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Pharmacological activation of peroxisome proliferator‐activated receptor γ (PPAR‐γ) protects against hypoxia‐associated fetal growth restriction
Author(s) -
Lane Sydney L.,
Blair Dodson R.,
Doyle Alexandrea S.,
Park Haemin,
Rathi Hinal,
Matarrazo Christopher J.,
Moore Lorna G.,
Lorca Ramón A.,
Wolfson Gabriel H.,
Julian Colleen G.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201900214r
Subject(s) - endocrinology , intrauterine growth restriction , peroxisome proliferator activated receptor , medicine , hypoxia (environmental) , placental insufficiency , preeclampsia , fetus , placenta , biology , receptor , pregnancy , chemistry , genetics , organic chemistry , oxygen
The hypoxia of high‐altitude (HA) residence increases the risk of intrauterine growth restriction (IUGR) and preeclampsia 3‐fold, augmenting perinatal morbidity and mortality and the risk for childhood and adult disease. Currently, no effective therapies exist to prevent these vascular disorders of pregnancy. The peroxisome proliferator‐activated receptor γ (PPAR‐γ) is an important regulator of uteroplacental vascular development and function and has been implicated in the pathogenesis of IUGR and preeclampsia. Here, we used a model of HA pregnancy in mice to determine whether hypoxia‐induced fetal growth restriction reduces placental PPAR‐γ protein expression and placental vascularization and, if so, to evaluate the effectiveness of the selective PPAR‐γ agonist pioglitazone (PIO) for preventing hypoxia‐induced IUGR. Hypoxia resulted in asymmetric IUGR, placental insufficiency, and reduced placental PPAR‐γ expression; PIO prevented approximately half of the fetal growth restriction and attenuated placental insufficiency. PIO did not affect fetal growth under normoxia. Although PIO was beneficial for fetal growth, PIO treatment reduced placental vascular density of the labrynthine zone in normoxic and hypoxic (Hx) conditions, and mean vascular area was reduced in the Hx group. Our results suggest that pharmacological PPAR‐γ activation is a potential strategy for preventing IUGR in pregnancies complicated by hypoxia, although further studies are needed to identify its likely metabolic or vascular mechanisms.—Lane, S. L., Dodson, R. B., Doyle, A. S., Park, H., Rathi, H., Matarrazo, C. J., Moore, L. G., Lorca, R. A., Wolf son, G. H. Julian, C. G. Pharmacological activation of peroxisome proliferator‐activated receptor γ (PPAR‐γ) protects against hypoxia‐associated fetal growth restriction. FASEB J. 33, 8999–9007 (2019). www.fasebj.org