PMID- 30955704
OWN - NLM
STAT- MEDLINE
DCOM- 20200501
LR  - 20231011
IS  - 1532-3102 (Electronic)
IS  - 0143-4004 (Print)
IS  - 0143-4004 (Linking)
VI  - 78
DP  - 2019 Mar
TI  - Sex modifies placental gene expression in response to metabolic and inflammatory 
      stress.
PG  - 1-9
LID - S0143-4004(19)30040-2 [pii]
LID - 10.1016/j.placenta.2019.02.008 [doi]
AB  - INTRODUCTION: Metabolic stress (e.g., gestational diabetes mellitus (GDM) and 
      obesity) and infections are common during pregnancy, impacting fetal development 
      and the health of offspring. Such antenatal stresses can differentially impact 
      male and female offspring. We sought to determine how metabolic stress and 
      maternal immune activation (MIA), either alone or in combination, alters 
      inflammatory gene expression within the placenta and whether the effects 
      exhibited sexual dimorphism. METHODS: Female C57BL/6 J mice were fed a normal 
      diet or a high fat diet for 6 weeks prior to mating, with the latter diet 
      inducing a GDM phenotype during pregnancy. Dams within each diet group at 
      gestational day (GD) 12.5 received either an intraperitoneal injection of the 
      viral mimic, polyinosinic:polycytidylic acid (poly(I:C)) or saline. Three hours 
      post injection; placentae were collected and analyzed for changes in the 
      expression of 248 unique immune genes. RESULTS: Placental immune gene expression 
      was significantly altered by GDM, MIA and the combination of the two (GDM+MIA). 
      mRNA expression was generally lower in placentae of mice exposed to GDM alone 
      compared with the other experimental groups, while mice exposed to MIA exhibited 
      the highest transcript levels. Notably, fetal/placental sex influenced the 
      responses of many immune genes to both metabolic and inflammatory stress. 
      DISCUSSION: GDM and MIA provoke inflammatory responses within the placenta and 
      such effects exhibit sexual dimorphism. The combination of these stressors 
      impacts the placenta differently than either condition alone. These findings may 
      help explain sexual dimorphism observed in adverse pregnancy outcomes in human 
      offspring exposed to similar stressors.
CI  - Copyright (c) 2019. Published by Elsevier Ltd.
FAU - Barke, Theresa L
AU  - Barke TL
AD  - Graduate Program in Microbiology and Immunology, Department of Medicine, 
      Vanderbilt University Medical Center, Nashville, TN, 37232, USA; Division of 
      Infectious Diseases, Department of Medicine, Vanderbilt University Medical 
      Center, Nashville, TN, 37232, USA.
FAU - Money, Kelli M
AU  - Money KM
AD  - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 
      37232, USA.
FAU - Du, Liping
AU  - Du L
AD  - Center for Quantitative Sciences, Department of Biostatistics, Vanderbilt 
      University Medical Center, Nashville, TN, 37232, USA.
FAU - Serezani, Ana
AU  - Serezani A
AD  - Division of Allergy, Pulmonary, and Critical Care Medicine, Department of 
      Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
FAU - Gannon, Maureen
AU  - Gannon M
AD  - Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, 
      Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
FAU - Mirnics, Karoly
AU  - Mirnics K
AD  - Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska 
      Medical Center, Omaha, NE, 68198, USA.
FAU - Aronoff, David M
AU  - Aronoff DM
AD  - Division of Infectious Diseases, Department of Medicine, Vanderbilt University 
      Medical Center, Nashville, TN, 37232, USA; Department of Pathology, Microbiology 
      and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA; 
      Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, 
      Nashville, TN, 37232, USA. Electronic address: d.aronoff@vanderbilt.edu.
LA  - eng
GR  - T32 MH064913/MH/NIMH NIH HHS/United States
GR  - F31 DK108652/DK/NIDDK NIH HHS/United States
GR  - R01 MH110636/MH/NIMH NIH HHS/United States
GR  - R01 MH079299/MH/NIMH NIH HHS/United States
GR  - R24 DK090964/DK/NIDDK NIH HHS/United States
GR  - T32 GM007347/GM/NIGMS NIH HHS/United States
GR  - P30 DK020593/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190222
PL  - Netherlands
TA  - Placenta
JT  - Placenta
JID - 8006349
SB  - IM
MH  - Animals
MH  - Diabetes, Gestational/genetics/metabolism/pathology
MH  - Diet, High-Fat
MH  - Female
MH  - Fetal Development
MH  - Fetus/*physiology
MH  - Gene Expression
MH  - Inflammation/*genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Obesity/genetics/metabolism
MH  - Placenta/*metabolism
MH  - Pregnancy
MH  - Pregnancy Complications/genetics/metabolism
MH  - *Sex Characteristics
MH  - Stress, Physiological/*genetics
MH  - Transcriptome
PMC - PMC6461364
MID - NIHMS1522859
OTO - NOTNLM
OT  - Diabetes
OT  - Fetal origins
OT  - Immunology
OT  - Infection
OT  - Maternal-child health
EDAT- 2019/04/09 06:00
MHDA- 2020/05/02 06:00
PMCR- 2020/03/01
CRDT- 2019/04/09 06:00
PHST- 2018/11/28 00:00 [received]
PHST- 2019/01/25 00:00 [revised]
PHST- 2019/02/18 00:00 [accepted]
PHST- 2019/04/09 06:00 [entrez]
PHST- 2019/04/09 06:00 [pubmed]
PHST- 2020/05/02 06:00 [medline]
PHST- 2020/03/01 00:00 [pmc-release]
AID - S0143-4004(19)30040-2 [pii]
AID - 10.1016/j.placenta.2019.02.008 [doi]
PST - ppublish
SO  - Placenta. 2019 Mar;78:1-9. doi: 10.1016/j.placenta.2019.02.008. Epub 2019 Feb 22.