title: Increased apoptosis, altered oxygen signaling, and antioxidant defenses in first-trimester pregnancies with high-resistance uterine artery blood flow.
abstract: The mechanisms of deficient placentation in the first trimester remain poorly understood, although apoptosis, hypoxia, and oxidative stress have been implicated. High uterine artery Doppler resistance indexes (RIs) are predictive of placental complications of pregnancy, such as preeclampsia, fetal growth restriction, and stillbirth. We provide evidence that even in the first trimester, pregnancies with high uterine artery Doppler RI demonstrate alterations in placental gene and protein expression. Apoptosis was significantly higher in high RI placental tissue, as determined by Western blot analysis of cleaved poly (ADP-ribose) polymerase and caspase 3. Protein expression of the trophoblast survival factor insulin-like growth factor-2 was significantly lower. Both high and normal RI placentas showed evidence of hypoxia and oxidative stress with expression of hypoxia-inducible factors 1α and 2α, heat shock protein 70, presence of nitrotyrosine residues, and lipid peroxidation. We observed no exaggerated placental hypoxia or oxidative stress associated with high RI pregnancies. High RI placental tissue demonstrated an altered balance of antioxidant enzyme activity. Hypoxia and oxidative stress appear to be a physiological state in early pregnancy; our data did not support the hypothesis that they are associated with deficient placentation in the first trimester. Higher levels of apoptosis, reduced insulin-like growth factor-2 expression, and altered antioxidant defenses may contribute to abnormal placentation and the later development of pregnancy complications, such as preeclampsia, fetal growth restriction, and stillbirth.
authors.affiliation: Institute of Cardiovascular and Cell Sciences, St. George's University of London, London, United Kingdom; Fetal Medicine Unit, St. George's Hospital, London, United Kingdom.
authors.forename: Karin
authors.initials: K
authors.lastname: Leslie
authors.affiliation: Institute of Cardiovascular and Cell Sciences, St. George's University of London, London, United Kingdom.
authors.forename: Guy StJ
authors.initials: GS
authors.lastname: Whitley
authors.affiliation: Experimental and Clinical Research Center, a Joint Cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Herse
authors.affiliation: Experimental and Clinical Research Center, a Joint Cooperation between the Max-Delbrück Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.affiliation: Institute of Cardiovascular and Cell Sciences, St. George's University of London, London, United Kingdom.
authors.forename: Sandra V
authors.initials: SV
authors.lastname: Ashton
authors.affiliation: Institute of Infection and Immunity, St. George's University of London, London, United Kingdom.
authors.forename: Ken
authors.initials: K
authors.lastname: Laing
authors.affiliation: Fetal Medicine Unit, St. George's Hospital, London, United Kingdom.
authors.forename: Baskaran
authors.initials: B
authors.lastname: Thilaganathan
authors.affiliation: Institute of Cardiovascular and Cell Sciences, St. George's University of London, London, United Kingdom. Electronic address: jcartwri@sgul.ac.uk.
authors.forename: Judith E
authors.initials: JE
authors.lastname: Cartwright
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D006801:Humans; D010100:Oxygen / Q000378:metabolism*; D010920:Placenta / Q000098:blood supply / Q000378:metabolism; D010929:Placentation / Q000502:physiology; D011225:Pre-Eclampsia / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000517:prevention & control; D011261:Pregnancy Trimester, First / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology*; D055988:Uterine Artery / Q000378:metabolism*; D014599:Uterus / Q000098:blood supply*; D055815:Young Adult
chemical_list: D010100:Oxygen