PMID- 31436841
OWN - NLM
STAT- MEDLINE
DCOM- 20191223
LR  - 20210111
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 160
IP  - 11
DP  - 2019 Nov 1
TI  - Prenatal Testosterone Excess Disrupts Placental Function in a Sheep Model of 
      Polycystic Ovary Syndrome.
PG  - 2663-2672
LID - 10.1210/en.2019-00386 [doi]
AB  - Polycystic ovary syndrome (PCOS) is a common condition of reproductive-aged 
      women. In a well-validated sheep model of PCOS, testosterone (T) treatment of 
      pregnant ewes culminated in placental insufficiency and intrauterine growth 
      restriction of offspring. The purpose of this study was to explore specific 
      mechanisms by which T excess compromises placental function in early, mid, and 
      late gestation. Pregnant Suffolk sheep received T propionate 100 mg 
      intramuscularly or control vehicle twice weekly from gestational days (GD) 30 to 
      90 (term = 147 days). Placental harvest occurred at GD 65, 90, and 140. Real-time 
      RT-PCR was used to assess transcript levels of proinflammatory (TNF, IL1B, IL6, 
      IL8, monocyte chemoattractant protein-1/chemokine ligand 2, cluster of 
      differentiation 68), antioxidant (glutathione reductase and superoxide dismutase 
      1 and 2), and angiogenic [vascular endothelial growth factor (VEGF) and 
      hypoxia-inducible factor 1alpha (HIF1A)] genes. Lipid accumulation was assessed using 
      triglyceride assays and Oil Red O staining. Placental measures of oxidative and 
      nitrative stress included the thiobarbituric acid reactive substance assay and 
      high-pressure liquid chromatography. Tissue fibrosis was assessed with 
      Picrosirius Red staining. Student t tests and Cohen effect-size analyses were 
      used for statistical analysis. At GD 65, T-treated placentomes showed increased 
      lipid accumulation and collagen deposition. Notable findings at GD 90 were a 
      significant increase in HIF1A expression and a large effect increase in VEGF 
      expression. At GD 140, T-treated placentomes displayed large effect increases in 
      expression of hypoxia and inflammatory markers. In summary, T treatment during 
      early pregnancy induces distinct gestational age-specific effects on the 
      placental milieu, which may underlie the previously observed phenotype of 
      placental insufficiency.
CI  - Copyright (c) 2019 Endocrine Society.
FAU - Kelley, Angela S
AU  - Kelley AS
AD  - Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, 
      Michigan.
FAU - Puttabyatappa, Muraly
AU  - Puttabyatappa M
AD  - Department of Pediatrics, University of Michigan, Ann Arbor, Michigan.
FAU - Ciarelli, Joseph N
AU  - Ciarelli JN
AD  - Department of Pediatrics, University of Michigan, Ann Arbor, Michigan.
FAU - Zeng, Lixia
AU  - Zeng L
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
FAU - Smith, Yolanda R
AU  - Smith YR
AD  - Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, 
      Michigan.
FAU - Lieberman, Richard
AU  - Lieberman R
AD  - Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, 
      Michigan.
AD  - Department of Pathology, University of Michigan, Ann Arbor, Michigan.
FAU - Pennathur, Subramaniam
AU  - Pennathur S
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
FAU - Padmanabhan, Vasantha
AU  - Padmanabhan V
AD  - Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, 
      Michigan.
AD  - Department of Pediatrics, University of Michigan, Ann Arbor, Michigan.
LA  - eng
GR  - P01 HD044232/HD/NICHD NIH HHS/United States
GR  - P30 DK020572/DK/NIDDK NIH HHS/United States
GR  - P30 DK089503/DK/NIDDK NIH HHS/United States
GR  - P30 DK092926/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 3XMK78S47O (Testosterone)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Female
MH  - Placenta/metabolism/*physiopathology
MH  - Polycystic Ovary Syndrome/metabolism/*physiopathology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Sheep
MH  - Testosterone
PMC - PMC6804485
EDAT- 2019/08/23 06:00
MHDA- 2019/12/24 06:00
PMCR- 2020/08/22
CRDT- 2019/08/23 06:00
PHST- 2019/05/20 00:00 [received]
PHST- 2019/08/15 00:00 [accepted]
PHST- 2019/08/23 06:00 [pubmed]
PHST- 2019/12/24 06:00 [medline]
PHST- 2019/08/23 06:00 [entrez]
PHST- 2020/08/22 00:00 [pmc-release]
AID - 5552703 [pii]
AID - 201900386 [pii]
AID - 10.1210/en.2019-00386 [doi]
PST - ppublish
SO  - Endocrinology. 2019 Nov 1;160(11):2663-2672. doi: 10.1210/en.2019-00386.