The Long and Short of It: The Role of Telomeres in Fetal Origins of Adult Disease

Abstract

Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or cellular senescence through increased oxidative stress and DNA damage to telomeric ends may be initiators of these disease processes. This paper will explore the areas where telomere and telomerase biology can have significant effects on various tissues in the body in IUGR outcomes.

Transcriptional signatures throughout development: the effects of mouse embryo manipulation in vitro

“…2000, Sakai, et al 2003). ROS can also impair telomerase activity, with telomere attrition being a predictive marker for cardiovascular dysfunction, metabolic syndrome and other age- and DOHaD-related pathologies (Hallows, et al 2012). It is therefore possible that an in increase in ROS levels is the initial stimulus that reprograms the ART embryo, which employs transcription factors like NFE2L2, CEBPs (Manea, et al 2014), and p53 to exert acute transcriptional responses and subsequent chromatin remodeling that persists throughout development, leading to different cell type-contextual expression patterns.…”

Nutritional epigenetics with a focus on amino acids: implications for the development and treatment of metabolic syndrome

“…Growing epidemiological evidence shows that malnutrition of pregnant women is positively associated with the development of diabetes in their offspring [31][32][33]. Results of experiments with the rat model have demonstrated that limited protein intake during pregnancy may reduce liver X receptor offspring α (LXRα) histone promoter region H3 (K9, 14) acetylation, thus silencing expression of LXRα, which in turn increases expression of its target gene 11β-HSD1…”

Aging of intrauterine tissues in spontaneous preterm birth and preterm premature rupture of the membranes: A systematic review of the literature

“…Shorter telomeres have been reported in trophoblasts from pregnancies with preeclampsia and intrauterine growth restriction, compared to uncomplicated pregnancies [16]. Moreover, oxidative stress and DNA damage to telomeric ends, as well as decreased telomerase activity can lead to premature placental aging and these findings have been implicated in the etiology of intrauterine growth restriction [18,19].…”