PMID- 25833255
OWN - NLM
STAT- MEDLINE
DCOM- 20160606
LR  - 20230411
IS  - 1476-5497 (Electronic)
IS  - 0307-0565 (Print)
IS  - 0307-0565 (Linking)
VI  - 39
IP  - 8
DP  - 2015 Aug
TI  - Sexual dimorphism in miR-210 expression and mitochondrial dysfunction in the 
      placenta with maternal obesity.
PG  - 1274-81
LID - 10.1038/ijo.2015.45 [doi]
AB  - BACKGROUND: Maternal obesity is a major problem in obstetrics, and the placenta 
      is involved in obesity-related complications via its roles at the maternal-fetal 
      interface. We have recently shown a causative role for micro(mi)RNA-210, a so 
      called 'hypoxamir' regulated by HIF-1alpha, in mitochondrial dysfunction in placentas 
      from women with preeclampsia. We also reported mitochondrial dysfunction in 
      placentas with maternal obesity. Here we hypothesized that expression of miR-210 
      is dysregulated in the placentas with obesity. METHODS: Placentas from 
      uncomplicated pregnancies were collected at term from healthy weight or control 
      (CTRL, pre-pregnancy body mass index (BMI)<25), overweight (OW, BMI=25-24.9) and 
      obese (OB, BMI>30) women following C-section with no labor. Expression of 
      miRNA-210 and its target genes was measured by reverse transcription-PCR and 
      Western Blot, respectively. Mitochondrial respiration was assessed by Seahorse 
      Analyzer in syncytiotrophoblast (ST) 72 h after cytotrophoblast isolation. 
      RESULTS: Expression of miR-210 was significantly increased in placentas of OB and 
      OW women with female but not male fetuses compared with CTRL placentas of 
      females. However, expression of HIF-1alpha in these placentas remained unchanged. 
      Levels of tumor-necrosis factor-alpha (TNFalpha) were increased in OW and OB 
      placentas of females but not males, and in silico analysis suggested that 
      activation of miR-210 expression in these placentas might be activated by NFkappaB1 
      (p50) signaling. Indeed, chromatin Immunoprecipitation assay showed that NFkB1 
      binds to placental miR-210 promoter in a fetal sex-dependent manner. Female but 
      not male STs treated with TNFalpha showed overexpression of miR-210, reduction of 
      mitochondrial target genes and decreased mitochondrial respiration. Pre-treatment 
      of these STs with small interfering RNA to NFkB1 or antagomiR-210 prevented the 
      TNFalpha-mediated inhibition of mitochondrial respiration. CONCLUSIONS: Our data 
      suggest that the inflammatory intrauterine environment associated with maternal 
      obesity induces an NFkappaB1-mediated increase in miR-210 in a fetal sex-dependent 
      manner, leading to inhibition of mitochondrial respiration and placental 
      dysfunction in the placentas of female fetuses.
FAU - Muralimanoharan, S
AU  - Muralimanoharan S
AD  - Center for Pregnancy and Newborn Research, Department of Obstetrics and 
      Gynecology, University of Texas Health Science Center, San Antonio, TX, USA.
FAU - Guo, C
AU  - Guo C
AD  - Center for Pregnancy and Newborn Research, Department of Obstetrics and 
      Gynecology, University of Texas Health Science Center, San Antonio, TX, USA.
FAU - Myatt, L
AU  - Myatt L
AD  - Center for Pregnancy and Newborn Research, Department of Obstetrics and 
      Gynecology, University of Texas Health Science Center, San Antonio, TX, USA.
FAU - Maloyan, A
AU  - Maloyan A
AD  - Center for Pregnancy and Newborn Research, Department of Obstetrics and 
      Gynecology, University of Texas Health Science Center, San Antonio, TX, USA.
LA  - eng
GR  - HD076259A/HD/NICHD NIH HHS/United States
GR  - UL1 RR025767/RR/NCRR NIH HHS/United States
GR  - KL2 TR001118/TR/NCATS NIH HHS/United States
GR  - R01 HD076259/HD/NICHD NIH HHS/United States
GR  - R01 HL075297/HL/NHLBI NIH HHS/United States
GR  - UL1RR025767/RR/NCRR NIH HHS/United States
GR  - HL075297/HL/NHLBI NIH HHS/United States
GR  - UL1 TR001120/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 - 20150402
PL  - England
TA  - Int J Obes (Lond)
JT  - International journal of obesity (2005)
JID - 101256108
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (MIRN210 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Adult
MH  - Blotting, Western
MH  - Cell Hypoxia
MH  - Female
MH  - Fetal Development
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Immunity, Innate
MH  - Inflammation/immunology/*metabolism
MH  - MicroRNAs/*metabolism
MH  - Mitochondria
MH  - NF-kappa B/metabolism
MH  - Obesity/complications/*metabolism/physiopathology
MH  - Placenta/immunology/*metabolism
MH  - Pregnancy
MH  - Pregnancy Complications/*metabolism/physiopathology
MH  - Pregnant Women
MH  - Protein Transport
MH  - Sex Characteristics
MH  - Term Birth
PMC - PMC4526386
MID - NIHMS708235
COIS- CONFLICT OF INTEREST The authors declare no conflict of interest.
EDAT- 2015/04/03 06:00
MHDA- 2016/06/09 06:00
PMCR- 2015/08/05
CRDT- 2015/04/03 06:00
PHST- 2014/10/31 00:00 [received]
PHST- 2015/01/30 00:00 [revised]
PHST- 2015/02/08 00:00 [accepted]
PHST- 2015/04/03 06:00 [entrez]
PHST- 2015/04/03 06:00 [pubmed]
PHST- 2016/06/09 06:00 [medline]
PHST- 2015/08/05 00:00 [pmc-release]
AID - ijo201545 [pii]
AID - 10.1038/ijo.2015.45 [doi]
PST - ppublish
SO  - Int J Obes (Lond). 2015 Aug;39(8):1274-81. doi: 10.1038/ijo.2015.45. Epub 2015 
      Apr 2.