Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB069

Poster Communications

The Role of Receptors for Advanced Glycation End-products (RAGE) in the development of secondhand smoke (SHS)-induced intrauterine growth restriction (IUGR).

J. A. Arroyo1

1. Physiology and Developmental Biology, Brigham Young University, Provo, Utah, United States.

Intrauterine growth restriction (IUGR) is a disease affecting 10% of all pregnancies. IUGR is associated with prominent maternal, fetal, or placental abnormalities, but studies investigating the effects of secondhand smoke (SHS) exposure and IUGR induction are limited. Receptors for Advanced Glycation End-products (RAGE) are pro-inflammatory transmembrane receptors induced in the placenta during SHS exposure. We tested the hypothesis that RAGE activation propagates smoke-induced IUGR and is functionally relevant in health complications associated with IUGR offspring. Pregnant C57/Bl6 mice (n=8) were exposed to SHS or SHS and semi-synthetic glycosaminoglycan ethers (SAGEs) known to inhibit RAGE signaling. RAGE -/- mice were also exposed to SHS. At 4 weeks of age, offspring were weighed, and blood pressure and heart rate were determined. Whole body, heart and liver weights were also determined. Lastly, organ-specific mitochondrial function tests were performed. SHS treated mice demonstrated a significant reduction in fetal and placental weight compared to controls. Mice co-treated with SHS and SAGEs were protected from SHS-induced fetal weights decreases. SHS treatment of C57Bl6 mice activated placental ERK, JNK, and p38 and the expression of inflammatory mediators including TNF-α and IL-1β. SHS-mediated activation of these molecules was reduced to basal levels when RAGE signaling was targeted by SAGE. At 4 weeks of age, antenatal exposure of SHS still caused: 1) a significant reduction in total body weight; 2) significantly elevated systolic and diastolic blood pressure; 3) no differences in the animal's heart rate; 4) significantly decreased heart and kidney weights; and 5) significantly decreased oxygen consumption related to cellular respiration in SHS-exposed hearts and lungs when compared to organs from room air exposed controls. We conclude that inhibition of RAGE protects against fetal weight loss during SHS-induced IUGR. Our results further suggest that there is a direct correlation between RAGE activation and the development of IUGR during SHS. Furthermore, we conclude that antenatal exposure to SHS impacts the placenta and induces detrimental effects on growth rates and cardiopulmonary energetics through the 4th week of age, or the equivalent of early adolescence. These studies provide insight into tobacco-mediated IUGR development and clarify avenues that may be helpful in the alleviation of placental complications. Also, these studies may be beneficial in understanding the long-term effects of antenatal SHS exposure.

Where applicable, experiments conform with Society ethical requirements