Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-22T21:54:28.400Z Has data issue: false hasContentIssue false
  • English
  • Français

Preeclampsia link to gestational hypoxia

Part of: DOHaD 2017 World Congress

Published online by Cambridge University Press:  10 April 2019

W. Tong  and
D. A. Giussani Open the ORCID record for D. A. Giussani [Opens in a new window]
W. Tong
Affiliation:
Department of Physiology Development & Neuroscience, University of Cambridge, Cambridge, UK Centre for Trophoblast Research, University of Cambridge, Cambridge, UK Cardiovascular Strategic Research Initiative, University of Cambridge, Cambridge, UK Cambridge Reproductive Strategic Research Initiative, University of Cambridge, Cambridge, UK
D. A. Giussani*
Affiliation:
Department of Physiology Development & Neuroscience, University of Cambridge, Cambridge, UK Centre for Trophoblast Research, University of Cambridge, Cambridge, UK Cardiovascular Strategic Research Initiative, University of Cambridge, Cambridge, UK Cambridge Reproductive Strategic Research Initiative, University of Cambridge, Cambridge, UK
*
Author for correspondence: E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Complications of pregnancy remain key drivers of morbidity and mortality, affecting the health of both the mother and her offspring in the short and long term. There is lack of detailed understanding of the pathways involved in the pathology and pathogenesis of compromised pregnancy, as well as a shortfall of effective prognostic, diagnostic and treatment options. In many complications of pregnancy, such as in preeclampsia, there is an increase in uteroplacental vascular resistance. However, the cause and effect relationship between placental dysfunction and adverse outcomes in the mother and her offspring remains uncertain. In this review, we aim to highlight the value of gestational hypoxia-induced complications of pregnancy in elucidating underlying molecular pathways and in assessing candidate therapeutic options for these complex disorders. Chronic maternal hypoxia not only mimics the placental pathology associated with obstetric syndromes like gestational hypertension at morphological, molecular and functional levels, but also recapitulates key symptoms that occur as maternal and fetal clinical manifestations of these pregnancy disorders. We propose that gestational hypoxia provides a useful model to study the inter-relationship between placental dysfunction and adverse outcomes in the mother and her offspring in a wide array of examples of complicated pregnancy, such as in preeclampsia.

Keywords

compromised pregnancyfetal growth restrictiongestational hypoxiaoxidative stressplacental dysfunction
Type
Review
Information
Journal of Developmental Origins of Health and Disease , Volume 10 , Issue 3 , June 2019 , pp. 322 - 333
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Alkema, L, Chou, D, Hogan, D, et al. Global, regional, and national levels and trends in maternal mortality between 1990 and 2015, with scenario-based projections to 2030: a systematic analysis by the UN Maternal Mortality Estimation Inter-Agency Group. The Lancet. 2016; 387, 462–474.CrossRefGoogle ScholarPubMed
2. Zupan J, Ahman E. Neonatal and Perinatal Mortality: Country, Regional and Global Estimates. World Health Organization. 2007; Department of Making Pregnancy Safer.Google Scholar
3. Bernstein, IM, Horbar, JD, Badger, GJ, Ohlsson, A, Golan, A. Morbidity and mortality among very-low-birth-weight neonates with intrauterine growth restriction. Am J Obstet Gynecol. 2000; 182, 198–206.CrossRefGoogle ScholarPubMed
4. Gillman, MW. Mothers, babies, and disease in later life. BMJ. 1995; 310, 68–69.CrossRefGoogle Scholar
5. Gluckman, PD, Hanson, MA, Cooper, C, Thornburg, KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008; 359, 61–73.CrossRefGoogle ScholarPubMed
6. Eiríksdóttir, VH, Ásgeirsdóttir, TL, Bjarnadóttir, RI, et al. Low birth weight, small for gestational age and preterm births before and after the economic collapse in iceland: a population based cohort study. PLoS One 2013; 8, e80499.CrossRefGoogle ScholarPubMed
7. Usynina, AA, Grjibovski, AM, Odland, JØ, Krettek, A. Social correlates of term small for gestational age babies in a Russian Arctic setting. Int J Circumpolar Health. 2016; 75, 32883–32883.CrossRefGoogle Scholar
8. Liu, S, Basso, O, Kramer, MS. Association between unintentional injury during pregnancy and excess risk of preterm birth and its neonatal sequelae. Am J Epidemiol. 2015; 182, 750–758.CrossRefGoogle ScholarPubMed
9. Say, L, Chou, D, Gemmill, A, et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014; 2, e323–e333.CrossRefGoogle ScholarPubMed
10. Hodgins, S. Pre-eclampsia as underlying cause for perinatal deaths: time for action. Glob Health: Sci Pract. 2015; 3, 525–527.Google Scholar
11. Ngan Kee, WD. Confidential enquiries into maternal deaths: 50 years of closing the loop. Br J Anaesth. 2005; 94, 413–416.CrossRefGoogle Scholar
12. Meschia, G. Circulation to female reproductive organs. Compr Physiol 2011; Supplement 8: Handbook of Physiology, The Cardiovascular System, Peripheral Circulation and Organ Blood Flow (First published in print 1983), 241–269.CrossRefGoogle Scholar
13. Trudinger, BJ, Giles, WB, Cook, CM. Uteroplacental blood flow velocity‐time waveforms in normal and complicated pregnancy. BJOG: An Int J Obstet Gynaecol. 1985; 92, 39–45.CrossRefGoogle ScholarPubMed
14. Ferrell, CL. Placental regulation of fetal growth. In Animal Growth Regulation (eds. Campion DR, Hausman GJ, Martin RJ), 1989; pp. 1–19. Springer: Boston, MA.Google Scholar
15. Poston, L. The control of blood flow to the placenta. Exp Physiol. 1997; 82, 377–387.CrossRefGoogle ScholarPubMed
16. Lang, U, Baker, RS, Braems, G, et al. Uterine blood flow—a determinant of fetal growth. Eur J Obstet Gynecol Reprod Biol. 2003; 110(Suppl 1), S55–61.CrossRefGoogle ScholarPubMed
17. Gaillard, R, Steegers, EAP, Tiemeier, H, Hofman, A, Jaddoe, VWV. Placental vascular dysfunction, fetal and childhood growth, and cardiovascular development. The Generation R Study. 2013; 128, 2202–2210.Google ScholarPubMed
