PMID- 30718791
OWN - NLM
STAT- MEDLINE
DCOM- 20200828
LR  - 20200828
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Feb 4
TI  - The Placental Transcriptome in Late Gestational Hypoxia Resulting in Murine 
      Intrauterine Growth Restriction Parallels Increased Risk of Adult Cardiometabolic 
      Disease.
PG  - 1243
LID - 10.1038/s41598-018-37627-y [doi]
LID - 1243
AB  - Intrauterine growth restriction (IUGR) enhances risk for adult onset 
      cardiovascular disease (CVD). The mechanisms underlying IUGR are poorly 
      understood, though inadequate blood flow and oxygen/nutrient provision are 
      considered common endpoints. Based on evidence in humans linking IUGR to adult 
      CVD, we hypothesized that in murine pregnancy, maternal late gestational hypoxia 
      (LG-H) exposure resulting in IUGR would result in (1) placental transcriptome 
      changes linked to risk for later CVD, and 2) adult phenotypes of CVD in the IUGR 
      offspring. After subjecting pregnant mice to hypoxia (10.5% oxygen) from 
      gestational day (GD) 14.5 to 18.5, we undertook RNA sequencing from GD19 
      placentas. Functional analysis suggested multiple changes in structural and 
      functional genes important for placental health and function, with maximal 
      dysregulation involving vascular and nutrient transport pathways. Concordantly, a 
      ~10% decrease in birthweights and ~30% decrease in litter size was observed, 
      supportive of placental insufficiency. We also found that the LG-H IUGR offspring 
      exhibit increased risk for CVD at 4 months of age, manifesting as hypertension, 
      increased abdominal fat, elevated leptin and total cholesterol concentrations. In 
      summary, this animal model of IUGR links the placental transcriptional response 
      to the stressor of gestational hypoxia to increased risk of developing 
      cardiometabolic disease.
FAU - Chu, Alison
AU  - Chu A
AD  - David Geffen School of Medicine at UCLA, Department of Pediatrics, Division of 
      Neonatology & Developmental Biology, Neonatal Research Center of the UCLA 
      Children's Discovery and Innovation Institute, 10833 Le Conte Avenue, MDCC 
      B2-375, Los Angeles, CA, 90095, USA. alisonchu@mednet.ucla.edu.
FAU - Casero, David
AU  - Casero D
AD  - David Geffen School of Medicine at UCLA, Department of Pathology and Laboratory 
      Medicine, 3000 Terasaki Life Sciences Building, 610 Charles Young Drive East, Los 
      Angeles, CA, 90095, USA. dcasero@ucla.edu.
FAU - Thamotharan, Shanthie
AU  - Thamotharan S
AD  - David Geffen School of Medicine at UCLA, Department of Pediatrics, Division of 
      Neonatology & Developmental Biology, Neonatal Research Center of the UCLA 
      Children's Discovery and Innovation Institute, 10833 Le Conte Avenue, MDCC 
      B2-375, Los Angeles, CA, 90095, USA.
FAU - Wadehra, Madhuri
AU  - Wadehra M
AD  - David Geffen School of Medicine at UCLA, Department of Pathology and Laboratory 
      Medicine, 4525 MacDonald Research Laboratories, Los Angeles, CA, 90095, USA.
FAU - Cosi, Amy
AU  - Cosi A
AD  - David Geffen School of Medicine at UCLA, Department of Pediatrics, Division of 
      Neonatology & Developmental Biology, Neonatal Research Center of the UCLA 
      Children's Discovery and Innovation Institute, 10833 Le Conte Avenue, MDCC 
      B2-375, Los Angeles, CA, 90095, USA.
FAU - Devaskar, Sherin U
AU  - Devaskar SU
AD  - David Geffen School of Medicine at UCLA, Department of Pediatrics, Division of 
      Neonatology & Developmental Biology, Neonatal Research Center of the UCLA 
      Children's Discovery and Innovation Institute, 10833 Le Conte Avenue, MDCC 
      B2-375, Los Angeles, CA, 90095, USA.
LA  - eng
GR  - R01 HD041230/HD/NICHD NIH HHS/United States
GR  - 1K08HD093874-01/U.S. Department of Health & Human Services | NIH | Eunice 
      Kennedy Shriver National Institute of Child Health and Human Development 
      (NICHD)/International
GR  - R01 HD081206/HD/NICHD NIH HHS/United States
GR  - KL2 TR001882/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190204
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Cardiovascular Diseases/*genetics
MH  - Disease Models, Animal
MH  - Female
MH  - Fetal Growth Retardation/*genetics
MH  - *Gene Expression Regulation, Developmental
MH  - Humans
MH  - Hypoxia/*complications
MH  - Infant, Newborn
MH  - Male
MH  - Maternal-Fetal Exchange/genetics
MH  - Mice
MH  - Nutrients/metabolism
MH  - Oxygen/metabolism
MH  - Placenta/metabolism/pathology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*genetics
MH  - RNA-Seq
MH  - Transcriptome
PMC - PMC6361888
COIS- The authors declare no competing interests.
EDAT- 2019/02/06 06:00
MHDA- 2020/08/29 06:00
PMCR- 2019/02/04
CRDT- 2019/02/06 06:00
PHST- 2018/06/15 00:00 [received]
PHST- 2018/12/11 00:00 [accepted]
PHST- 2019/02/06 06:00 [entrez]
PHST- 2019/02/06 06:00 [pubmed]
PHST- 2020/08/29 06:00 [medline]
PHST- 2019/02/04 00:00 [pmc-release]
AID - 10.1038/s41598-018-37627-y [pii]
AID - 37627 [pii]
AID - 10.1038/s41598-018-37627-y [doi]
PST - epublish
SO  - Sci Rep. 2019 Feb 4;9(1):1243. doi: 10.1038/s41598-018-37627-y.