TY - JOUR
T1 - Uteroplacental Insufficiency with Hypoxia Upregulates Placental PPARγ-KMT5A Axis in the Rat
AU - Barrett, Emily
AU - Loverin, Amy
AU - Wang, Haimei
AU - Carlson, Michelle
AU - Larsen, Tricia D.
AU - Almeida, Mariana M.
AU - Whitman, Jenna
AU - Baack, Michelle L.
AU - Joss-Moore, Lisa A.
N1 - Funding Information:
This study was supported in part through National Institutes of Health (NIH) DK084036 (LJM) and NIH/NIGMS: 2P20GM103620-06, Sanford Research Experience for Undergraduates (SPUR) NSF REU:1756912 (MLB), and the Division of Neonatology, Department of Pediatrics at the University of Utah.
Publisher Copyright:
© 2021, Society for Reproductive Investigation.
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
KW - Epigenetics
KW - Lysine methyltransferase 5A
KW - PPARγ
KW - Placental lipid regulation
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U2 - 10.1007/s43032-020-00434-w
DO - 10.1007/s43032-020-00434-w
M3 - Article
C2 - 33398850
AN - SCOPUS:85098626086
SN - 1933-7191
VL - 28
SP - 1476
EP - 1488
JO - Reproductive Sciences
JF - Reproductive Sciences
IS - 5
ER -