title: Analysis of maternal and fetal cardiovascular systems during hyperglycemic pregnancy in the nonobese diabetic mouse.
abstract: Preconception or gestationally induced diabetes increases morbidities and elevates long-term cardiovascular disease risks in women and their children. Spontaneously hyperglycemic (d)-NOD/ShiLtJ female mice, a type 1 diabetes model, develop bradycardia and hypotension after midpregnancy compared with normoglycemic, age- and gestational day (GD)-matched control (c-NOD) females. We hypothesized that onset of the placental circulation at GD 9-10 and rapid fetal growth from GD 14 correlate with aberrant hemodynamic outcomes in d-NOD females. To develop further gestational time-course correlations between maternal cardiac and renal parameters, high-frequency ultrasonography was applied to d- and c-NOD mice (virgin and at GD 8-16). Cardiac output and left ventricular (LV) mass increased in c-NOD but not in d-NOD mice. Ultrasound and postmortem histopathology showed overall greater LV dilation in d-NOD than in c-NOD mice at mid to late gestation. These changes suggest blunted remodeling and altered functional adaptation of d-NOD hearts. Umbilical cord ultrasounds revealed lower fetal heart rates from GD 12 and lower umbilical flow velocities at GD 14 and GD 16 in d-NOD versus c-NOD pregnancies. From GD 14 to GD 16, d-NOD fetal losses exceeded c-NOD fetal losses. Similar aberrant responses in pregnancies of women with diabetes may elevate postpartum maternal and child cardiovascular risk, particularly if mothers lack adequate prenatal care or have poor glycemic control during gestation.
authors: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors: Kristiina L
authors: KL
authors: Aasa
authors: Kenneth K
authors: KK
authors: Kwong
authors: Michael A
authors: MA
authors: Adams
authors: B Anne
authors: BA
authors: Croy
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002302:Cardiac Output / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D016640:Diabetes, Gestational / Q000503:physiopathology*; D004452:Echocardiography; D005260:Female; D005312:Fetal Blood / Q000502:physiology; D047109:Fetal Development / Q000502:physiology; D006321:Heart / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology; D051379:Mice; D016688:Mice, Inbred NOD; D011247:Pregnancy; D012307:Risk Factors; D020257:Ventricular Remodeling / Q000502:physiology*
keywords: NOD mouse; cardiac adaptations; cardiovascular; cardiovascular system; developmental origins of health and disease; diabetes; pregnancy
references: N Engl J Med. 2005 Jun 16;352(24):2477-86
references: 15951574
references: World J Diabetes. 2011 Nov 15;2(11):196-203
references: 22087356
references: Birth Defects Res A Clin Mol Teratol. 2009 Jun;85(6):523-30
references: 19180650
references: Hypertens Pregnancy. 2011;30(3):243-59
references: 21740248
references: Circulation. 2002 Dec 3;106(23):2986-92
references: 12460884
references: Ultrasound Obstet Gynecol. 2005 May;25(5):444-53
references: 15816007
references: Blood. 2011 May 12;117(19):5231-42
references: 21389321
references: Yonsei Med J. 2009 Feb 28;50(1):39-44
references: 19259346
references: Int J Clin Exp Med. 2011;4(4):258-64
references: 22140597
references: Am J Obstet Gynecol. 1990 Mar;162(3):841-7
references: 2316595
references: Curr Cardiol Rep. 2010 May;12(3):250-6
references: 20424969
references: Diabetes. 2007 Dec;56(12):2919-26
references: 17827401
references: Am J Obstet Gynecol. 2008 Sep;199(3):278.e1-5
references: 18771982
references: Diabetes Care. 2011 Aug;34(8):1683-8
references: 21636798
references: BMJ. 2004 Apr 17;328(7445):915
references: 15066886
references: Circ Res. 2000 Dec 8;87(12):1123-32
references: 11110769
references: Diabet Med. 2002 Mar;19(3):216-20
references: 11918624
references: Dev Biol. 2002 Oct 15;250(2):358-73
references: 12376109
references: Am J Physiol Renal Physiol. 2011 Jun;300(6):F1271-82
references: 21367916
references: Diabetes Care. 2007 Jul;30 Suppl 2:S225-35
references: 17596477
references: Biol Reprod. 2011 Sep;85(3):605-14
references: 21613629
references: J Clin Endocrinol Metab. 2005 Jun;90(6):3225-9
references: 15797952
references: Acta Diabetol. 2011 Sep;48(3):173-81
references: 20198391
references: Endocrinol Metab Clin North Am. 2011 Dec;40(4):727-38
references: 22108277
references: Am J Physiol Heart Circ Physiol. 2009 Feb;296(2):H380-8
references: 19060130
references: Auton Neurosci. 2008 Feb 29;138(1-2):108-13
references: 18166503
references: Arterioscler Thromb Vasc Biol. 2004 Apr;24(4):721-6
references: 14962949
references: Endocrinology. 2006 Nov;147(11):5126-31
references: 16873529
references: Lab Invest. 2000 Apr;80(4):513-27
references: 10780668
references: J Clin Endocrinol Metab. 2005 Jul;90(7):3983-8
references: 15840749
references: Obstet Gynecol. 2004 Jul;104(1):20-9
references: 15228996
references: J Surg Res. 2011 Jun 15;168(2):e195-202
references: 21470634
references: Semin Fetal Neonatal Med. 2009 Apr;14(2):119-24
references: 19208505
references: Placenta. 2011 Dec;32(12):949-55
references: 22014504
references: Br Heart J. 1992 Dec;68(6):540-3
references: 1467047
references: Diabetes Care. 1986 Jul-Aug;9(4):376-83
references: 3527613
references: Diabetes Res Clin Pract. 2009 Jul;85(1):14-9
references: 19446355
references: Ultrasound Obstet Gynecol. 2011 Sep;38(3):325-31
references: 21538641
references: Ther Adv Cardiovasc Dis. 2008 Aug;2(4):249-59
references: 19124425
references: Am J Physiol Heart Circ Physiol. 2006 Sep;291(3):H1421-8
references: 16603699
references: Curr Pharm Des. 2010;16(26):2929-34
references: 20632954
references: Reprod Sci. 2013 Jul;20(7):781-90
references: 23269095
references: Curr Diab Rep. 2012 Feb;12(1):4-15
references: 22094826