Uteroplacental Insufficiency with Hypoxia Upregulates Placental PPARγ-KMT5A Axis in the Rat

Emily Barrett, Amy Loverin, Haimei Wang, Michelle Carlson, Tricia D. Larsen, Mariana M. Almeida, Jenna Whitman, Michelle L. Baack, Lisa A. Joss-Moore

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The placenta represents a critical node in fetal lipid acquisition, yet the mechanisms by which the placenta handles lipids under normal and pathologic conditions are incompletely understood. A key player in placental lipid handling is peroxisome proliferator–activated receptor gamma (PPARγ). PPARγ influences global gene expression via its regulation of the epigenetic modifier lysine methyltransferase 5A (KMT5A), which places a methyl group on histone 4 lysine 20 (H4K20me) of target genes. Here we test the hypothesis that KMT5A is present in both the human and rat placentas and is affected by uteroplacental insufficiency (UPI) in the rat in association with increased placental lipid accumulation. We assessed levels and localization of KMT5A, as well as lipid droplet accumulation, in human placental tissue collected from maternal donors after delivery by planned cesarean section. Using a rat model of UPI, we also evaluated the effects of UPI on lipid accumulation, PPARγ, KMT5A, and H4K20me in the rat placenta. In this study, we show for the first time the presence and activity of KMT5A, in human and in rat placentas. We also demonstrate that in the rat placenta, UPI increases hypoxia, KMT5a expression, and activity in association with increased lipid accumulation in placenta supporting male fetuses. Placental PPARγ-KMT5A axis may be an important mediator of placental lipid handling.

Original languageEnglish (US)
Pages (from-to)1476-1488
Number of pages13
JournalReproductive Sciences
Volume28
Issue number5
DOIs
StatePublished - May 2021

Keywords

  • Epigenetics
  • Lysine methyltransferase 5A
  • PPARγ
  • Placental lipid regulation

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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