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Vasopressin infusion throughout pregnancy causes placental pathology in mice consistent with preeclampsia
Author(s) -
GibsonCorley Katherine N.,
Sandgren Jeremy A.,
Perschbacher Katherine J.,
Zhang Shao Y.,
Deng Guorui,
Santillan Donna A.,
Santillan Mark K.,
Grobe Justin L.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.676.11
Subject(s) - preeclampsia , endocrinology , vasopressin , medicine , spiral artery , intrauterine growth restriction , placenta , umbilical artery , uterine artery , oxytocin , saline , gestation , decidua , pregnancy , fetus , biology , genetics
Human preeclampsia (PE) is associated with elevated secretion of arginine vasopressin (AVP), and chronic infusion of AVP into pregnant mice is sufficient to model PE by causing hypertension, renal glomerular endotheliosis, proteinuria, fetal placental hypoxia, and growth restriction. Early stages of PE are associated with defective trophoblast invasion of maternal spiral arteries, leading to decreased artery diameter and placental oxygenation. AVP infusion (24 ng/hr, sc) reduced placental growth factor mRNA and protein at gestational day (GD) 17.5. Therefore, we performed histopathologic analyses of placentas collected from mice at GD12.5 infused with saline or AVP, with the hypothesis that AVP leads to early placental PE phenotypes. This preliminary cohort demonstrated an increased urine protein content (saline n=7 27.1±2.7, AVP n=11 44.1±2.5 mg/mL; p<0.01), trends toward elevated mid‐gestational systolic blood pressure (104±2.1, 110±2.2 mmHg; p=0.09), and similar changes in heart rate (Δ from baseline: 37.1±15.5, 38.8±11.8 bpm; p=0.93). GD12.5 placentas were then routinely processed and stained with HE or cytokeratin‐8 to examine morphological changes induced by AVP. AVP infusion had no significant effects junctional zone (saline n=11 383±18, AVP n=13 376±15 μm; p=0.76) or decidua layer (652±21, 585±33 μm; p=0.12) thicknesses but significantly reduced labyrinth layer thickness (727±26, 640±13 μm; p<0.05). AVP caused a reduction in average maximum spiral artery diameter within the decidua (161±12, 125±7 μm; p<0.05) and reduced total spiral artery number (8.1±0.8, 4.8±0.4, p<0.01), but no difference in the maximum invasion depth of CK8‐positive trophoblasts (348±22, 302±23 μm; p=0.16). We conclude that AVP infusion is sufficient to induce key mid‐gestational features of PE in pregnant mice, including reduced spiral artery diameter. Such morphological changes may be associated with the reduced placental growth factor expression in this model. Support or Funding Information National Institutes of Health (GM067795, HL134850, HL084207), the American Heart Association (13SDG143400012, 15SFRN23480000, 15SFRN23730000, 15SFRN23760002, 15SFRN23860007, 16PRE30980043, 15UFEL25850040, 14PRE20380401), the American Physiological Society (UGREF & UGSRF programs), University of Iowa Center for Hypertension Research, and the Roy J. Carver Trust. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .