(6):589–597

    CAS  PubMed  Google Scholar 

  67. Najafi S, Hadinedoushan H, Eslami G et al (2014) Association of IL-17A and IL-17 F gene polymorphisms with recurrent pregnancy loss in Iranian women [J]. J Assist Reprod Genet 31:1491–1496

    PubMed  PubMed Central  Google Scholar 

  68. Guerin LR, Prins JR, Robertson SA (2005) Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? [J]. Hum Reprod Update 15(5):517–535

    Google Scholar 

  69. Ana SF, Anne S (2016) The Th17/Treg paradigm in pregnancy [J]. Immunology 148(1):13–21

    Google Scholar 

  70. Zenclussen AC, Hammerling GJ (2014) Cellular regulation of the uterine microenvironment that enables embryo implantation [J]. Placenta 35:241–248

    Google Scholar 

  71. Yuan J, Li J, Huang SY (2015) Characterization of the subsets of human NKT-like cells and the expression of Th1/Th2 cytokines in patients with unexplained recurrent spontaneous abortion [J]. J Reprod Immunol 110:81–88. https://doi.org/10.1016/j.jri.2015.05.001 (Epub 2015 May 27)

    Article  CAS  PubMed  Google Scholar 

  72. Jasper MJ, Tremellen KP, Robertson SA (2006) Primary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue [J]. Mol Hum Reprod 12:301–308

    CAS  PubMed  Google Scholar 

  73. Ma Y, Galluzzi L, Zitvogel L et al (2008) Autophagy and cellular immune responses [J]. Immunity 39(2):211–227

    Google Scholar 

  74. Younho C, James WB, Jae UJ (2018) Autophagy during viral infection - a double-edged sword [J]. Nature Rev Microbiol 16(6):341–354

    Google Scholar 

  75. Lu JV, Walsh CM (1998) Programmed necrosis and autophagy in immune function [J]. Immunol Rev 249(1):205–217

    Google Scholar 

  76. Jia W, Pua HH, Li QJ et al (2011) Autophagy regulates endoplasmic reticulum homeostasis and calcium mobilization in T lymphocytes [J]. J Immunol 186(3):1564–1574

    CAS  PubMed  Google Scholar 

  77. Djavaheri-Mergny M, Amelotti M, Mathieu J et al (2006) NF-kappaB activation represses tumor necrosis factor-alpha-induced autophagy [J]. J Biol Chem 281:30373–30382

    CAS  PubMed  Google Scholar 

  78. Dengjel J, Schoor O, Fischer R, Reich M, Kraus M, Muller M et al (2005) Autophagy promotes MHC class II presentation of peptides from intracellular source proteins [J]. Proc Natl Acad Sci USA 102:7922–7927

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Deretic V (2009) Multiple regulatory and effector roles of autophagy in immunity. Curr Opin Immunol 21:53–62

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Basu S, Golovina T, Mikheeva T, June CH, Riley JL (2008) Cutting edge: Foxp3-mediated induction of Pim 2 allows human T regulatory cells to preferentially expand in rapamycin [J]. J Immunol 180:5794–5798

    CAS  PubMed  Google Scholar 

  81. Yue Z, Jin S, Yang C, Levine AJ, Heintz N (2003) Beckin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor [J]. Proc Natl Acad Sci USA 100:15077–15082

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Kanninen TT, Ramos BR, Jaffe S, Bongiovanni AM, Linhares IM, Di Renzo GC, Witkin SS (2013) Inhibition of autophagy by sera from pregnant women [J]. Reprod Sci 20:1327–1331

    CAS  PubMed  Google Scholar 

  83. Say L, Chou D, Gemmill A, Tuncalp O, Moller AB, Daniels J, Gulmezoglu AM, Temmerman M, Alkema L (2014) Global causes of maternal death: a WHO systematic analysis [J]. Lancet Glob Health 2:323–333

    Google Scholar 

  84. American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy (2013) Hypertension in pregnancy. Report of the American college of obstetricians and gynecologists’ task force on hypertension in pregnancy [J]. Obstet Gynecol 122(5):1122–1131

  85. Sibai BM (2003) Diagnosis and management of gestational hypertension and preeclampsia [J]. Obstet Gynecol 102:181–192

    PubMed  Google Scholar 

  86. Kalkunte S, Boij R, Norris W et al (2010) Sera from preeclampsia patients elicit symptoms of human disease in mice and provide a basis for an in vitro predictive assay [J]. Am J Pathol 177(5):23–98

    Google Scholar 

  87. Nakabayashi Y, Nakashima A, Yoshino O et al (2016) Impairment of the accumulation of decidual T cells, NK cells, and monocytes, and the poor vascular remodeling of spiral arteries, were observed in oocyte donation cases, regardless of the presence or absence of preeclampsia [J]. Autophagy 114:65–74

    CAS  Google Scholar 

  88. Akitoshi N, Shi-Bin C, Masahito I et al (2019) Evidence for lysosomal biogenesis proteome defect and impaired autophagy in preeclampsia [J]. Autophagy 12:1–15

    Google Scholar 

  89. Akaishi R, Yamada T, Nakabayashi K et al (2014) Autophagy in the placenta of women with hypertensive disorders in pregnancy [J]. Placenta 35(12):974–980

    CAS  PubMed  Google Scholar 

  90. Melland-Smith M, Ermini L, Chauvin S et al (2015) Disruption of sphingolipid metabolism augments ceramide-induced autophagy in preeclampsia [J]. Autophagy 11(4):653–669

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Nakashima A, Yamanaka-Tatematsu M, Fujita N et al (2013) Impaired autophagy by soluble endoglin under physiological hypoxia in early pregnant period, is involved in poor placentation in preeclampsia [J]. Autophagy 9(3):303–316

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Churchill D, Bayliss H, Beevers G (2000) Fetal growth restriction [J]. The Lancet 355(9212):1366–1367

    CAS  Google Scholar 

  93. McCance DR, Pettitt DJ, Hanson RL et al (1994) Birth weight and non-insulin dependent diabetes: thrifty genotype, thrifty phenotype, or surviving small baby genotype? [J]. BMJ 308:942–945

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Creasy RK, Resnik R (1994) Maternal-fetal medicine: principles and practice [M]. J Nat Commun 16:1–34

    Google Scholar 

  95. Miura S, Sato K, Kato-Negishi M, Teshima T, Takeuchi S (2015) Fluid shear triggers microvilli formation via mechanosensitive activation of TRPV6 [J]. Nat Commun 6:8871

    PubMed  Google Scholar 

  96. Clark AR, Lin M, Tawhai M, Saghian R, James JL (2015) Multiscale modelling of the feto-placental vasculature [J]. Int Focus 5(2):20140078

    CAS  Google Scholar 

  97. Liu J, Bi X, Chen T et al (2015) Shear stress regulates endothelial cell autophagy via redox regulation and Sirt1 expression [J]. Cell Death Dis 6:e1827

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Kojima T, Yamada T, Akaishi R et al (2015) Role of the Atg9a gene in intrauterine growth and survival of fetal mice [J]. Reprod Biol 15:131–138

    PubMed  Google Scholar 

  99. Zhang QX, Na Q, Song W (2017) Altered expression of mTOR and autophagy in term normal human placentas [J]. J Embryol 58(2):517–526

    Google Scholar 

  100. Mihu CM, Şuşman S, Rus Ciucă D, Mihu D, Costin N (2009) Aspects of placental morphogenesis and angiogenesis [J]. Rom J Morphol Embryol 50(4):549–557

    PubMed  Google Scholar 

  101. Yung HW, Calabrese S, Hynx D et al (2008) Evidence of placental translation inhibition and endoplasmic reticulum stress in the etiology of human intrauterine growth restriction [J]. Am J Pathol 173(2):451–462

