Abstract 578: Depletion Of Natural Killer Cells Is Associated With Deterioration Of Fetal Outcome In A Transgenic Rat Model For Preeclampsia
Introduction: Preeclampsia is defined by maternal hypertension and proteinuria developed during pregnancy. It is associated with fetal growth restriction and diminished trophoblast cell invasion into uterus. Uterine natural killer cells are the most abundant leukocytes during early pregnancy. They are considered as regulators of placentation and remodeling of spiral arteries. However, their precise function remains still unclear and is contradictory. It has been shown that depletion of natural killer cells increases number of invasive trophoblast cells in healthy pregnant rats. We tested the hypothesis whether depletion of natural killer cells improves maternal symptoms and fetal outcome in preeclamptic rats.
Material and Methods: We have developed and characterized a transgenic rat model for preeclampsia. After a female rat expressing the human angiotensinogen has been mated with a male transgenic for the human renin, the female develops hypertension and proteinuria during pregnancy. Its fetuses are growth restricted. Within this rat model, we depleted natural killer cells with the antibody anti-asialo GM1 according to a published protocol (intraperitoneal injections on day 5 and day 10 of pregnancy). We analyzed 7 preeclamptic rats with in total 72 fetuses receiving anti-asialo GM1 and 5 control rats with in total 54 fetuses receiving rabbit serum. Rats were culled at end of pregnancy (day 21).
Results: Successful depletion of natural killer cells was shown by flow cytometry of the spleen and mRNA analysis of the uterus. Application of anti-asialo GM1 had no influence on blood pressure (158±8mmHg control group vs. 155±8mmHg anti-asialo GM1 group, mean arterial pressure on day 17, measured by telemetry), proteinuria (7.0±5.1mg/24hrs control group vs. 16.2±10.0mg/24hrs anti-asialo GM1 group), and fetal weight (2.9±0.6g control group vs. 2.7±0.5g anti-asialo GM1 group). However, fetal brain/liver weight ratio as a marker of intrauterine growth retardation was increased by 22% in fetuses of the anti-asialo GM1 group (0.9±0.2 control group vs. 1.1±0.4 anti-asialo GM1 group, p=0.02).
Conclusion: Depletion of natural killer cells is not associated with altered maternal symptoms of the preeclamptic phenotype, but with deterioration of fetal outcome.
Author Disclosures: M. Golic: None. N. Haase: None. F. Herse: None. L. Przybyl: None. S. Verlohren: None. W. Henrich: None. D.N. Müller: None. R. Dechend: None.
- © 2014 by American Heart Association, Inc.