18. Hennington, BS, Alexander, BT. Linking IUGR and blood pressure: insight into the human origins of cardiovascular disease. Circulation. 2013; 128, 2179–2180.CrossRefGoogle Scholar
19. Godfrey, KM. The role of the placenta in fetal programming—a review. Placenta. 2002; 23, S20–S27.CrossRefGoogle ScholarPubMed
20. Reynolds, LP, Caton, JS, Redmer, DA, et al. Evidence for altered placental blood flow and vascularity in compromised pregnancies. J Physiol. 2006; 572(Pt 1), 51–58.CrossRefGoogle ScholarPubMed
21. Swanson, AM, David, AL. Animal models of fetal growth restriction: considerations for translational medicine. Placenta. 2015; 36, 623–630.CrossRefGoogle ScholarPubMed
22. Furukawa, S, Kuroda, Y, Sugiyama, A. A comparison of the histological structure of the placenta in experimental animals. J Toxicol Pathol. 2014; 27, 11–18.CrossRefGoogle ScholarPubMed
23. Bibeau, K, Sicotte, B, Beland, M, et al. Placental underperfusion in a rat model of intrauterine growth restriction induced by a reduced plasma volume expansion. PLoS One. 2016; 11, e0145982.CrossRefGoogle Scholar
24. Intapad, S, Warrington, JP, Spradley, FT, et al. Reduced uterine perfusion pressure induces hypertension in the pregnant mouse. Am J Physiol Regul Integr Comp Physiol. 2014; 307, R1353–1357.CrossRefGoogle ScholarPubMed
25. Kulandavelu, S, Whiteley, KJ, Bainbridge, SA, Qu, D, Adamson, SL. Endothelial NO synthase augments fetoplacental blood flow, placental vascularization, and fetal growth in mice. Hypertension. 2013; 61, 259–266.CrossRefGoogle ScholarPubMed
26. VanWijk, MJ, Kublickiene, K, Boer, K, VanBavel, E. Vascular function in preeclampsia. Cardiovasc Res. 2000; 47, 38–48.CrossRefGoogle ScholarPubMed
27. Zamudio, S, Wu, Y, Ietta, F, et al. Human placental hypoxia-inducible factor-1alpha expression correlates with clinical outcomes in chronic hypoxia in vivo. Am J Pathol. 2007; 170, 2171–2179.CrossRefGoogle ScholarPubMed
28. Schoots, MH, Gordijn, SJ, Scherjon, SA, van Goor, H, Hillebrands, JL. Oxidative stress in placental pathology. Placenta. 2018; 69, 153-161.Google Scholar
29. Burton, GJ, Jauniaux, E. Placental oxidative stress: from miscarriage to preeclampsia. J Soc Gynecol Investig. 2004; 11, 342–352.CrossRefGoogle ScholarPubMed
30. Tissot van Patot, MC, Ebensperger, G, Gassmann, M, Llanos, AJL. The hypoxic placenta. High Alt Med Biol. 2012; 13, 176–184.CrossRefGoogle Scholar
31. Gilbert, JS, Ryan, MJ, LaMarca, BB, et al. Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2008; 294, H541–H550.CrossRefGoogle ScholarPubMed
32. Woods, LL. Importance of prostaglandins in hypertension during reduced uteroplacental perfusion pressure. Am J Physiol-Regul Integr Comp Physiol. 1989; 257, R1558–R1561.CrossRefGoogle ScholarPubMed
33. Brown, MA, Wang, J, Whitworth, JA. The renin–angiotensin–aldosterone system in pre-eclampsia. Clin Exp Hypertens. 1997; 19(5-6), 713–726.CrossRefGoogle ScholarPubMed
34. Gillis, EE, Williams, JM, Garrett, MR, Mooney, JN, Sasser, JM. The Dahl salt-sensitive rat is a spontaneous model of superimposed preeclampsia. Am J Physiol-Regul Integr Comp Physiol. 2015; 309, R62–R70.CrossRefGoogle ScholarPubMed
35. Mata-Greenwood, E, Blood, AB, Sands, LD, et al. A novel rodent model of pregnancy complications associated with genetically determined angiotensin converting enzyme (ACE) activity. Am J Physiol-Endocrinol Metab. 2018; 315, E52–E62.CrossRefGoogle ScholarPubMed
36. Samuel, J, Franklin, C. Hypoxemia and hypoxia. In Common Surgical Diseases: An Algorithmic Approach to Problem Solving (eds. Myers JA, Millikan KW, Saclarides TJ), 2008; pp. 391–394. Springer: New York, NY.CrossRefGoogle Scholar
37. Matsuda, Y, Patrick, J, Carmichael, L, Fraher, L, Richardson, B. American Journal of Obstetrics and Gynecology, 1994; 170, 1433–1441.CrossRefGoogle Scholar
38. Xiao, D, Hu, X-Q, Huang, X, et al. Chronic hypoxia during gestation enhances uterine arterial myogenic tone via heightened oxidative stress. PLoS One. 2013; 8, e73731.CrossRefGoogle ScholarPubMed
39. Vargas, VE, Kaushal, KM, Monau, T, Myers, DA, Ducsay, CA. Long-term hypoxia enhances cortisol biosynthesis in near-term ovine fetal adrenal cortical cells. Reproductive Sciences. 2011; Vol. 18, pp. 277–285. Thousand Oaks: CA, USA.Google Scholar
40. Myers, DA, Singleton, K, Hyatt, K, et al. Long-term gestational hypoxia modulates expression of key genes governing mitochondrial function in the perirenal adipose of the late gestation sheep fetus. Reproductive Sciences. 2015; Vol. 22, pp. 654–663. Thousand Oaks: CA, USA.Google Scholar
41. Aljunaidy, MM, Morton, JS, Cooke, CL, Davidge, ST. Maternal vascular responses to hypoxia in a rat model of intrauterine growth restriction. Am J Physiol Regul Integr Comp Physiol. 2016; 311, R1068–R1075.CrossRefGoogle Scholar
42. Turan, S, Aberdeen, GW, Thompson, LP. Chronic hypoxia alters maternal uterine and fetal hemodynamics in the full-term pregnant guinea pig. Am J Physiol-Regul Integr Comp Physiol. 2017; 313, R330–R339.CrossRefGoogle ScholarPubMed
43. Chang, K, Xiao, D, Huang, X, Longo, LD, Zhang, L. Chronic hypoxia increases pressure-dependent myogenic tone of the uterine artery in pregnant sheep: role of ERK/PKC pathway. Am J Physiol-Heart Circ Physiol. 2009; 296, H1840–H1849.CrossRefGoogle ScholarPubMed
44. Rockwell, LC, Dempsey, EC, Moore, LG. Chronic hypoxia diminishes the proliferative response of Guinea pig uterine artery vascular smooth muscle cells in vitro. High Alt Med Biol. 2006; 7, 237–244.CrossRefGoogle ScholarPubMed
45. Rockwell, LC, Keyes, LE, Moore, LG. Chronic hypoxia diminishes pregnancy-associated DNA synthesis in guinea pig uteroplacental arteries. Placenta. 2000; 21, 313–319.CrossRefGoogle ScholarPubMed
46. Mateev, S, Sillau, AH, Mouser, R, et al. Chronic hypoxia opposes pregnancy-induced increase in uterine artery vasodilator response to flow. Am J Physiol-Heart Circ Physiol. 2003; 284, H820–H829.CrossRefGoogle Scholar
