Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation

The Journal of Clinical Investigation
María Emilia SolanoPetra Clara Arck

Abstract

Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies in Western societies. IUGR is a strong predictor of reduced short-term neonatal survival and impairs long-term health in children. Placental insufficiency is often associated with IUGR; however, the molecular mechanisms involved in the pathogenesis of placental insufficiency and IUGR are largely unknown. Here, we developed a mouse model of fetal-growth restriction and placental insufficiency that is induced by a midgestational stress challenge. Compared with control animals, pregnant dams subjected to gestational stress exhibited reduced progesterone levels and placental heme oxygenase 1 (Hmox1) expression and increased methylation at distinct regions of the placental Hmox1 promoter. These stress-triggered changes were accompanied by an altered CD8+ T cell response, as evidenced by a reduction of tolerogenic CD8+CD122+ T cells and an increase of cytotoxic CD8+ T cells. Using progesterone receptor- or Hmox1-deficient mice, we identified progesterone as an upstream modulator of placental Hmox1 expression. Supplementation of progesterone or depletion of CD8+ T cells revealed that progesterone suppresses CD8+ T cell cytotoxicity, whereas the generation of CD8+C...Continue Reading

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Citations

Mar 20, 2016·Placenta·María Emilia SolanoPetra Clara Arck
Aug 13, 2015·American Journal of Obstetrics and Gynecology·Amy-Eunice FurcronNardhy Gomez-Lopez
Feb 26, 2016·Cell Adhesion & Migration·Ina Annelies StelzerMaria Emilia Solano
Jul 29, 2016·Seminars in Immunopathology·María Emilia SolanoEva Tolosa
Mar 21, 2018·Clinical and Experimental Hypertension : CHE·Mahnaz RezaeiSaeedeh Salimi
Sep 9, 2016·Physiological Reviews·Anita AyerRoland Stocker
Jan 4, 2019·American Journal of Reproductive Immunology : AJRI·Alexandra Maximiliane HierwegerPetra Clara Arck
Mar 29, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marcia Arenas-HernandezNardhy Gomez-Lopez
Apr 30, 2020·Human Reproduction Update·Katell Peoc'hThierry Fournier
Jul 6, 2015·Oncotarget·María Emilia Solano, Petra Clara Arck
Jan 5, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jan Broder EnglerManuel A Friese
Aug 25, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jan Broder EnglerManuel A Friese
Oct 10, 2018·Seminars in Immunopathology·Dimitra E Zazara, Petra Clara Arck
Aug 4, 2016·Reproductive Sciences·Kohji KunishigeHiromichi Tamada
Feb 11, 2020·Frontiers in Immunology·Maria Emilia Solano, Petra Clara Arck
Oct 20, 2020·Placenta·Rikako InoueReiko Akagi

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Methods Mentioned

BETA
transgenic
genotyping
PCR
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PMA
flow cytometry
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FlowJo
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