title: Chinese herbal medicine for miscarriage affects decidual micro-environment and fetal growth.
abstract: BACKGROUND
  Intrauterine growth restriction complicates 5-10% of pregnancies. This study aims to test the hypothesis that Chinese herbal formula, JLFC01, affects pregnancy and fetal development by modulating the pro-inflammatory decidual micro-environment.
  
  
  METHODS
  Human decidua from gestational age-matched elective terminations or incomplete/missed abortion was immunostained using anti-CD68 + anti-CD86 or anti-CD163 antibodies. qRT-PCR and Luminex assay measured the effects of JLFC01 on IL-1β- or TNF-α-induced cytokine expression in first trimester decidual cells and on an established spontaneous abortion/intrauterine growth restriction (SA/IUGR)-prone mouse placentae. The effect of JLFC01 on human endometrial endothelial cell angiogenesis was evaluated by average area, length and numbers of branching points of tube formation. Food intake, litter size, fetal weight, placental weight and resorption rate were recorded in SA/IUGR-prone mouse treated with JLFC01. qRT-PCR, Western blot and immunohistochemistry assessed the expression of mouse placental IGF-I and IGF-IR.
  
  
  RESULTS
  In spontaneous abortion, numbers of decidual macrophages expressing CD86 and CD163 are increased and decreased, respectively. JLFC01 reduces IL-1β- or TNF-α-induced GM-CSF, M-CSF, C-C motif ligand 2 (CCL2), interferon-γ-inducible protein-10 (IP-10), CCL5 and IL-8 production in first trimester decidual cells. JLFC01 suppresses the activity of IL-1β- or TNF-α-treated first trimester decidual cells in enhancing macrophage-inhibited angiogenesis. In SA/IUGR-prone mice, JLFC01 increases maternal food intake, litter size, fetal and placental weight, and reduces fetal resorption rate. JLFC01 induces IGF-I and IGF-IR expression and inhibits M-CSF, CCL2, CCL5, CCL11, CCL3 and G-CSF expression in the placentae.
  
  
  CONCLUSIONS
  JLFC01 improves gestation by inhibiting decidual inflammation, enhancing angiogenesis and promoting fetal growth.
authors.affiliation: Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
authors.forename: L
authors.initials: L
authors.lastname: Piao
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan, ROC.
authors.forename: C-P
authors.initials: CP
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: C-C
authors.initials: CC
authors.lastname: Yeh
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: M
authors.initials: M
authors.lastname: Basar
authors.affiliation: Department of Obstetrics and Gynecology, Beth Israel Medical Center, New York, NY 10003, USA.
authors.forename: R
authors.initials: R
authors.lastname: Masch
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Y C
authors.initials: YC
authors.lastname: Cheng
authors.affiliation: College of Medicine, South Florida University, Tampa, FL 33620, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Lockwood
authors.affiliation: College of Medicine, South Florida University, Tampa, FL 33620, USA.
authors.forename: F
authors.initials: F
authors.lastname: Schatz
authors.affiliation: Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210, USA. Electronic address: joseph.huang@osumc.edu.
authors.forename: S J
authors.initials: SJ
authors.lastname: Huang
mesh_terms: D000022:Abortion, Spontaneous / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D060833:Cellular Microenvironment / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005317:Fetal Growth Retardation / Q000517:prevention & control*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D008808:Mice, Inbred CBA; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D013002:Somatomedins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D013002:Somatomedins; D014409:Tumor Necrosis Factor-alpha; C054593:keishibukuryogan
keywords: Chinese herbal medicine; Decidual cells; IUGR; Macrophage; Spontaneous abortion