title: Potential reproductive toxicity of Largehead Atractylodes Rhizome, the most commonly used Chinese medicine for threatened miscarriage.
abstract: BACKGROUND
  Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese medicine to prevent early pregnancy loss due to threatened miscarriage. However, its safety profile during pregnancy is still not available. Here we aimed to identify the potential adverse effects of LAR on embryo-fetal development as well as prenatal and post-natal growth.
  
  
  METHODS
  Pregnant mice, rats and rabbits were orally administered with LAR extracts in various doses (from 1×, 2×, 3× and up to 6× clinical doses) at different gestational periods (implantation, gastrulation, organogenesis, maturation and whole gestation). Maternal effects on weight loss, implantation failure and fetal resorption and perinatal effects on developmental delay, growth restriction and congenital malformations were studied.
  
  
  RESULTS
  In mice, with early LAR exposure, a significant decrease in fetal growth parameters and a significant increase in post-implantation loss were identified. With late LAR exposure, significant increases in gestational duration as well as prenatal and post-natal mortality were found. At high clinical doses, congenital skeletal malformations were recorded. In rabbits, fetal resorption, hydrops fetalis and short ear anomaly were observed. No significant adverse effects were found in rats.
  
  
  CONCLUSIONS
  Potential reproductive toxicity of LAR in pregnant animals was identified within the clinical dose. Caution should be taken in clinical applications of LAR during pregnancy.
authors: Department of Obstetrics and Gynaecology,  The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories,  Hong Kong.
authors: L
authors: L
authors: Li
authors: L Y
authors: LY
authors: Tang
authors: Gene C W
authors: GC
authors: Man
authors: Benson H Y
authors: BH
authors: Yeung
authors: Clara B S
authors: CB
authors: Lau
authors: P C
authors: PC
authors: Leung
authors: C C
authors: CC
authors: Wang
mesh_terms: D000014:Abnormalities, Drug-Induced; D000028:Abortion, Induced; D000033:Abortion, Threatened / Q000188:drug therapy*; D000818:Animals; D031174:Atractylodes / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000633:toxicity*; D004423:Ear / Q000002:abnormalities; D010064:Embryo Implantation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced; D005327:Fetal Resorption / Q000139:chemically induced; D015160:Hydrops Fetalis / Q000139:chemically induced; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019055:No-Observed-Adverse-Effect Level; D008517:Phytotherapy / Q000009:adverse effects*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D027343:Rhizome; D012886:Skull / Q000002:abnormalities
chemical_list: D004365:Drugs, Chinese Herbal