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Increased apoptosis in first trimester extravillous trophoblasts from pregnancies at higher risk of developing preeclampsia

Whitley, GSJ; Dash, PR; Ayling, L-J; Prefumo, F; Thilaganathan, B; Cartwright, JE (2007) Increased apoptosis in first trimester extravillous trophoblasts from pregnancies at higher risk of developing preeclampsia. AMERICAN JOURNAL OF PATHOLOGY, 170 (6). 1903 - 1909 (7). ISSN 0002-9440 https://doi.org/10.2353/ajpath.2007.070006

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Abstract

Preeclampsia complicates 5 to 10% of pregnancies and is a leading cause of maternal and fetal mortality and morbidity. Although the cause is unknown, inadequate invasion and remodeling of maternal uterine arteries by extravillous trophoblasts (EVTs) in the first trimester is a common feature. Uterine spiral artery resistance as detected by Doppler ultrasound is commonly used in the second trimester to identify pregnancies destined to develop preeclampsia. Correlation between high uterine resistance and the failure of trophoblast invasion has been reported as early as 12 weeks. However, the reason for this failure has not been established. Under standing the processes involved would significantly improve our diagnostic potential. In this study, we correlated increased first trimester uterine artery resistance with a biological abnormality in trophoblast function. EVTs derived from high-resistance pregnancies were more sensitive to apoptotic stimuli than those from normal-resistance pregnancies. Survival of EVTs from high-resistance pregnancies could be increased by nitric oxide, whereas inhibition of nitric oxide in cells from normal-resistance pregnancies increased apoptotic sensitivity. This predates the onset of symptoms by several weeks and provides evidence for a mechanism responsible for the incomplete uterine vessel remodeling and the differences in artery resistance between preeclamptic and normal pregnancies.

Item Type: Article
Additional Information: PubMed ID: 17525258
Keywords: Apoptosis, Arteries, Female, Fetal Mortality, Humans, Pre-Eclampsia, Pregnancy, Pregnancy Trimester, First, Risk Factors, Trophoblasts, Ultrasonography, Doppler, Uterus, Vascular Resistance, Science & Technology, Life Sciences & Biomedicine, Pathology, UTERINE ARTERY DOPPLER, NITRIC-OXIDE SYNTHASE, NECROSIS-FACTOR-ALPHA, INTRAUTERINE GROWTH-RETARDATION, DECIDUAL SPIRAL ARTERIES, PLASMA-CONCENTRATIONS, HUMAN PLACENTA, IN-VITRO, ASYMMETRIC DIMETHYLARGININE, ENDOGENOUS INHIBITOR
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Journal or Publication Title: AMERICAN JOURNAL OF PATHOLOGY
ISSN: 0002-9440
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Dates:
DateEvent
1 June 2007Published
Web of Science ID: WOS:000246955300010
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URI: http://openaccess.sgul.ac.uk/id/eprint/2484
Publisher's version: https://doi.org/10.2353/ajpath.2007.070006

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