47. Matheson, H, Veerbeek, JH W, Charnock‐Jones, D S, Burton, GJ, Yung, HW. Morphological and molecular changes in the murine placenta exposed to normobaric hypoxia throughout pregnancy. J Physiol. 2016; 594, 1371–1388.CrossRefGoogle ScholarPubMed
48. Zhou, J, Xiao, D, Hu, Y, et al. Gestational hypoxia induces preeclampsia-like symptoms via heightened endothelin-1 signaling in pregnant rats. Hypertension. 2013; 62, 599–607.CrossRefGoogle ScholarPubMed
49. Herrera, EA, Krause, B, Ebensperger, G, et al. The placental pursuit for an adequate oxidant balance between the mother and the fetus. Front Pharmacol. 2014; 5, 149.CrossRefGoogle Scholar
50. Tomlinson, TM, Garbow, JR, Anderson, JR, et al. Magnetic resonance imaging of hypoxic injury to the murine placenta. Am J Physiol-Regul Integr Comp Physiol. 2010; 298, R312–R319.CrossRefGoogle ScholarPubMed
51. Thaete, LG, Dewey, ER, Neerhof, MG. Endothelin and the Regulation of Uterine and Placental Perfusion in Hypoxia-Induced Fetal Growth Restriction. J Soc Gynecol Investig. 2004; 11, 16–21.CrossRefGoogle ScholarPubMed
52. Moore, LG, Hershey, DW, Jahnigen, D, Bowes, W. The incidence of pregnancy-induced hypertension is increased among Colorado residents at high altitude. Am J Obstet Gynecol. 1982; 144, 423–429.CrossRefGoogle ScholarPubMed
53. Reshetnikova, OS, Burton, GJ, Milovanov, AP, Fokin, EI. Increased incidence of placental chorioangioma in high-altitude pregnancies: hypobaric hypoxia as a possible etiologic factor. Am J Obstet Gynecol. 1996; 174, 557–561.CrossRefGoogle ScholarPubMed
54. Kimball, R, Wayment, M, Merrill, D, et al. Hypoxia reduces placental mTOR activation in a hypoxia-induced model of intrauterine growth restriction (IUGR). Physiol Rep. 2015; 3, e12651.CrossRefGoogle Scholar
55. Jang, EA, Longo, LD, Goyal, R. Antenatal maternal hypoxia: criterion for fetal growth restriction in rodents. Frontiers Physiol. 2015; 6, 176.CrossRefGoogle ScholarPubMed
56. Giussani, DA. Hypoxia, fetal growth and developmental origins of health and disease. In Early Life Origins of Health and Disease (eds. Wintour EM, Owens JA), 2006; pp. 219–224. Springer: Boston, MA.CrossRefGoogle Scholar
57. Giussani, DA, Davidge, ST. Developmental programming of cardiovascular disease by prenatal hypoxia. J Dev Orig Health Dis. 2013; 4, 328–337.CrossRefGoogle ScholarPubMed
58. Perrone, S, Tataranno, ML, Negro, S, et al. Placental histological examination and the relationship with oxidative stress in preterm infants. Placenta. 2016; 46, 72–78.CrossRefGoogle ScholarPubMed
59. Longini, M, Perrone, S, Vezzosi, P, et al. Association between oxidative stress in pregnancy and preterm premature rupture of membranes. Clin Biochem. 2007; 40, 793–797.CrossRefGoogle ScholarPubMed
60. Yung, HW, Cox, M, Tissot van Patot, M, Burton, GJ. Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude. FASEB J. 2012; 26, 1970–1981.CrossRefGoogle ScholarPubMed
61. Genbacev, O, Joslin, R, Damsky, CH, Polliotti, BM, Fisher, SJ. Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia. J Clin Investig. 1996; 97, 540–550.CrossRefGoogle ScholarPubMed
62. Thompson, LP, Pence, L, Pinkas, G, Song, H, Telugu, BP. Placental hypoxia during early pregnancy causes maternal hypertension and placental insufficiency in the hypoxic Guinea pig model. Biol Reprod. 2016; 128, 1–10.Google Scholar
63. Keyes, LE, Armaza, JF, Niermeyer, S, et al. Intrauterine growth restriction, preeclampsia, and intrauterine mortality at high altitude in Bolivia. Pediatr Res. 2003; 54, 20–25.CrossRefGoogle ScholarPubMed
64. Genbacev, O, Zhou, Y, Ludlow, JW, Fisher, SJ. Regulation of human placental development by oxygen tension. Science. 1997; 277, 1669–1672.CrossRefGoogle ScholarPubMed
65. Kingdom, JCP, Kaufmann, P. Oxygen and placental villous development: origins of fetal hypoxia. Placenta. 1997; 18, 613–621.CrossRefGoogle ScholarPubMed
66. Rodesch, F, Simon, P, Donner, C, Jauniaux, E. Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy. Obstet Gynecol. 1992; 80, 283–285.Google ScholarPubMed
67. Phillips, TJ, Scott, H, Menassa, DA, et al. Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development. Sci Rep. 2017; 7, 9079.CrossRefGoogle ScholarPubMed
68. Fatemi, SH, Folsom, TD. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr Bull. 2009; 35, 528–548.CrossRefGoogle ScholarPubMed
69. Sharma, SK, Lucitti, JL, Nordman, C, et al. Impact of hypoxia on early chick embryo growth and cardiovascular function. Pediatr Res. 2006; 59, 116–120.CrossRefGoogle ScholarPubMed
70. Tintu, A, Rouwet, E, Verlohren, S, et al. Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences. PLoS One. 2009; 4, e5155.CrossRefGoogle ScholarPubMed
71. Hauton, D. Hypoxia in early pregnancy induces cardiac dysfunction in adult offspring of Rattus norvegicus, a non-hypoxia-adapted species. Comp Biochem Physiol A: Mol Integr Physiol. 2012; 163, 278–285.CrossRefGoogle ScholarPubMed
72. Ream, M, Ray, AM, Chandra, R, Chikaraishi, DM. Early fetal hypoxia leads to growth restriction and myocardial thinning. Am J Physiol Regul Integr Comp Physiol. 2008; 295, R583–R595.CrossRefGoogle ScholarPubMed
73. Rosario, GX, Konno, T, Soares, MJ. Maternal hypoxia activates endovascular trophoblast cell invasion. Dev Biol. 2008; 314, 362–375.CrossRefGoogle ScholarPubMed
74. Ain, R, Dai, G, Dunmore, JH, Godwin, AR, Soares, MJ. A prolactin family paralog regulates reproductive adaptations to a physiological stressor. Proc Natl Acad Sci USA. 2004; 101, 16543–16548.CrossRefGoogle ScholarPubMed
75. Schäffer, L, Vogel, J, Breymann, C, Gassmann, M, Marti, HH. Preserved placental oxygenation and development during severe systemic hypoxia. Am J Physiol Regul Integr Comp Physiol. 2006; 290, R844–R851.CrossRefGoogle ScholarPubMed
76. Higgins, JS, Vaughan, OR, Fernandez de Liger, E, Fowden, AL, Sferruzzi-Perri, AN. Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy. J Physiol. 2016; 594, 1341–1356.CrossRefGoogle ScholarPubMed
77. Nuzzo, AM, Camm, EJ, Sferruzzi-Perri, AN, et al. Placental Adaptation to Early-Onset Hypoxic Pregnancy and Mitochondria-Targeted Antioxidant Therapy in a Rodent Model. Am J Pathol. 2018; 188, 2704–2716.CrossRefGoogle Scholar
78. Camm, EJ, Hansell, JA, Kane, AD, et al. Partial contributions of developmental hypoxia and undernutrition to prenatal alterations in somatic growth and cardiovascular structure and function. Am J Obstet Gynecol. 2010; 203, 495.e424–495.e434.CrossRefGoogle ScholarPubMed
79. Hutter, D, Kingdom, J, Jaeggi, E. Causes and Mechanisms of Intrauterine Hypoxia and Its Impact on the Fetal Cardiovascular System: A Review, International Journal of Pediatrics. 2010, 401323.CrossRefGoogle Scholar
80. Jauniaux, E, Greenwold, N, Hempstock, J, Burton, GJ. Comparison of ultrasonographic and Doppler mapping of the intervillous circulation in normal and abnormal early pregnancies. Fertil Steril. 2003; 79, 100–106.CrossRefGoogle ScholarPubMed
81. Jauniaux, E, Watson, AL, Hempstock, J, et al. Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure. Am J Pathol. 2000; 157, 2111–2122.CrossRefGoogle ScholarPubMed
82. Watson, AL, Skepper, JN, Jauniaux, E, Burton, GJ. Susceptibility of human placental syncytiotrophoblastic mitochondria to oxygen-mediated damage in relation to gestational age 1. J Clin Endocrinol Metab. 1998; 83, 1697–1705.Google Scholar
83. Xiao, D, Liu, Y, Pearce, WJ, Zhang, L. Endothelial nitric oxide release in isolated perfused ovine uterine arteries: effect of pregnancy. Eur J Pharmacol. 1999; 367, 223–230.CrossRefGoogle ScholarPubMed
84. Magness, RR, Sullivan, JA, Li, Y, Phernetton, TM, Bird, IM. Endothelial vasodilator production by uterine and systemic arteries. VI. Ovarian and pregnancy effects on eNOS and NOx. Am J Physiol-Heart Circ Physiol. 2001; 280, H1692–H1698.CrossRefGoogle Scholar
85. Bird, IM, Zhang, L, Magness, RR. Possible mechanisms underlying pregnancy-induced changes in uterine artery endothelial function. Am J Physiol Regul Integr Comp Physiol. 2003; 284, R245–R258.CrossRefGoogle ScholarPubMed
86. Thakor, AS, Herrera, EA, Serón-Ferré, M, Giussani, DA. Melatonin and vitamin C increase umbilical blood flow via nitric oxide-dependent mechanisms. J Pineal Res. 2010; 49, 399–406.CrossRefGoogle ScholarPubMed
87. Herrera, EA, Kane, AD, Hansell, JA, et al. A role for xanthine oxidase in the control of fetal cardiovascular function in late gestation sheep. J Physiol. 2012; 590(Pt 8), 1825–1837.CrossRefGoogle ScholarPubMed
88. Kusinski, LC, Stanley, JL, Dilworth, MR, et al. eNOS knockout mouse as a model of fetal growth restriction with an impaired uterine artery function and placental transport phenotype. Am J Physiol Regul Integr Comp Physiol. 2012; 303, R86–R93.CrossRefGoogle ScholarPubMed
89. Matsubara, K, Higaki, T, Matsubara, Y, Nawa, A. Nitric oxide and reactive oxygen species in the pathogenesis of preeclampsia. Int J Mol Sci. 2015; 16, 4600–4614.CrossRefGoogle ScholarPubMed
90. Thompson, LP, Dong, Y. Chronic hypoxia decreases endothelial nitric oxide synthase protein expression in fetal guinea pig hearts. J Soc Gynecol Investig. 2005; 12, 388–395.CrossRefGoogle ScholarPubMed
91. Fish, JE, Yan, MS, Matouk, CC, et al. Hypoxic repression of endothelial nitric-oxide synthase transcription is coupled with eviction of promoter histones. J Biol Chem. 2010; 285, 810–826.CrossRefGoogle ScholarPubMed
92. Kossenjans, W, Eis, A, Sahay, R, Brockman, D, Myatt, L. Role of peroxynitrite in altered fetal-placental vascular reactivity in diabetes or preeclampsia. Am J Physiol-Heart Circ Physiol. 2000; 278, H1311–H1319.CrossRefGoogle ScholarPubMed
93. Miller, MJS, Voelker, CA, Olister, S, et al. Fetal growth retardation in rats may result from apoptosis: Role of peroxynitrite. Free Radic Biol Med. 1996; 21, 619–629.CrossRefGoogle ScholarPubMed
94. Vaziri, ND, Liang, K, Ding, Y. Increased nitric oxide inactivation by reactive oxygen species in lead-induced hypertension. Kidney Int. 1999; 56, 1492–1498.CrossRefGoogle ScholarPubMed
95. Malhotra, JD, Kaufman, RJ. Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid Redox Signal. 2007; 9, 2277–2294.CrossRefGoogle ScholarPubMed
96. Yung, H-W, Korolchuk, S, Tolkovsky, AM, Charnock-Jones, DS, Burton, GJ. Endoplasmic reticulum stress exacerbates ischemia-reperfusion-induced apoptosis through attenuation of Akt protein synthesis in human choriocarcinoma cells. The FASEB J: Official Publication of the Federation of American Societies for Experimental Biology. 2007; 21, 872–884.CrossRefGoogle ScholarPubMed
97. Giussani, DA, Camm, EJ, Niu, Y, et al. Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress. PLoS One. 2012; 7, e31017.CrossRefGoogle ScholarPubMed
98. Richter, HG, Camm, EJ, Modi, BN, et al. Ascorbate prevents placental oxidative stress and enhances birth weight in hypoxic pregnancy in rats. J Physiol. 2012; 590, 1377–1387.CrossRefGoogle ScholarPubMed
99. Aljunaidy, MM, Morton, JS, Cooke, C-LM, Davidge, ST. Prenatal hypoxia and placental oxidative stress: linkages to developmental origins of cardiovascular disease. Am J Physiol Regul Integr Comp Physiol. 2017; 313, R395–R399.CrossRefGoogle ScholarPubMed
100. Burton, GJ, Yung, HW, Murray, AJ. Mitochondrial – endoplasmic reticulum interactions in the trophoblast: stress and senescence. Placenta. 2017; 52, 146–155.CrossRefGoogle ScholarPubMed
101. Tissot van Patot, MC, Murray, AJ, Beckey, V, et al. Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning. Am J Physiol Regul Integr Comp Physiol. 2010; 298, R166–R172.CrossRefGoogle ScholarPubMed
102. Fuhrmann, DC, Brüne, B. Mitochondrial composition and function under the control of hypoxia. Redox Biol. 2017; 12, 208–215.CrossRefGoogle ScholarPubMed
103. Galkin, A, Abramov, AY, Frakich, N, Duchen, MR, Moncada, S. Lack of oxygen deactivates mitochondrial complex I: implications for ischemic injury? J Biol Chem. 2009; 284, 36055–36061.CrossRefGoogle ScholarPubMed
104. Lorca, RA, Wakle‐Prabagaran, M, Freeman, WE, Pillai, MK, England, SK. The large‐conductance voltage‐ and Ca2+‐activated K+ channel and its γ1‐subunit modulate mouse uterine artery function during pregnancy. J Physiol. 2018; 596, 1019–1033.CrossRefGoogle ScholarPubMed
