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Acute Hypoxia and Chronic Ischemia Induce Differential Total Changes in Placental Epigenetic Modifications

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Abstract

Preeclampsia is a common obstetrical complication, hallmarked by new-onset hypertension. Believed to result from placental insufficiency and chronic placental ischemia, the symptoms of preeclampsia are caused by release of pathogenic factors from the placenta itself, although the mechanisms of their regulation are in many cases unknown. One potential mechanism is through changes in placental epigenetic chromatin modifications, particularly histone acetylation and DNA methylation. Here, we determined the effects of chronic ischemia on global epigenetic modifications in the rodent placenta in vivo and acute hypoxia in BeWo placental trophoblast cells in vitro. Placental insufficiency via uterine artery restriction increased maternal blood pressure and fetal demise while decreasing placental and fetal mass. Global placental histone H3 acetylation levels were significantly decreased at H3 K9, K14, K18, K27, and K56. Interestingly, when BeWo-immortalized placental trophoblast cells were cultured in oxygen concentrations mimicking healthy and ischemic placentas, there was a significant increase in acetylated at K9, K18, K27, and K56. This was associated with a small but significant decrease in placental acetyl-CoA, suggesting depletion in the source of acetyl group donors. Finally, while global methylation of cytosine from placental DNA was low in both groups of animals (<1%), there was ∼50% increase in 5-mC in response to chronic ischemia. This suggests acute hypoxia and chronic ischemia induce differential global changes in histone acetylation in the placenta and that chronically altered metabolic profiles could affect histone acetylation in the placenta, thereby regulating production of pathogenic factors from the placenta during preeclampsia.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State St, Jackson, MS, 39216, USA

    Adrian C. Eddy BS, Heather Chapman BS & Eric M. George PhD

  2. Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA

    Eric M. George PhD

Authors
  1. Adrian C. Eddy BS
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  2. Heather Chapman BS
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  3. Eric M. George PhD
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Correspondence to Eric M. George PhD.

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Eddy, A.C., Chapman, H. & George, E.M. Acute Hypoxia and Chronic Ischemia Induce Differential Total Changes in Placental Epigenetic Modifications. Reprod. Sci. 26, 766–773 (2019). https://doi.org/10.1177/1933719118799193

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