title: Placental expression of DNA methyltransferase 1 (DNMT1): Gender-specific relation with human placental growth.
abstract: Placental physiology and morphology is critically regulated by DNA methylation. As such, placental global DNA methylation and transcript abundance of placental DNA methyltransferases (DNMT1 and DNMT3A) may relate to placental and fetal growth in human pregnancies. We aimed to test correlations of human fetoplacental parameters and birth weight with the placental expression of DNA methyltransferases (DNMT1 and DNMT3A) and placental global methylation.
  
  
  
  Placentae (n = 109) were collected from small- (SGA) and appropriate- (AGA) for gestational age full-term singleton pregnancies (n = 56 SGA and 53 AGA). Placentae and neonates were weighed at birth. Realtime quantitative PCR was performed to assess placental transcript abundance of DNMT1, DNMT3A and DNTMT3B normalized to a panel of reference genes. LINE-1 methylation was measured using a quantitative MethyLight assay in a subset of samples (n = 68). Associations of placental transcript abundances of DNMT1, DNMT3A and DNMT3B and of LINE-1 methylation levels with maternal, placental and neonatal parameters were tested.
  
  
  
  Placental DNMT1 transcript abundance associated positively with placental weight (β = 10.21, P = 0.013). This association was specific to the AGA births (β = 12.77, P = 0.022) and was absent in the SGA births. Association of DNMT1 expression with placental weight and birth weight within the AGA births was specific to the female gender (Birth weight: β = 83.61, P = 0.043; Placental weight: β = 23.92, P = 0.025). Placental DNMT1 transcript levels were not different according to SGA status or gender. Placental DNMT3A transcript levels and LINE-1 methylation levels did not show any associations with maternal, placental and neonatal parameters.
  
  
  
  Placental DNMT1 expression was found to be associated positively with placental weight and birth weight, specifically in the female AGA births. Thus, we hypothesize that placental DNMT1 participates in fetoplacental growth in a fetal gender-specific manner.
authors.affiliation: Division of Nutrition, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India. Electronic address: arpitam@sjri.res.in.
authors.forename: A
authors.initials: A
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Pathology, St John's Medical College, St. John's National Academy of Health Sciences, Bangalore, India.
authors.forename: G
authors.initials: G
authors.lastname: Ravikumar
authors.affiliation: Division of Nutrition, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India.
authors.forename: H
authors.initials: H
authors.lastname: Meraaj
authors.affiliation: Division of Nutrition, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India.
authors.forename: P
authors.initials: P
authors.lastname: Dwarkanath
authors.affiliation: Department of Obstetrics and Gynecology, St John's Medical College, St. John's National Academy of Health Sciences, Bangalore, India.
authors.forename: A
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Department of Pathology, St John's Medical College, St. John's National Academy of Health Sciences, Bangalore, India.
authors.forename: J
authors.initials: J
authors.lastname: Crasta
authors.affiliation: Division of Epidemiology and Biostatistics, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India.
authors.forename: T
authors.initials: T
authors.lastname: Thomas
authors.affiliation: Division of Nutrition, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India.
authors.forename: A V
authors.initials: AV
authors.lastname: Kurpad
authors.affiliation: Division of Molecular Medicine, St. John's Research Institute, St. John's National Academy of Health Sciences, Bangalore, India.
authors.forename: T S
authors.initials: TS
authors.lastname: Sridhar
mesh_terms: D000293:Adolescent; D000328:Adult; D001724:Birth Weight / Q000502:physiology*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1 / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D047109:Fetal Development / Q000502:physiology; D005865:Gestational Age; D006801:Humans; D007236:Infant, Small for Gestational Age / Q000378:metabolism; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; C000619380:DNMT1 protein, human
keywords: DNA methylation; DNMT1; Fetal growth restriction; Gender; Human placenta; SGA