105. Liu, B, Liu, Y, Shi, R, et al. Chronic prenatal hypoxia down-regulated BK channel Β1 subunits in mesenteric artery smooth muscle cells of the offspring. Cell Physiol Biochem. 2018; 45, 1603–1616.CrossRefGoogle ScholarPubMed
106. Hu, XQ, Xiao, D, Zhu, R, et al. Chronic hypoxia suppresses pregnancy-induced upregulation of large-conductance Ca2+-activated K+ channel activity in uterine arteries. Hypertension. 2012; 60, 214–222.CrossRefGoogle ScholarPubMed
107. Zhu, R, Huang, X, Hu, X-Q, Xiao, D, Zhang, L. Gestational hypoxia increases reactive oxygen species and inhibits steroid hormone-mediated upregulation of Ca(2+)-activated K(+) channel function in uterine arteries. Hypertension. 2014; 64, 415–422.CrossRefGoogle ScholarPubMed
108. Ziello, JE, Jovin, IS, Huang, Y. Hypoxia-inducible factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J Biol Med. 2007; 80, 51–60.Google ScholarPubMed
109. Iwagaki, S, Yokoyama, Y, Tang, L, et al. Augmentation of leptin and hypoxia-inducible factor 1α mRNAs in the pre-eclamptic placenta. Gynecol Endocrinol. 2004; 18, 263–268.CrossRefGoogle ScholarPubMed
110. Akhilesh, M, Mahalingam, V, Nalliah, S, et al. Hypoxia-inducible factor-1α as a predictive marker in pre-eclampsia. Biomed Rep. 2013; 1, 257–258.CrossRefGoogle ScholarPubMed
111. Rajakumar, A, Doty, K, Daftary, A, Harger, G, Conrad, KP. Impaired Oxygen-dependent Reduction of HIF-1α and -2α Proteins in Pre-eclamptic Placentae. Placenta. 2003; 24, 199–208.CrossRefGoogle ScholarPubMed
112. Caniggia, I, Winter, JL. Adriana and Luisa Castellucci Award Lecture 2001 hypoxia inducible factor-1: oxygen regulation of trophoblast differentiation in normal and pre-eclamptic pregnancies—a review. Placenta. 2002; 23, S47–S57.CrossRefGoogle ScholarPubMed
113. Bourque, SL, Davidge, ST, Adams, MA. The interaction between endothelin-1 and nitric oxide in the vasculature: new perspectives. Am J Physiol Regul Integr Comp Physiol. 2011; 300, R1288–R1295.CrossRefGoogle ScholarPubMed
114. Yanagisawa, M, Kurihara, H, Kimura, S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988; 332, 411–415.CrossRefGoogle ScholarPubMed
115. Khimji, AK, Rockey, DC. Endothelin—biology and disease. Cell Signal. 2010; 22, 1615–1625.CrossRefGoogle ScholarPubMed
116. Alonso, D, Radomski, MW. The nitric oxide-endothelin-1 connection. Heart Fail Rev. 2003; 8, 107–115.CrossRefGoogle ScholarPubMed
117. Julian, CG, Galan, HL, Wilson, MJ, et al. Lower uterine artery blood flow and higher endothelin relative to nitric oxide metabolite levels are associated with reductions in birth weight at high altitude. Am J Physiol Regul Integr Comp Physiol. 2008; 295, R906–915.CrossRefGoogle ScholarPubMed
118. Takahashi, H, Soma, S, Muramatsu, M, Oka, M, Fukuchi, Y. Upregulation of ET-1 and its receptors and remodeling in small pulmonary veins under hypoxic conditions. Am J Physiol-Lung Cell Mol Physiol. 2001; 280, L1104–L1114.CrossRefGoogle ScholarPubMed
119. Moore, LG, Shriver, M, Bemis, L, et al. Maternal adaptation to high-altitude pregnancy: an experiment of nature—a review. Placenta. 2004; 25, S60–S71.CrossRefGoogle ScholarPubMed
120. Zamudio, S, Droma, T, Norkyel, KY, et al. Protection from intrauterine growth retardation in Tibetans at high altitude. Am J Phys Anthropol. 1993; 91, 215–224.CrossRefGoogle ScholarPubMed
121. Julian, CG, Wilson, MJ, Lopez, M, et al. Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth. Am J Physiol Regul Integr Comp Physiol. 2009; 296, R1564–R1575.CrossRefGoogle ScholarPubMed
122. Giussani, DA, Phillips, PS, Anstee, S, Barker, DJP. Effects of altitude versus economic status on birth weight and body shape at birth. Pediatr Res. 2001; 49, 490–494.CrossRefGoogle ScholarPubMed
123. Soria, R, Julian, CG, Vargas, E, Moore, LG, Giussani, DA. Graduated effects of high-altitude hypoxia and highland ancestry on birth size. Pediatr Res. 2013; 74, 633–638.CrossRefGoogle ScholarPubMed
124. Wang, R. Hydrogen sulfide: the third gasotransmitter in biology and medicine. Antioxid Redox Signal. 2010; 12, 1061–1064.CrossRefGoogle ScholarPubMed
125. Gadalla, MM, Snyder, SH. Hydrogen sulfide as a gasotransmitter. J Neurochem. 2010; 113, 14–26.CrossRefGoogle ScholarPubMed
126. Forgan, LG, McNeill, BA, DeLeon, E, Gao, Y, Olson, K. Effects of hypoxia on hydrogen sulfide production and degradation gene expression pathways. FASEB J. 2017; 31(1_supplement), lb1–1091.2.Google Scholar
127. Zhao, W, Zhang, J, Lu, Y, Wang, R. The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener. EMBO J. 2001; 20, 6008–6016.CrossRefGoogle Scholar
128. Yang, G, Wu, L, Jiang, B, et al. H(2)S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine γ-lyase. Science. 2008; 322, 587–590.CrossRefGoogle Scholar
129. Lu, L, Kingdom, J, Burton, GJ, Cindrova-Davies, T. Placental stem villus arterial remodeling associated with reduced hydrogen sulfide synthesis contributes to human fetal growth restriction. Am J Pathol. 2017; 187, 908–920.CrossRefGoogle ScholarPubMed
130. Bryan, S, Yang, G, Wang, R, Khaper, N. Cystathionine gamma-lyase-deficient smooth muscle cells exhibit redox imbalance and apoptosis under hypoxic stress conditions. Exp Clin Cardiol. 2011; 16, e36–e41.Google ScholarPubMed
131. Yang, G, Pei, Y, Cao, Q, Wang, R. MicroRNA‐21 represses human cystathionine gamma‐lyase expression by targeting at specificity protein‐1 in smooth muscle cells. J Cell Physiol. 2012; 227, 3192–3200.CrossRefGoogle ScholarPubMed
132. Cindrova-Davies, T, Herrera, EA, Niu, Y, et al. Reduced cystathionine γ-lyase and increased miR-21 expression are associated with increased vascular resistance in growth-restricted pregnancies: hydrogen sulfide as a placental vasodilator. Am J Pathol. 2013; 182, 1448–1458.CrossRefGoogle ScholarPubMed
133. Wang, K, Ahmad, S, Cai, M, et al. Dysregulation of hydrogen sulfide producing enzyme cystathionine γ-lyase contributes to maternal hypertension and placental abnormalities in preeclampsia. Circulation. 2013; 127, 2514–2522.CrossRefGoogle ScholarPubMed
134. van Goor, H, van den Born, JC, Hillebrands, J-L, Joles, JA. Hydrogen sulfide in hypertension. Curr Opin Nephrol Hypertens. 2016; 25, 107–113.CrossRefGoogle ScholarPubMed
