E-Poster Presentation ESA-SRB-ANZBMS 2021

Reduced uterine natural killer cell abundance and impaired spiral artery remodeling in mice performing intensive exercise before and during pregnancy (#560)

Evangeline A Lovell 1 , Shanna L Hosking 1 , Holly M Groome 1 , Glenn K McConell 2 , Lachlan M Moldenhauer 1 , Kathryn L Gatford 1 , Sarah A Robertson 1 , Alison S Care 1
  1. Obstetrics and Gynecology, Robinson Research Institute and School of Biomedicine, University of Adelaide, Adelaide, South Australia, Australia
  2. Robinson Research Institute and School of Biosciences, University of Adelaide, Adelaide, SA, Australia, University of Adelaide, Adelaide, SA, Australia

Introduction: Regulatory T (Treg) cells, a subset of anti-inflammatory immune cells, are essential for maternal immune tolerance and suppressing inflammation. Many women with preeclampsia have fewer Treg cells and preeclampsia is associated with impaired spiral artery remodeling.

In mice, Treg cells facilitate uterine artery function and spiral artery remodeling during early placental development. Exercise can increase Treg cell numbers in non-pregnant mice and enhance placental vascular volume in pregnant women. We therefore hypothesized that exercise before and during murine pregnancy would enhance Treg cell proportion and uterine natural killer (NK) cell abundance, leading to improved vascular adaptations and pregnancy outcomes.

Methods: Female CBA/J mice were exercised for 6 weeks prior to and throughout pregnancy on a treadmill (5 days/week, 10 m/min, 30 min/day). Control mice remained sedentary. On day 10.5 post coitum (pc), Treg cells in the uterine-draining lymph nodes (udLN) were assessed using flow cytometry, and uterine artery function, decidual spiral artery remodeling and uNK cell abundance were also analysed. On day 18.5 pc, fetal and placental weights were assessed.

Results: Intensive running exercise before and during pregnancy increased the proportion of Treg cells by 20%, along with a 35% increase in expression of the proliferation marker Ki67 (both p<0.05) at day 10.5 pc. Uterine artery haemodynamics were unchanged. Unexpectedly, decidual spiral artery remodeling was impaired and uNK cell abundance was reduced. At the end of pregnancy, fetal weight and the fetal:placental weight ratio were reduced by 25% and 28% respectively (both p<0.05) in exercised compared to sedentary dams.

Conclusion: Continued intensive running exercise before and during pregnancy increased Treg cell abundance, but impaired spiral artery remodeling and fetal growth. Ongoing experiments will assess whether a moderate exercise regime can obtain immune benefits without imposing excessive energy demands on the mother that may impair fetal outcomes after intensive exercise.