In utero exposure to endocrine-disrupting chemicals and telomere length at birth

University Of California Los Angeles, Los Angeles CA

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Abstract

? DESCRIPTION (provided by applicant): Telomere length is associated with longevity and with the risk for chronic diseases such as cardiovascular disease cancers. The relative ranking of a person's telomere length is largely determined at birth and subsequent telomeric erosion may be exacerbated by environmental factors which induce oxidative damage to the genome. This makes telomere length a prime mechanistic candidate to explain some of the observations of the Developmental Origins of Health and Disease (DOHaD), which connects perinatal events with long-term chronic disease susceptibility. Augmented telomere length at birth may have far-reaching implications with respect to overall health and chronic disease susceptibility throughout the life course. The prenatal period from conception to birth is of particular interest since it isthe phase of life marked by the most rapid physical growth and thus accelerated mitotic proliferation of cells. This may make the terminal restriction fragments particularly vulnerable to adverse intrauterine conditions. Surprisingly, few studies have considered the relevance of intrauterine conditions on telomere length. Specifically, hormonal factors have been implicated to play a role in the erosion of the terminal restriction fragments, suggesting that intrauterine exposure to endocrine- disrupting chemicals (EDCs) may disrupt hormonal signaling and telomere development. The impact of prenatal EDC exposure on telomere length has not previously been studied. We therefore propose to determine if maternal first trimester urinary phenol and phthalates levels are associated with telomere length of the offspring at birth using samples from the Harvard Epigenetic Birth Cohort at Brigham and Women's Hospital, Harvard Medical School, in Boston.