title: Computational Fluid Dynamic Simulations of Maternal Circulation: Wall Shear Stress in the Human Placenta and Its Biological Implications.
abstract: BACKGROUND
  In the human placenta the maternal blood circulates in the intervillous space (IVS). The syncytiotrophoblast (STB) is in direct contact with maternal blood. The wall shear stress (WSS) exerted by the maternal blood flow on the STB has not been evaluated. Our objective was to determine the physiological WSS exerted on the surface of the STB during the third trimester of pregnancy.
  
  
  METHODS
  To gain insight into the shear stress levels that the STB is expected to experience in vivo, we have formulated three different computational models of varying levels of complexity that reflect different physical representations of the IVS. Computations of the flow fields in all models were performed using the CFD module of the finite element code COMSOL Multiphysics 4.4. The mean velocity of maternal blood in the IVS during the third trimester was measured in vivo with dynamic MRI (0.94±0.14 mm.s-1). To investigate if the in silico results are consistent with physiological observations, we studied the cytoadhesion of human parasitized (Plasmodium falciparum) erythrocytes to primary human STB cultures, in flow conditions with different WSS values.
  
  
  RESULTS
  The WSS applied to the STB is highly heterogeneous in the IVS. The estimated average values are relatively low (0.5±0.2 to 2.3±1.1 dyn.cm-2). The increase of WSS from 0.15 to 5 dyn.cm-2 was associated with a significant decrease of infected erythrocyte cytoadhesion. No cytoadhesion of infected erythrocytes was observed above 5 dyn.cm-2 applied for one hour.
  
  
  CONCLUSIONS
  Our study provides for the first time a WSS estimation in the maternal placental circulation. In spite of high maternal blood flow rates, the average WSS applied at the surface of the chorionic villi is low (<5 dyn.cm-2). These results provide the basis for future physiologically-relevant in vitro studies of the biological effects of WSS on the STB.
authors.affiliation: INSERM, UMR-S 1139, Paris, France.|PRES Sorbonne Paris Cité, Université Paris Descartes, Paris, France.|Port Royal Maternity, Department of Gynecology Obstetrics I, Centre Hospitalier Universitaire Cochin Broca Hôtel Dieu, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpital de Paris, Paris, France.|DHU Risques et grossesse, Paris, France.|PremUP Foundation, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Lecarpentier
authors.affiliation: Laboratoire d'Hydrodynamique (LadHyX), CNRS, École Polytechnique, 91128, Palaiseau, France.
authors.forename: M
authors.initials: M
authors.lastname: Bhatt
authors.affiliation: Institut de Recherche pour le Développement (IRD), MERIT - UMR216, Paris, France.
authors.forename: G I
authors.initials: GI
authors.lastname: Bertin
authors.affiliation: PRES Sorbonne Paris Cité, Université Paris Descartes, Paris, France.|INSERM U970, Paris Cardiovascular Research Center-PARCC, Paris, France.|EA FETUS 7328, Paris, France.|Department of Obstetrics and Fetal Medicine, Paris Descartes University, Hôpital Necker-Enfants-Malades, Assistance Publique-Hôpital de Paris, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Deloison
authors.affiliation: PRES Sorbonne Paris Cité, Université Paris Descartes, Paris, France.|INSERM U970, Paris Cardiovascular Research Center-PARCC, Paris, France.|EA FETUS 7328, Paris, France.|Department of Obstetrics and Fetal Medicine, Paris Descartes University, Hôpital Necker-Enfants-Malades, Assistance Publique-Hôpital de Paris, Paris, France.
authors.forename: L J
authors.initials: LJ
authors.lastname: Salomon
authors.affiliation: Institut de Recherche pour le Développement (IRD), MERIT - UMR216, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Deloron
authors.affiliation: INSERM, UMR-S 1139, Paris, France.|PRES Sorbonne Paris Cité, Université Paris Descartes, Paris, France.|DHU Risques et grossesse, Paris, France.|PremUP Foundation, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Fournier
authors.affiliation: Laboratoire d'Hydrodynamique (LadHyX), CNRS, École Polytechnique, 91128, Palaiseau, France.
authors.forename: A I
authors.initials: AI
authors.lastname: Barakat
authors.affiliation: INSERM, UMR-S 1139, Paris, France.|PRES Sorbonne Paris Cité, Université Paris Descartes, Paris, France.|Port Royal Maternity, Department of Gynecology Obstetrics I, Centre Hospitalier Universitaire Cochin Broca Hôtel Dieu, Groupe Hospitalier Universitaire Ouest, Assistance Publique-Hôpital de Paris, Paris, France.|DHU Risques et grossesse, Paris, France.|PremUP Foundation, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Tsatsaris
mesh_terms: D001783:Blood Flow Velocity / Q000502:physiology; D003198:Computer Simulation; D004912:Erythrocytes / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D057446:Hydrodynamics; D008954:Models, Biological; D010920:Placenta / Q000098:blood supply / Q000502:physiology*; D011247:Pregnancy; D033081:Shear Strength; D013314:Stress, Mechanical
references.citation: Infect Immun. 2006 May;74(5):3035-8
references.pmid: 16622246
references.citation: Biorheology. 2005;42(6):493-509
references.pmid: 16369086
references.citation: Am J Physiol Heart Circ Physiol. 2007 Mar;292(3):H1209-24
references.pmid: 17098825
references.citation: Placenta. 2009 Jun;30(6):473-82
references.pmid: 19375795
references.citation: Circ J. 2009 Nov;73(11):1983-92
references.pmid: 19801852
references.citation: Placenta. 2010 Jan;31(1):44-52
references.pmid: 19945160
references.citation: Placenta. 2010 Jul;31(7):602-6
references.pmid: 20444500
references.citation: Ultrasound Obstet Gynecol. 2012 Aug;40(2):171-8
references.pmid: 22102536
references.citation: Rev Bras Ginecol Obstet. 2013 Jul;35(7):317-22
references.pmid: 24080844
references.citation: Infect Immun. 1999 Dec;67(12):6596-602
references.pmid: 10569780
references.citation: Am J Pathol. 2000 Dec;157(6):2111-22
references.pmid: 11106583
references.citation: Biorheology. 2001;38(2-3):119-42
references.pmid: 11381170
references.citation: Am J Physiol Heart Circ Physiol. 2001 Aug;281(2):H796-803
references.pmid: 11454584
references.citation: J Cell Sci. 2003 Aug 15;116(Pt 16):3413-21
references.pmid: 12840075
references.citation: Science. 1976 Aug 20;193(4254):673-5
references.pmid: 781840
references.citation: J Biomech. 1977;10(11/12):807-14
references.pmid: 606727
references.citation: Biochem J. 1986 Jan 15;233(2):351-6
references.pmid: 3954740
references.citation: Placenta. 1986 Mar-Apr;7(2):111-20
references.pmid: 3725743
references.citation: Placenta. 1986 Mar-Apr;7(2):95-110
references.pmid: 3725748
references.citation: J Cell Physiol. 1993 Jan;154(1):122-8
references.pmid: 8419399
references.citation: J Cell Biol. 1995 Dec;131(5):1231-42
references.pmid: 8522586
references.citation: Science. 1996 Jun 7;272(5267):1502-4
references.pmid: 8633247
references.citation: J Perinat Med. 1997;25(4):373-80
references.pmid: 9350609
references.citation: J Biol Chem. 1998 Nov 6;273(45):29972-8
references.pmid: 9792717
references.citation: Lancet Infect Dis. 2007 Feb;7(2):105-17
references.pmid: 17251081