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Veerbeek JH, Tissot Patot MC, Burton GJ, Yung HW (2015) Endoplasmic reticulum stress is induced in the human placenta during labour [J]. Placenta 36(1):88–92

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Jansson T, Aye ILMH, Goberdhan DCI (2012) The emerging role of mTORC1 signaling in placental nutrient-sensing [J]. Placenta 33:e23–e29

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Chen Y, Klionsky DJ (2011) The regulation of autophagy–unanswered questions [J]. J Cell Sci 124:161–170

    CAS  PubMed  Google Scholar 

  105. Smith SC, Baker PN, Symonds EM (1997) Increased placental apoptosis in intrauterine growth restriction [J]. Am J Obstet Gynecol 177:1395–1401

    CAS  PubMed  Google Scholar 

  106. Romero R, Dey SK, Fisher SJ (2014) Preterm labor: one syndrome, many causes [J]. Science 345:760–765

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Gawriluk TR, Rucker EB (2015) BECN1, corpus luteum function, and preterm labor [J]. Autophagy 11:183–184

    PubMed  PubMed Central  Google Scholar 

  108. Cha J, Bartos A, Egashira M et al (2013) Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions [J]. J Clin Invest 123:4063–4075

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Hirota Y, Cha J, Yoshie M et al (2011) Heightened uterine mammalian target of rapamycin complex 1 (mTIORC1) signaling provokes preterm birth in mice [J]. Proc Natl Acad Sci USA 108:18073–18078

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Agrawal V, Jaiswal MK, Mallers T et al (2015) Altered autophagic flux enhances inflammatory responses during inflammation-induced preterm labor [J]. Sci Rep 5:9410

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Doulaveris G, Orfanelli S, Benn K et al (2013) A polymorphism in an autophagy-related gene, ATG16L1, influences time to delivery in women with an unfavorable cervix who require labor induction [J]. J Perinat Med 41:411–414

    CAS  PubMed  Google Scholar 

  112. Kabat AM, Harrison OJ, Riffelmacher T et al ( 2016) The autophagy gene ATG16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation [J]. eLife 5:12–444

    Google Scholar 

  113. Cao B, Macones C, Mysorekar IU (2016) ATG16L1 governs placental infection risk and preterm birth in mice and women [J]. JCI Insight 1:e86654

    PubMed  PubMed Central  Google Scholar 

  114. Doulaveris G, Orfanelli S, Benn K et al (2013) A polymorphism in an autophagy- related gene, ATG16L1, influences time to delivery in women with an unfavorable cervix who require labor induction [J]. J Perinat Med 41:411–414

    CAS  PubMed  Google Scholar 

  115. Saitoh T, Akira S (2016) Regulation of inflammasomes by autophagy [J]. J Allergy Clin Immunol 138:28–36

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Special thanks are also extended to colleagues at the First Affiliated Hospital of Heilongjiang University of Chinese Medicine and Zhejiang Chinese Medical University.

Funding

This research was funded by the National Natural Fund Project (Grant No. 81973894) the Project of General Undergraduate University Youth Innovation Talents by Education Department of Heilongjiang Province (Grant No. UNPYSCT-2018227), and Ph.D. innovation fund (Grant No. 2018bs07).

Author information

Authors and Affiliations

Authors

Contributions

XZ, YJ, TJ, and XH wrote the manuscript. YW, LC, and FX took charge of the examination and modification of articles. XZ, YW, and LC revised the manuscript.

Corresponding author

Correspondence to Xiaoling Feng.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there are no conflicts of interest.

Ethical approval

No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication.

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

Zhao, X., Jiang, Y., Jiang, T. et al. Physiological and pathological regulation of autophagy in pregnancy. Arch Gynecol Obstet 302, 293–303 (2020). https://doi.org/10.1007/s00404-020-05607-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-020-05607-1

Keywords

Navigation