Tumor Necrosis Factor Alpha Inhibition Improves Fetal Growth in a Rat Model of Preeclampsia

Authors

• Laura E. Coats, University of Mississippi Medical Center
• Nathan Campbell, University of Mississippi Medical Center
• Dylan Solise, University of Mississippi Medical Center
• Gabrielle M. Chamoun, University of Mississippi Medical Center
• Adam Z. Rawls, University of Mississippi Medical Center
• Alexandra Demesa, University of Mississippi Medical Center
• Ty Turner, University of Mississippi Medical Center
• Baoying Zheng, University of Mississippi Medical Center
• Barbara T. Alexander, University of Mississippi Medical Center
• Babbette LaMarca, University of Mississippi Medical Center

Author Type

faculty

Document Type

Article

Source Publication Title

Placenta

Abstract

Introduction

Tumor necrosis factor alpha (TNF-α) is elevated 2-fold in women with preeclampsia. Preclinical investigation shows TNF-α blockade reduces maternal blood pressure in reduced uterine perfusion pressure (RUPP) rats and attenuates the reduction in fetal weight. However, the benefits versus harms of this therapy on fetal growth and underlying pathogenesis are unknown. Thus, this study tested the hypothesis that maternal treatment with the soluble TNF-α inhibitor Etanercept (Etan) during late gestation improves placental perfusion, nutrient transport, and morphology, thereby improving fetal growth in the RUPP model of preeclampsia compared with Sham controls. We further hypothesized that maternal Etan treatment is associated with improved blood pressure and inflammatory profiles in offspring.

Methods

Sham or RUPP surgery was performed at gestational day (GD) 14, with vehicle or Etan (0.4 mg/kg, s.c.) administered at GD18.

Results

Fetal weight (p = 0.0365) and survival (p = 0.0002) were reduced in RUPP (p = 0.0365) at GD20; only fetal weight was improved in Etan-RUPP (p = 0.0480). At GD20, uterine artery resistance index (UARI) was increased in RUPP (p = 0.0094), but attenuated in Etan-RUPP, indicating improved placental perfusion. Impaired placental transport and morphology were evident in RUPP, with no improvement in Etan-RUPP. Birthweight was improved in Etan-RUPP (p = 0.0312), although total NK cells (p = 0.0376) were increased in female Etan-RUPP offspring. Circulating AT1-AA activity was elevated in adult male and female RUPP offspring (p = 0.0013, p = 0.0006), but attenuated in female Etan-RUPP offspring. Discussion: These results suggest improved fetal growth in Etan-RUPP, independent of placental morphology or nutrient transporter expression, with sex-specific effects on inflammation in adult RUPP offspring.

Graphical abstract

First Page

22

Last Page

30

DOI

https://doi.org/10.1016/j.placenta.2026.02.002

Publication Date

2-9-2026

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

Recommended Citation

Coats, Laura E.; Campbell, Nathan; Solise, Dylan; Chamoun, Gabrielle M.; Rawls, Adam Z.; Demesa, Alexandra; Turner, Ty; Zheng, Baoying; Alexander, Barbara T.; and LaMarca, Babbette, "Tumor Necrosis Factor Alpha Inhibition Improves Fetal Growth in a Rat Model of Preeclampsia" (2026). Physiology & Biophysics. 1.
https://digitalcollections.umc.edu/physandbio/1