Abstract
Simple SummaryObesity increases the risk of problems during pregnancy, potentially due to inappropriate activation of the immune system. We predicted that, because of this immune activation, obesity in mice would exacerbate the effects of lipopolysaccharide (LPS), a substance that mimics infection, impairs fetal growth and leads to pregnancy loss in animal models. Mice were fed a high- or low-fat diet for thirteen weeks prior to mating, and then received an LPS or control injection during pregnancy. Treatment with LPS induced pregnancy loss in some mice, as expected. However, LPS did not have more severe effects in females fed the high-fat diet, who were heavier. Our results therefore do not support the hypothesis that an otherwise healthy obese pregnancy can be driven to an adverse outcome by a low-level infection. Our study improves the understanding of why obese women are at greater risk of adverse pregnancy outcomes. In doing so, it will contribute to future studies that seek to determine how obese pregnancies at risk of adverse outcomes can be distinguished from healthy obese pregnancies.Obesity increases the risk of a number of pregnancy complications, potentially due to chronic inflammation. We predicted that an obesogenic high-fat diet (HFD) in mice would create an inflammatory environment that would exacerbate the effects of lipopolysaccharide (LPS), an inflammatory insult, administered during pregnancy. Females were placed on a HFD or a low-fat diet (LFD) prior to mating, injected with 2 µg LPS or control on gestational day 7 and collected on day 14. Treatment with LPS increased the odds that a female thought to be pregnant at injection had no conceptuses at day 14 (p = 0.024), suggesting that injection with LPS was more likely to induce complete abortion. However, there was no effect of diet on the odds of having no conceptuses at day 14 and no interaction between diet and LPS injection. Diet and LPS injection had no effect on the number of viable fetuses in females still pregnant at day 14. For fetal weight, there was a significant interaction between diet and treatment (p = 0.017), whereby LPS reduced fetal weight in HFD females but not in LFD females. However, LPS treatment of HFD females reduced fetal weight to that observed in control-injected LFD females. Although LPS increased the odds of abortion, there was little evidence that a HFD exacerbated the effects of LPS.
Highlights
Obesity doubles to triples the risk of pregnancy complications such as miscarriage, stillbirth and preeclampsia [1,2,3,4]
It is hypothesized that increased adipose tissue results in elevated levels of pro-inflammatory cytokines in the blood [7,8,9], which influence the function of immune cells within the uterus [5], thereby impairing normal placental development and increasing the risk of adverse outcomes [10,11]
We recently reported that an obesogenic high-fat diet (HFD) fed to mice altered populations and activity of uterine natural killer cells, maternal immune cells that play a crucial role in placental development [12]
Summary
Obesity doubles to triples the risk of pregnancy complications such as miscarriage, stillbirth and preeclampsia [1,2,3,4]. While maternal obesity alone does not necessarily lead to complications, the associated chronic, low-grade inflammation might increase susceptibility to adverse outcomes when combined with an additional inflammatory challenge. We recently reported that an obesogenic high-fat diet (HFD) fed to mice altered populations and activity of uterine natural killer cells, maternal immune cells that play a crucial role in placental development [12]. This diet did not affect fetal weight and was not otherwise associated with adverse outcomes [12,13], suggesting that it models healthy obese pregnancy. We predicted that maternal obesity induced by a HFD would exacerbate the response to a low dose of LPS, leading to synergistic effects on fetal growth and survival
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have