title: Maternal testosterone and placental function: Effect of electroacupuncture on placental expression of angiogenic markers and fetal growth.
abstract: Women with polycystic ovary syndrome (PCOS) have elevated circulating androgens during pregnancy and are at an increased risk of adverse pregnancy outcomes. Here we tested the hypotheses that maternal androgen excess decrease placental and fetal growth, and placental expression of markers of steroidogenesis, angiogenesis and sympathetic activity, and that acupuncture with low-frequency electrical stimulation prevents these changes. Pregnant rats were exposed to vehicle or testosterone on gestational day (GD)15-19. Low-frequency electroacupuncture (EA) or handling, as a control for the EA procedure, was given to control or testosterone exposed dams on GD16-20. On GD21, blood pressure was measured and maternal blood, fetuses and placentas collected. Placental steroid receptor expression and proteins involved in angiogenic, neurotrophic and adrenergic signaling were analyzed. EA did not affect any variables in control rats except maternal serum corticosterone, which was reduced. EA in testosterone exposed dams compared with controls increased systolic pressure by 30%, decreased circulating norepinephrine and corticosterone, fetal and placental weight and placental VEGFR1 and proNGF protein expression, and increased the VEGFA/VEGFR1 ratio, mature NGF (mNGF) and the mNGF/proNGF ratio. In conclusion, low-frequency EA in control animals did not have any negative influence on any of the studied variables. In contrast, EA in pregnant dams exposed to testosterone increased blood pressure and impaired placental growth and function, leading to decreased fetal growth.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Romina
authors.initials: R
authors.lastname: Fornes
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Endocrinology and Metabolism Laboratory, Department of Medicine, West division, University of Chile, Santiago, Chile.
authors.forename: Manuel
authors.initials: M
authors.lastname: Maliqueo
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Milana
authors.initials: M
authors.lastname: Kokosar
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Benrick
authors.affiliation: Department of Maternal and Fetal Medicine, UCL Institute for Women's Health, University College London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Carr
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Billig
authors.affiliation: Department of Obstetrics & Gynecology, Division of Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jansson
authors.affiliation: Institute of Translational Pharmacology - CNR, via del Fosso del Cavaliere 100, 00133 Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Manni
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden. Electronic address: elisabet.stener-victorin@ki.se.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Stener-Victorin
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism; D015671:Electroacupuncture / Q000009:adverse effects*; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D005333:Fetus / Q000378:metabolism / Q000502:physiology; D010920:Placenta / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D013739:Testosterone; D003345:Corticosterone
keywords: Acupuncture; Electrical stimulation; Fetus; Maternal androgen excess; Placenta; Polycystic ovary syndrome