title: Placental STAT3 signaling is activated in women with polycystic ovary syndrome.
abstract: OBJECTIVE
  Does polycystic ovary syndrome (PCOS) in women without pregnancy complications affect placental signal transducer and activator of transcription 3 (STAT3) and mechanistic target of rapamycin (mTOR) signaling?
  
  
  CONCLUSIONS
  Placental STAT3 signaling is activated but mTOR signaling is unaffected in PCOS.
  
  
  BACKGROUND
  Women with PCOS have increased risk of poor pregnancy outcomes (e.g. restricted or accelerated fetal growth), indicating placental dysfunction. Placental STAT3 and mTOR pathways regulate placental function and indirectly affect fetal growth.
  
  
  METHODS
  In a case-control study, placental tissue and maternal blood were collected at delivery from 40 control pregnant women and 38 PCOS women with uncomplicated pregnancy.
  
  
  METHODS
  Women with PCOS were recruited at two medical centers and pregnant controls were recruited at one of these centers. Placental mRNA expression of genes encoding proteins related to steroid action, metabolic pathways and cytokines was analyzed by quantitative RT-PCR. Phosphorylated placental STAT3 (P-STAT3) and mTOR targets was measured by western blot. Levels of sex steroids in serum were determined by mass spectrometry.
  
  
  RESULTS
  Placental P-STAT3 (Tyr-705) was increased in women with PCOS (P < 0.05) versus controls. Placental mTOR signaling was not affected in PCOS women when compared with controls. Circulating levels of androstenedione, androst-5-ene-3β, 17β-diol, testosterone, 5α-dihydrotestosterone and etiocholanolone glucuronide were higher and estradiol lower in women with PCOS than in controls (all P < 0.05). No correlation between sex steroid levels in serum and P-STAT3 was observed.
  
  
  CONCLUSIONS
  Women with PCOS and pregnancy complications were excluded to avoid the confounding effects of placental pathologies, which could modify STAT3 and mTOR signaling. Moreover, 97.4% of women with PCOS in the study displayed oligoamenorrhea at diagnosis. Thus, the current findings could be restricted to PCOS women with the oligo-anovulatory phenotype without pregnancy complications.
  
  
  CONCLUSIONS
  Phosphorylation of STAT3 is increased in the placenta from women with PCOS and uncomplicated pregnancies, indicating that specific metabolic placental pathways are activated in the absence of obstetric and perinatal complications.
  
  
  BACKGROUND
  The work was supported by the Swedish Medical Research Council (Project No. 2011-2732 and 2014-2775); Jane and Dan Olsson Foundation, Wilhelm and Martina Lundgrens's Science Fund; Hjalmar Svensson Foundation (E.S.-V and M.M.); Adlerbert Research Foundation; Swedish federal government under the LUA/ALF agreement ALFFGBG-136481 and 429501 and the Regional Research and Development agreement (VGFOUREG-5171, -11296 and -7861). MM thanks the Becas Chile Programme (Chile) and University of Chile for financial support through a postdoctoral fellowship. There are no competing interests.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Laboratorio de Endocrinología y Metabolismo, Departamento de Medicina Occidente, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: M
authors.initials: M
authors.lastname: Maliqueo
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Sundström Poromaa
authors.affiliation: Institute of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Vanky
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Fornes
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Benrick
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Åkerud
authors.affiliation: Institute of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Stridsklev
authors.affiliation: EndoCeutics, Quebec City, Quebec, Canada G1V 4M7.
authors.forename: F
authors.initials: F
authors.lastname: Labrie
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado, Aurora, CO, USA.
authors.forename: T
authors.initials: T
authors.lastname: Jansson
authors.affiliation: Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Department of Physiology and Pharmacology, Karolinska Institutet, Von Eulersväg 4, SE-171 77 Stockholm, Sweden elisabet.stener-victorin@ki.se.
authors.forename: E
authors.initials: E
authors.lastname: Stener-Victorin
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D010766:Phosphorylation; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D011247:Pregnancy; D011256:Pregnancy Outcome; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: hyperandrogenemia; mechanistic target of rapamycin; polycystic ovary syndrome; pregnancy; signal transducer and activator of transcription 3