Zou, Z, Harris, LK, Forbes, K orcid.org/0000-0002-3745-1337 et al. (1 more author) (2022) Placental expression of Estrogen related receptor gamma (ESRRG) is reduced in FGR pregnancies and is mediated by hypoxia. Biology of Reproduction. ISSN 0006-3363
Abstract
Fetal growth restriction (FGR) describes a fetus which has not achieved its genetic growth potential, it is closely linked to placental dysfunction and uteroplacental hypoxia. Estrogen related receptor gamma (ESRRG) is regulated by hypoxia and is highly expressed in the placenta. We hypothesised ESRRG is a regulator of hypoxia-mediated placental dysfunction in FGR pregnancies. Placentas were collected from women delivering appropriate for gestational age (AGA; n = 14) or FGR (n = 14) infants. Placental explants (n = 15) from uncomplicated pregnancies were cultured for up to 4 days in 21% or 1% O2, or with 200 μM cobalt chloride (CoCl2), or treated with the ESRRG agonists DY131 under different oxygen concentrations. RT-PCR, Western blotting and immunochemistry were used to assess mRNA and protein levels of ESRRG and its localization in placental tissue from FGR or AGA pregnancies, and in cultured placental explants. ESRRG mRNA and protein expression were significantly reduced in FGR placentas, as was mRNA expression of the downstream targets of ESRRG, HSD11B2, and CYP19A1.1. HIF-1alpha protein localised to the nuclei of the cytotrophoblasts and stromal cells in the explants exposed to CoCl2 or 1% O2. Both hypoxia and CoCl2 treatment decreased ESRRG and its downstream genes’ mRNA expression, but not ESRRG protein expression. DY131 increased expression of ESRRG signalling pathways and prevented abnormal cell turnover induced by hypoxia. These data demonstrate that placental ESRRG is hypoxia-sensitive and altered ESRRG-mediated signaling may contribute to hypoxia-induced placental dysfunction in FGR. Furthermore, DY131 could be used as a novel therapeutic approach for the treatment of placental dysfunction.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 16 May 2022 07:47 |
Last Modified: | 18 Jul 2022 09:15 |
Status: | Published online |
Publisher: | Oxford University Press |
Identification Number: | 10.1093/biolre/ioac108 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:186782 |