title: Increased apoptosis in first trimester extravillous trophoblasts from pregnancies at higher risk of developing preeclampsia.
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. Understanding 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.
authors.affiliation: Developmental and Endocrine Signalling Centre, Division of Basic Medical Sciences, St. George's, University of London, Cranmer Terrace, London, UK. g.whitley@sgul.ac.uk
authors.forename: Guy St J
authors.initials: GS
authors.lastname: Whitley
authors.forename: Philip R
authors.initials: PR
authors.lastname: Dash
authors.forename: Laura-Jo
authors.initials: LJ
authors.lastname: Ayling
authors.forename: Federico
authors.initials: F
authors.lastname: Prefumo
authors.forename: Baskaran
authors.initials: B
authors.lastname: Thilaganathan
authors.forename: Judith E
authors.initials: JE
authors.lastname: Cartwright
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001158:Arteries / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D046689:Fetal Mortality; D006801:Humans; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012307:Risk Factors; D014327:Trophoblasts / Q000502:physiology*; D018608:Ultrasonography, Doppler; D014599:Uterus / Q000098:blood supply*; D014655:Vascular Resistance