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Adoptive transfer of placental ischemia‐stimulated natural killer cells causes a preeclampsia‐like phenotype in pregnant rats
Author(s) -
Travis Olivia K.,
Baik Cedar,
Tardo Geilda A.,
Amaral Lorena,
Jackson Carmilya,
Greer Mallory,
Giachelli Chelsea,
Ibrahim Tarek,
Herrock Owen T.,
Williams Jan M.,
Cornelius Denise C.
Publication year - 2021
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.13386
Subject(s) - preeclampsia , medicine , endocrinology , fetus , blood pressure , pathophysiology , gestation , pregnancy , biology , genetics
Problem The Reduced Uterine Perfusion Pressure (RUPP) rat model of placental ischemia recapitulates many characteristics of preeclampsia including maternal hypertension, intrauterine growth restriction (IUGR), and increased cytolytic natural killer cells (cNKs). While we have previously shown a 5‐fold higher cytotoxicity of RUPP NKs versus normal pregnant NKs, their role in RUPP pathophysiology remains unclear. In this study, we tested the hypotheses that (1) adoptive transfer of RUPP‐stimulated NKs will induce maternal hypertension and IUGR in normal pregnant control (Sham) rats and (2) adoptive transfer of Sham NKs will attenuate maternal hypertension and IUGR in RUPP rats. Method of Study On gestation day (GD)14, vehicle or 5 × 10 6 RUPP NKs were infused i.v. into a subset of Sham rats (Sham+RUPP NK), and vehicle or 5 × 10 6 Sham NKs were infused i.v. into a subset of RUPP rats (RUPP+Sham NK; n = 12/group). On GD18, Uterine Artery Resistance Index (UARI) was measured. On GD19, mean arterial pressure (MAP) was measured, animals were sacrificed, and blood and tissues were collected for analysis. Results Adoptive transfer of RUPP NKs into Sham rats resulted in elevated NK activation, UARI, placental oxidative stress, and preproendothelin expression as well as reduced circulating nitrate/nitrite. This led to maternal hypertension and IUGR. RUPP recipients of Sham NKs demonstrated normalized NK activation, sFlt‐1, circulating and placental VEGF, and UARI, which led to improved maternal blood pressure and normal fetal growth. Conclusion These data suggest a direct role for cNKs in causing preeclampsia pathophysiology and a role for normal NKs to improve maternal outcomes and IUGR during late gestation.