135. Tsatsaris, V, Goffin, F, Munaut, C, et al. Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences. J Clin Endocrinol Metab. 2003; 88, 5555–5563.CrossRefGoogle ScholarPubMed
136. Torry, DS, Ahn, H, Barnes, EL, Torry, RJ. Placenta growth factor: potential role in pregnancy. Am J Reprod Immunol. 1999; 41, 79–85.CrossRefGoogle ScholarPubMed
137. Li, H, Gu, B, Zhang, Y, Lewis, DF, Wang, Y. Hypoxia-induced increase in soluble Flt-1 production correlates with enhanced oxidative stress in trophoblast cells from the human placenta. Placenta. 2005; 26, 210–217.CrossRefGoogle ScholarPubMed
138. Zhou, Y, McMaster, M, Woo, K, et al. Vascular endothelial growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. Am J Pathol. 2002; 160, 1405–1423.CrossRefGoogle ScholarPubMed
139. Dongó, E, Beliczai-Marosi, G, Dybvig, AS, Kiss, L. The mechanism of action and role of hydrogen sulfide in the control of vascular tone. Nitric Oxide. 2018; 1, 75–81.CrossRefGoogle Scholar
140. Osmond, JM, Kanagy, NL. Modulation of hydrogen sulfide by vascular hypoxia. Hypoxia. 2014; 2, 117–126.Google ScholarPubMed
141. Al-Magableh, MR, Kemp-Harper, BK, Hart, JL. Hydrogen sulfide treatment reduces blood pressure and oxidative stress in angiotensin II-induced hypertensive mice. Hypertens Res. 2014; 38, 13–20.CrossRefGoogle ScholarPubMed
142. Vural, P. Nitric oxide/endothelin-1 in preeclampsia. Clin Chim Acta. 2002; 317, 65–70.CrossRefGoogle ScholarPubMed
143. Valensise, H, Vasapollo, B, Novelli, GP, et al. Maternal and fetal hemodynamic effects induced by nitric oxide donors and plasma volume expansion in pregnancies with gestational hypertension complicated by intrauterine growth restriction with absent end‐diastolic flow in the umbilical artery. Ultrasound Obstet Gynecol. 2008; 31, 55–64.CrossRefGoogle ScholarPubMed
144. LaMarca, B, Speed, J, Fournier, L, et al. Hypertension in response to chronic reductions in uterine perfusion in pregnant rats: effect of tumor necrosis factor-α blockade. Hypertension. 2008; 52, 1161–1167.CrossRefGoogle ScholarPubMed
145. LaMarca, BBD, Cockrell, K, Sullivan, E, Bennett, W, Granger, JP. Role of endothelin in mediating tumor necrosis factor-induced hypertension in pregnant rats. Hypertension. 2005; 46, 82–86.CrossRefGoogle ScholarPubMed
146. Tam Tam, KB, George, E, Cockrell, K, et al. Endothelin type A receptor antagonist attenuates placental ischemia–induced hypertension and uterine vascular resistance. Am J Obstet Gynecol. 2011; 204, 330.e331–330.e334.CrossRefGoogle ScholarPubMed
147. Jain, A. Endothelin-1: a key pathological factor in pre-eclampsia? Reprod BioMed Online. 2012; 25, 443–449.CrossRefGoogle ScholarPubMed
148. Holwerda, KM, Burke, SD, Faas, MM, et al. Hydrogen sulfide attenuates sFlt1-induced hypertension and renal damage by upregulating vascular endothelial growth factor. J Am Soc Nephrol: JASN. 2014; 25, 717–725.CrossRefGoogle ScholarPubMed
149. Shah, DA, Khalil, RA. Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia. Biochem Pharmacol. 2015; 95, 211–226.CrossRefGoogle ScholarPubMed
150. Tanbe, AF, Khalil, RA. Circulating and vascular bioactive factors during hypertension in pregnancy. Curr Bioact Compd. 2010; 6, 60–75.CrossRefGoogle ScholarPubMed
151. Shibuya, M. Structure and function of VEGF/VEGF-receptor system involved in angiogenesis. Cell Struct Funct. 2001; 26, 25–35.CrossRefGoogle ScholarPubMed
152. Maynard, SE, Min, J-Y, Merchan, J, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Investig. 2003; 111, 649–658.CrossRefGoogle ScholarPubMed
153. Levine, RJ, Maynard, SE, Qian, C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004; 350, 672–683.CrossRefGoogle ScholarPubMed
154. Tam, KBT, Lamarca, B, Arany, M, et al. Role of reactive oxygen species during hypertension in response to chronic antiangiogenic factor (sFlt-1) excess in pregnant rats. Am J Hypertens. 2011; 24, 110–113.CrossRefGoogle Scholar
155. Appel, S, Turnwald, E-M, Ankerne, J, et al. Hypoxia-mediated soluble fms-like tyrosine kinase 1 increase is not attenuated in interleukin 6-deficient mice. Reprod Sci. 2015; 22, 735–742.CrossRefGoogle Scholar
156. Karumanchi, SA, Bdolah, Y. Hypoxia and sFlt-1 in preeclampsia: the “chicken-and-egg” question. Endocrinology. 2004; 145, 4835–4837.CrossRefGoogle ScholarPubMed
157. Nevo, O, Lee, DK, Caniggia, I. Attenuation of VEGFR-2 expression by sFlt-1 and low oxygen in human placenta. PLoS One. 2013; 8, e81176.CrossRefGoogle ScholarPubMed
158. Sugimoto, H, Hamano, Y, Charytan, D, et al. Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria. J Biol Chem. 2003; 278, 12605–12608.CrossRefGoogle ScholarPubMed
159. Fisher, SJ. The placental problem: linking abnormal cytotrophoblast differentiation to the maternal symptoms of preeclampsia. Reprod Biol Endocrinol. 2004; 2, 53–53.CrossRefGoogle ScholarPubMed
160. Hu, T-X, Guo, X, Wang, G, et al. MiR133b is involved in endogenous hydrogen sulfide suppression of sFlt-1 production in human placenta. Placenta. 2017; 52, 33–40.CrossRefGoogle ScholarPubMed
161. Saleh, L, Vergouwe, Y, Verdonk, K, et al. The added value of the biomarkers sFlt-1, PlGF and their ratio on prediction of prolongation of pregnancy and maternal and fetal complications in (suspected) preeclampsia: angiogenic factors. Pregnancy Hypertens: An International Journal of Women’s Cardiovascular Health. 2016; 6, 149–150.CrossRefGoogle Scholar
162. Herraiz, I, Simón, E, Gómez-Arriaga, PI, et al. Angiogenesis-related biomarkers (sFlt-1/PLGF) in the prediction and diagnosis of placental dysfunction: an approach for clinical integration. Int J Mol Sci. 2015; 16, 19009–19026.CrossRefGoogle ScholarPubMed
163. Sovio, U, Gaccioli, F, Cook, E, et al. Prediction of preeclampsia using the sFlt-1:PLGF ratio: a prospective cohort study of unselected nulliparous women. Hypertension. 2017; 69, 731–738.CrossRefGoogle ScholarPubMed
164. Zeisler, H, Llurba, E, Chantraine, F, et al. Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016; 374, 13–22.CrossRefGoogle ScholarPubMed
165. Verlohren, S, Galindo, A, Schlembach, D, et al. An automated method for the determination of the sFlt-1/PIGF ratio in the assessment of preeclampsia. Am J Obstet Gynecol. 2010; 202, 161.e161–161.e111.CrossRefGoogle ScholarPubMed
166. Spradley, FT, Tan, AY, Joo, WS, et al. Placental growth factor administration abolishes placental ischemia-induced hypertension. Hypertension. 2016; 67, 740–747.CrossRefGoogle ScholarPubMed
167. Zhu, M, Ren, Z, Possomato-Vieira, JS, Khalil, RA. Restoring placental growth factor-soluble fms-like tyrosine kinase-1 balance reverses vascular hyper-reactivity and hypertension in pregnancy. Am J Physiol Regul Integr Comp Physiol. 2016; 311, R505–R521.CrossRefGoogle ScholarPubMed
168. Chau, K, Hennessy, A, Makris, A. Placental growth factor and pre-eclampsia. J Hum Hypertens. 2017; 31, 782–786.CrossRefGoogle ScholarPubMed
169. Suzuki, H, Ohkuchi, A, Matsubara, S, et al. Effect of recombinant placental growth factor 2 on hypertension induced by full-length mouse soluble fms-like tyrosine kinase 1 adenoviral vector in pregnant mice. Hypertension. 2009; 54, 1129–1135.CrossRefGoogle ScholarPubMed
170. Mittal, M, Siddiqui, MR, Tran, K, Reddy, SP, Malik, AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014; 20, 1126–1167.CrossRefGoogle ScholarPubMed
171. Gupta, SC, Hevia, D, Patchva, S, et al. Upsides and downsides of reactive oxygen species for cancer: the roles of reactive oxygen species in tumorigenesis, prevention, and therapy. Antioxid Redox Signal. 2012; 16, 1295–1322.CrossRefGoogle Scholar
172. Benyo, DF, Miles, TM, Conrad, KP. Hypoxia stimulates cytokine production by villous explants from the human placenta. J Clin Endocrinol Metab. 1997; 82, 1582–1588.Google ScholarPubMed
173. Cuffe, JSM, Holland, O, Salomon, C, Rice, GE, Perkins, AV. Review: placental derived biomarkers of pregnancy disorders. Placenta. 2017; 54, 104–110.CrossRefGoogle ScholarPubMed
174. Redman, CWG, Sargent, IL. Placental debris, oxidative stress and pre-eclampsia. Placenta. 2000; 21, 597–602.CrossRefGoogle ScholarPubMed
175. Pantham, P, Aye, ILMH, Powell, TL. Inflammation in maternal obesity and gestational diabetes mellitus. Placenta. 2015; 36, 709–715.CrossRefGoogle ScholarPubMed
176. Royle, C, Lim, S, Xu, B, et al. Effect of hypoxia and exogenous IL-10 on the pro-inflammatory cytokine TNF-α and the anti-angiogenic molecule soluble Flt-1 in placental villous explants. Cytokine. 2009; 47, 56–60.CrossRefGoogle ScholarPubMed
177. Casart, YC, Tarrazzi, K, Camejo, MI. Serum levels of interleukin-6, interleukin-1β and human chorionic gonadotropin in pre-eclamptic and normal pregnancy. Gynecol Endocrinol. 2007; 23, 300–303.CrossRefGoogle ScholarPubMed
178. Amash, A, Holcberg, G, Sapir, O, Huleihel, M. Placental secretion of interleukin-1 and interleukin-1 receptor antagonist in preeclampsia: effect of magnesium sulfate. J Interferon Cytokine Res. 2012; 32, 432–441.CrossRefGoogle ScholarPubMed
179. Cackovic, M, Buhimschi, CS, Zhao, G, et al. Fractional excretion of tumor necrosis factor-α in women with severe preeclampsia. Obstet Gynecol. 2008; 112, 93–100.CrossRefGoogle ScholarPubMed
180. Conrad, KP, Benyo, DF. Placental cytokines and the pathogenesis of preeclampsia. Am J Reprod Immunol. 1997; 37, 240–249.CrossRefGoogle ScholarPubMed
181. Bowen, RS, Gu, Y, Zhang, Y, Lewis, DF, Wang, Y. Hypoxia promotes interleukin-6 and -8 but reduces interleukin-10 production by placental trophoblast cells from preeclamptic pregnancies. J Soc Gynecol Investig. 2005; 12, 428–432.CrossRefGoogle ScholarPubMed
182. Prins, J, Gomez-Lopez, N, Robertson, S. Interleukin-6 in pregnancy and gestational disorder, Journal of Reproductive Immunology. 2012; 95, 1–14.Google Scholar
183. Pober, JS, Cotran, RS. Cytokines and endothelial cell biology. Physiol Rev. 1990; 70, 427–451.CrossRefGoogle ScholarPubMed
184. Coussons-Read, ME, Mazzeo, RS, Whitford, MH, et al. High altitude residence during pregnancy alters cytokine and catecholamine levels. Am J Reprod Immunol. 2003; 48, 344–354.CrossRefGoogle Scholar
185. LaMarca, B, Speed, J, Fournier, L, et al. Hypertension in response to chronic reductions in uterine perfusion in pregnant rats: effect of tumor necrosis factor-α blockade. Hypertension. 2008; 52, 1161–1167.CrossRefGoogle ScholarPubMed
186. Burton, GJ, Jones, CJP. Syncytial knots, sprouts, apoptosis, and trophoblast deportation from the human placenta. Taiwanese J Obstet Gynecol. 2009; 48, 28–37.CrossRefGoogle ScholarPubMed
187. Smárason, AK, Sargent, IL, Starkey, PM, Redman, CWG. The effect of placental syncytiotrophoblast microvillous membranes from normal and pre‐eclamptic women on the growth of endothelial cells in vitro. BJOG: An Int J Obstet Gynaecol. 1993; 100, 943–949.CrossRefGoogle ScholarPubMed
188. Chen, Q, Ding, JX, Liu, B, et al. Spreading endothelial cell dysfunction in response to necrotic trophoblasts. Soluble factors released from endothelial cells that have phagocytosed necrotic shed trophoblasts reduce the proliferation of additional endothelial cells. Placenta. 2010; 31, 976–981.CrossRefGoogle ScholarPubMed
189. Chen, Q, Chen, L, Liu, B, et al. The role of autocrine TGFβ1 in endothelial cell activation induced by phagocytosis of necrotic trophoblasts: a possible role in the pathogenesis of pre‐eclampsia. J Pathol. 2010; 221, 87–95.CrossRefGoogle ScholarPubMed
190. Toth, B, Lok, CAR, Böing, A, et al. Microparticles and exosomes: impact on normal and complicated pregnancy. Am J Reprod Immunol. 2007; 58, 389–402.CrossRefGoogle ScholarPubMed
191. Göhner, C, Schlembach, D, Schleussner, E, Markert, UR, Fitzgerald, JS. Hypoxia alters syncytiotrophoblastic microparticles (STBM)-related coagulation capacities. Pregnancy Hypertens: An Int J Women’s Cardiovasc Health. 2013; 3, 70.CrossRefGoogle ScholarPubMed
192. Goswami, D, Tannetta, DS, Magee, LA, et al. Excess syncytiotrophoblast microparticle shedding is a feature of early-onset pre-eclampsia, but not normotensive intrauterine growth restriction. Placenta. 2006; 27, 56–61.CrossRefGoogle Scholar
