Open Access

ARTICLE

Reversal of maternal obesity attenuates hypoxia and improves placental development in the preeclamptic-like BPH/5 mouse model

by DANIELLA M. ADAMS¹, KALIE F. BECKERS¹, JULIET P. FLANAGAN¹, VIVIANE C. L. GOMES^1,#, CHIN-CHI LIU¹, JENNY L. SONES^1,2,*

1 Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA
2 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA

* Corresponding Author: JENNY L. SONES. Email:
# Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA

BIOCELL 2023, 47(9), 2051-2058. https://doi.org/10.32604/biocell.2023.029644

Received 28 February 2023; Accepted 06 July 2023; Issue published 28 September 2023

Abstract

Background: Women with obesity have higher risk of adverse pregnancy outcomes, including preeclampsia (PE). Late-gestational hypertension, aberrant fetoplacental development, and fetal growth restriction (FGR), hallmarks of PE, are observed spontaneously in BPH/5 mice. Similar to obese preeclamptic women, BPH/5 mice have higher visceral white adipose tissue (WAT) and circulating leptin. We hypothesized that attenuation of maternal obesity and serum leptin in pregnant BPH/5 mice will improve fetoplacental development by decreasing hypoxia markers and leptin expression at the maternal-fetal interface. Methods: To test this hypothesis, BPH/5 mice were fed ad libitum (lib) and pair-fed (PF) to C57 ad lib controls beginning at embryonic day (e) 0.5. Hypoxia-related genes, hypoxia inducible factor (Hif) 1α, stem cell factor (Scf), heme oxygenase-1 (Ho-1), leptin (Lep), and leptin receptor (LepR) were assessed in e7.5 implantation sites. Results: BPH/5 ad lib had 1.5 to 2-fold increase in Hif1α, Scf, and Ho-1 mRNA and a greater than 3-fold increase in leptin mRNA vs. C57 that was attenuated with PF. Exogenous leptin promoted Hif1α and Ho-1 mRNA expression in e7.5 decidua in vitro. While hypoxic conditions in vitro did not change decidual leptin mRNA. Furthermore, BPH/5 PF mice demonstrated improved fetal and placental outcomes later in gestation, with greater placental vascular area by e18.5 and attenuation of FGR. Conclusion: In conclusion, pair-feeding BPH/5 mice beginning at conception may improve placental vasculature formation via decreased leptin and hypoxia-associated markers in this model. Future investigations are needed to better determine the effect of hypoxia and leptin on pregnancy outcomes in obese pregnant women.

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