title: Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia.
abstract: BACKGROUND
  Preeclampsia is a maternal hypertensive disorder with uncertain etiology and a leading cause of maternal and fetal mortality worldwide, causing nearly 40% of premature births delivered before 35 weeks of gestation. The first stage of preeclampsia is characterized by reduction of utero-placental blood flow which is reflected in high blood pressure and proteinuria during the second half of pregnancy. In human placenta androgens derived from the maternal and fetal adrenal glands are converted into estrogens by the enzymatic action of placental aromatase. This implies that alterations in placental steroidogenesis and, subsequently, in the functionality or bioavailability of placental aromatase may be mechanistically involved in the pathophysiology of PE.
  
  
  METHODS
  Serum samples were collected at 32-36 weeks of gestation and placenta biopsies were collected at time of delivery from PE patients (n = 16) and pregnant controls (n = 32). The effect of oxygen tension on placental cells was assessed by incubation JEG-3 cells under 1% and 8% O2 for different time periods, Timed-mated, pregnant New Zealand white rabbits (n = 6) were used to establish an in vivo model of placental ischemia (achieved by ligature of uteroplacental vessels). Aromatase content and estrogens and androgens concentrations were measured.
  
  
  RESULTS
  The protein and mRNA content of placental aromatase significantly diminished in placentae obtained from preeclamptic patients compared to controls. Similarly, the circulating concentrations of 17-β-estradiol/testosterone and estrone/androstenedione were reduced in preeclamptic patients vs. controls. These data are consistent with a concomitant decrease in aromatase activity. Aromatase content was reduced in response to low oxygen tension in the choriocarcinoma JEG-3 cell line and in rabbit placentae in response to partial ligation of uterine spiral arteries, suggesting that reduced placental aromatase activity in preeclamptic patients may be associated with chronic placental ischemia and hypoxia later in gestation.
  
  
  CONCLUSIONS
  Placental aromatase expression and functionality are diminished in pregnancies complicated by preeclampsia in comparison with healthy pregnant controls.
authors.affiliation: Department of Obstetrics and Gynecology, Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Perez-Sepulveda
authors.affiliation: Department of Obstetrics and Gynecology, Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Lara J
authors.initials: LJ
authors.lastname: Monteiro
authors.affiliation: Department of Obstetrics and Gynecology, Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Aneta
authors.initials: A
authors.lastname: Dobierzewska
authors.affiliation: Department of Obstetrics and Gynecology, Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Pedro P
authors.initials: PP
authors.lastname: España-Perrot
authors.affiliation: Department of Obstetrics and Gynecology, Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Pía
authors.initials: P
authors.lastname: Venegas-Araneda
authors.affiliation: Department of Obstetrics and Gynecology, Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Alejandra M
authors.initials: AM
authors.lastname: Guzmán-Rojas
authors.affiliation: Department of Obstetrics and Gynecology, Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: María I
authors.initials: MI
authors.lastname: González
authors.affiliation: Department of Obstetrics and Gynecology, Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Macarena
authors.initials: M
authors.lastname: Palominos-Rivera
authors.affiliation: Laboratory of Molecular Physiology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Irarrazabal
authors.affiliation: Department of Obstetrics and Gynecology, Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile; Perinatal Unit, Clínica Dávila, Santiago, Chile.
authors.forename: Horacio
authors.initials: H
authors.lastname: Figueroa-Diesel
authors.affiliation: Department of Obstetrics and Gynecology, Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Manuel
authors.initials: M
authors.lastname: Varas-Godoy
authors.affiliation: Department of Obstetrics and Gynecology, Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile; Perinatal Unit, Clínica Dávila, Santiago, Chile.
authors.forename: Sebastián E
authors.initials: SE
authors.lastname: Illanes
mesh_terms: D000328:Adult; D000728:Androgens / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000172:deficiency* / Q000378:metabolism*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D004970:Estrone / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006801:Humans; D007511:Ischemia / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth / Q000378:metabolism; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013739:Testosterone / Q000378:metabolism
chemical_list: D000728:Androgens; D004967:Estrogens; D012333:RNA, Messenger; D004970:Estrone; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D001141:Aromatase