193. Germain, SJ, Sacks, GP, Soorana, SR, Sargent, IL, Redman, CW. Systemic inflammatory priming in normal pregnancy and preeclampsia: the role of circulating syncytiotrophoblast microparticles. J Immunol. 2007; 178, 5949–5956.CrossRefGoogle ScholarPubMed
194. Cockell, AP, Learmont, JG, Smárason, AK, et al. Human placental syncytiotrophoblast microvillous membranes impair maternal vascular endothelial function. BJOG: An Int J Obstet Gynaecol. 1997; 104, 235–240.CrossRefGoogle ScholarPubMed
195. Kowal, J, Tkach, M, Théry, C. Biogenesis and secretion of exosomes. Curr Opin Cell Biol. 2014; 29, 116–125.CrossRefGoogle ScholarPubMed
196. Colombo, M, Raposo, G, Théry, C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014; 30, 255–289.CrossRefGoogle ScholarPubMed
197. Sabapatha, A, Gercel-Taylor, C, Taylor, DD. Specific isolation of placenta-derived exosomes from the circulation of pregnant women and their immunoregulatory consequences. Am J Reprod Immunol. 2006; 56, 345–355.CrossRefGoogle ScholarPubMed
198. Sarker, S, Scholz-Romero, K, Perez, A, et al. Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy. J Transl Med. 2014; 12, 204.CrossRefGoogle ScholarPubMed
199. Mincheva-Nilsson, L, Baranov, V. Placenta-derived exosomes and syncytiotrophoblast microparticles and their role in human reproduction: immune modulation for pregnancy success. Am J Reprod Immunol. 2014; 72, 440–457.CrossRefGoogle ScholarPubMed
200. Salomon, C, Kobayashi, M, Ashman, K, et al. Hypoxia-induced changes in the bioactivity of cytotrophoblast-derived exosomes. PLoS One. 2013; 8, e79636.CrossRefGoogle ScholarPubMed
201. Redman, CWG, Sargent, IL. Circulating microparticles in normal pregnancy and pre-eclampsia. Placenta. 2008; 29, 73–77.CrossRefGoogle ScholarPubMed
202. Dragovic, RA, Southcombe, JH, Tannetta, DS, Redman, CWG, Sargent, IL. Multicolor flow cytometry and nanoparticle tracking analysis of extracellular vesicles in the plasma of normal pregnant and pre-eclamptic women. Biol Reprod. 2013; 89, 1–12.CrossRefGoogle ScholarPubMed
203. Baig, S, Kothandaraman, N, Manikandan, J, et al. Proteomic analysis of human placental syncytiotrophoblast microvesicles in preeclampsia. Clin Proteomics. 2014; 11, 40.CrossRefGoogle ScholarPubMed
204. Escudero C, Herlitz K, Troncoso F, et al. Role of Extracellular Vesicles and microRNAs on Dysfunctional Angiogenesis during Preeclamptic Pregnancies, Frontiers in Physiology. 2016; 7, 98.Google Scholar
205. Salomon, C, Ryan, J, Sobrevia, L, et al. Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis. PLoS One. 2013; 8, e68451.CrossRefGoogle ScholarPubMed
206. Atay, S, Gercel-Taylor, C, Suttles, J, Mor, G, Taylor, DD. Trophoblast-derived exosomes mediate monocyte recruitment and differentiation. Am J Reprod Immunol. 2011; 65, 65–77.CrossRefGoogle Scholar
207. Roberts, JM, Escudero, C. The placenta in preeclampsia. Pregnancy Hypertens. 2012; 2, 72–83.CrossRefGoogle ScholarPubMed
208. Toal, M, Chan, C, Fallah, S, et al. Usefulness of a placental profile in high-risk pregnancies. Am J Obstet Gynecol. 2007; 196, 361–363.CrossRefGoogle ScholarPubMed
209. Kliman, HJ. Uteroplacental blood flow: the story of decidualization, menstruation, and trophoblast invasion. Am J Pathol. 2000; 157, 1759–1768.CrossRefGoogle ScholarPubMed
210. Naeye, RL. Placental infarction leading to fetal or neonatal death. A prospective study. Obstet Gynecol. 1977; 50, 583–588.Google ScholarPubMed
211. Soma, H, Yoshida, K, Mukaida, T, Tabuchi, Y. Morphologic changes in the hypertensive placenta. Contrib Gynecol Obstet. 1982; 9, 58–75.CrossRefGoogle ScholarPubMed
212. Stanek, J. Hypoxic patterns of placental injury: a review. Arch Pathol Lab Med. 2013; 137, 706–720.CrossRefGoogle ScholarPubMed
213. Baergen, RN. Manual of Pathology of the Human Placenta, 2nd edn, 2011. Springer: USA.CrossRefGoogle Scholar
214. Giussani, DA, Salinas, CE, Villena, M, Blanco, CE. The role of oxygen in prenatal growth: studies in the chick embryo. J Physiol. 2007; 585(Pt 3), 911–917.CrossRefGoogle ScholarPubMed
215. Mehta, AR, Mehta, PR. The hypoxia of high altitude causes restricted fetal growth in chick embryos with the extent of this effect depending on maternal altitudinal status. J Physiol. 2008; 586, 1469–1471.CrossRefGoogle ScholarPubMed
216. Giussani, DA. The fetal brain sparing response to hypoxia: physiological mechanisms. J Physiol. 2016; 594, 1215–1230.CrossRefGoogle ScholarPubMed
217. Mulder, AL, van Golde, JC, Prinzen, FW, Blanco, CE. Cardiac output distribution in response to hypoxia in the chick embryo in the second half of the incubation time. J Physiol. 1998; 508((Pt 1)), 281–287.CrossRefGoogle ScholarPubMed
218. Mulder, ALM, Miedema, A, De Mey, JGR, Giussani, DA, Blanco, CE. Sympathetic control of the cardiovascular response to acute hypoxemia in the chick embryo. Am J Physiol Regul Integr Comp Physiol. 2002; 282, R1156–R1163.CrossRefGoogle ScholarPubMed
219. Salinas, CE, Blanco, CE, Villena, M, et al. Cardiac and vascular disease prior to hatching in chick embryos incubated at high altitude. J Dev Orig Health Dis. 2010; 1, 60–66.CrossRefGoogle ScholarPubMed
220. Herrera, EA, Salinas, CE, Blanco, CE, Villena, M, Giussani, DA. High altitude hypoxia and blood pressure dysregulation in adult chickens. J Dev Orig Health Dis. 2013; 4, 69–76.CrossRefGoogle ScholarPubMed
221. Salinas, CE, Blanco, CE, Villena, M, Giussani, DA. High-altitude hypoxia and echocardiographic indices of pulmonary hypertension in male and female chickens at adulthood. Circ J. 2014; 78, 1459–1464.CrossRefGoogle ScholarPubMed
222. Itani, N, Skeffington, KL, Beck, C, Giussani, DA. Sildenafil therapy for fetal cardiovascular dysfunction during hypoxic development: studies in the chick embryo. J Physiol. 2017; 595, 1563–1573.CrossRefGoogle ScholarPubMed
223. Itani, N, Skeffington, KL, Beck, C, Niu, Y, Giussani, DA. Melatonin rescues cardiovascular dysfunction during hypoxic development in the chick embryo. J Pineal Res. 2016; 60, 16–26.CrossRefGoogle ScholarPubMed
224. Metcalfe, J, Stock, MK. Oxygen exchange in the chorioallantoic membrane, avian homologue of the mammalian placenta. Placenta. 1993; 14, 605–613.CrossRefGoogle ScholarPubMed