title: Human placental transcriptome shows sexually dimorphic gene expression and responsiveness to maternal dietary n-3 long-chain polyunsaturated fatty acid intervention during pregnancy.
abstract: BACKGROUND
  Previously we have examined the effect of maternal dietary n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy on offspring fat mass. Considering the involvement of the placenta in fetal programming, we aimed to analyze the sex-specific gene expression in human term placenta and its response to the n-3 LCPUFA intervention, as well as their correlations to offspring adiposity.
  
  
  RESULTS
  Placental gene expression was assessed in a control and n-3 LCPUFA intervention group by DNA microarrays, biological pathway analyses and RT-qPCR validation. Expression data were correlated with sex steroid hormone levels in placenta and cord plasma, and offspring anthropometric data. Transcriptome data revealed sexually dimorphic gene expression in control placentas per se, whereas in intervention placentas sex-specific expression changed, and more n-3 LCPUFA-regulated genes were found in female than male placentas. Sexually dimorphic gene expression and n-3 LCPUFA-responsive genes were enriched in the pathway for cell cycle and its associated modulator pathways. Significant mRNA expression changes for CDK6, PCNA, and TGFB1 were confirmed by RT-qPCR. CDK6 and PCNA mRNA levels correlated with offspring birth weight and birth weight percentiles. Significantly reduced placental estradiol-17β/testosterone ratio upon intervention found in female offspring correlated with mRNA levels for the 'Wnt signaling' genes DVL1 and LRP6.
  
  
  CONCLUSIONS
  Overall, human placentas show sexually dimorphic gene expression and responsiveness to maternal n-3 LCPUFA intervention during pregnancy with more pronounced effects in female placentas. The absence of correlations of analyzed placental gene expression with offspring adipose tissue growth in the first year is not mutually exclusive with programming effects, which may manifest later in life, or in other physiological processes.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Sedlmeier
authors.forename: Stefanie
authors.initials: S
authors.lastname: Brunner
authors.forename: Daniela
authors.initials: D
authors.lastname: Much
authors.forename: Philipp
authors.initials: P
authors.lastname: Pagel
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Ulbrich
authors.forename: Heinrich Hd
authors.initials: HH
authors.lastname: Meyer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Amann-Gassner
authors.forename: Hans
authors.initials: H
authors.lastname: Hauner
authors.affiliation: ZIEL-PhD Graduate School 'Epigenetics, Imprinting and Nutrition', Research Center for Nutrition and Food Sciences (ZIEL), Technische Universität München, Freising-Weihenstephan, Germany. bernhard.bader@tum.de.
authors.forename: Bernhard L
authors.initials: BL
authors.lastname: Bader
mesh_terms: D001724:Birth Weight; D002453:Cell Cycle; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D012727:Sex Characteristics; D060449:Wnt Signaling Pathway
chemical_list: D015525:Fatty Acids, Omega-3; D012739:Gonadal Steroid Hormones