Immunological Basis of In Utero Programming of Adult Disease

  • Thea N. Golden
  • Rebecca A. SimmonsEmail author
Part of the Healthy Ageing and Longevity book series (HAL, volume 9)


The in utero environment is critically important to fetal development and perturbations have been linked to adult diseases. Landmark studies from the Dutch famine showed that babies with low birth weights had significantly higher obesity rates as adults. In several other studies, low birth weight has been correlated with development of type 2 diabetes (T2D), cardiovascular disease and obesity. Maternal diseases, such as hypertension and gestational diabetes, also increase the risk of developing metabolic diseases as an adult. The immune system is implicated in the development of metabolic diseases. The fetal immune system is tolerant of its environment so as to prevent mounting an attack against maternal antigens. At birth, immune cells shift towards a pro-inflammatory phenotype. Disturbances to this delicate balance have been linked to metabolic diseases. In animal models of high maternal corticosteroids and intrauterine growth restriction (IUGR), pups are born with low birth weights and develop type 2 diabetes (T2D) as adults. In the IUGR model, development of T2D is dependent on interleukin 4 in the neonatal period. Development of the fetal immune system has the potential to effect offspring metabolic health.


In utero programming Intrauterine growth restriction Fetal immune system Pro-inflammatory phenotype Adult disease Metabolic health 


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Center for Research on Reproduction and Women’s Health, Perelman School of Medicine, University of PennsylvaniaPhiladelphiaUSA

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