Tropomyosin Receptor Kinase B Agonist, 7,8-Dihydroxyflavone, Improves Mitochondrial Respiration in Placentas From Obese Women

Calais S. Prince, Alina Maloyan, Leslie Myatt

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Maternal obesity negatively impacts the placenta, being associated with increased inflammation, decreased mitochondrial respiration, decreased expression of brain-derived neurotrophic factor (BDNF), and its receptor, tropomyosin receptor kinase B (TRKB). TRKB induction by 7,8-dihydroxyflavone (7,8-DHF) improves energy expenditure in an obesity animal model. We hypothesized that TRKB activation would improve mitochondrial respiration in trophoblasts from placentas of obese women. Placentas were collected from lean (pre-pregnancy BMI < 25) and obese (pre-pregnancy BMI > 30) women at term following cesarean section delivery without labor. Cytotrophoblasts were isolated and plated, permitting syncytialization. At 72 hours, syncytiotrophoblasts (STs) were treated for 1 hour with 7,8-DHF (10 nM–10 M), TRKB antagonists (ANA-12 (10 nM–1 M), Cyclotraxin B (1 nM–1M)), or vehicle. Mitochondrial respiration was measured using the XF24 Extracellular Flux Analyzer. TRKB, MAPK, and PGC1α were measured using Western blotting. Maternal obesity was associated with decreased mitochondrial respiration in STs; however, 7,8-DHF increased basal, ATP-coupled, maximal, spare capacity, and nonmitochondrial respiration. A 10 μM dose of 7,8-DHF reduced spare capacity in STs from lean women, with no effect on other respiration parameters. 7,8-DHF had no effect on TRKB phosphorylation; however, there was a concentration-dependent decrease of p38 MAPK phosphorylation and increase of PGC1α in STs from obese, but not in lean women. TRKB antagonism attenuated ATP-coupled respiration, maximal respiration, and spare capacity in STs from lean and obese women. 7,8-DHF improves mitochondrial respiration in STs from obese women, suggesting that the obese phenotype in the placenta can be rescued by TRKB activation.

Original languageEnglish (US)
Pages (from-to)452-462
Number of pages11
JournalReproductive Sciences
Volume25
Issue number3
DOIs
StatePublished - Mar 1 2018

Keywords

  • mitochondrial respiration
  • neurotrophin
  • obesity
  • placenta

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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