ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Reduced uterine natural killer cell abundance and impaired spiral artery remodeling following intensive exercise performed before and during pregnancy in mice (#233)

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

Preeclampsia is a serious pregnancy complication associated with impaired spiral artery remodeling during placental development. Many women with preeclampsia have fewer regulatory T (Treg) cells, a subset of anti-inflammatory immune cells essential for maternal immune tolerance. We previously demonstrated in mice that Treg cell deficiency is a primary cause of impaired spiral artery remodeling, causing dysregulation of uterine natural killer (uNK) cells, a special category of NK cells. 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 pregnancy in mice would enhance the proportion of Treg and uNK cell abundance, leading to improved vascular adaptations and pregnancy outcomes. Exercise began 6 weeks prior to and throughout pregnancy in CBA/J mice on a rodent treadmill (5 days/week, 10 m/min, 30 min/day), while control mice remained sedentary. At mid-gestation (day 10.5 post coitum (pc)), Treg cells in the uterine-draining lymph nodes were assessed using flow cytometry, and uterine artery function, decidual spiral artery remodeling and uNK cell abundance were also analysed. Fetal and placental weights were assessed at late-gestation (day 18.5 pc). Intensive running exercise before and during pregnancy increased the proportion of Treg cells by 20%, and increased their expression of proliferation marker Ki67 by 35% (both P<0.05) at mid-gestation. Uterine artery haemodynamics were unchanged. Surprisingly, decidual spiral artery remodeling was impaired and uNK cell abundance was reduced (P<0.05). At late-gestation, fetal weights and fetal:placental weight ratios were reduced by 25% and 28%, respectively (both P<0.05) in exercised dams compared to sedentary dams. Persistent intensive running exercise before and during pregnancy increased Treg cell abundance, but impaired spiral artery remodeling and fetal growth. Current experiments with a moderate exercise regime aims to obtain these immune benefits without imposing excessive energy demands on the mother.