Telomere length is associated with longevity and with the risk for chronic diseases such as cardiovascular disease and cancer. The relative ranking of a person's telomere length is largely determined at birth and subsequent telomeric erosion may be exacerbated by environmental factors. 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 antenatal events with the propensity of chronic disease. 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 is the phase of life marked by the most rapi 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 the intrauterine environment 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. With detectable levels of phthalates and phenols in pregnant women and infants there is potential for these chemicals to adversely affect normal human growth and 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 phthalates and/or phenol 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.
How telomere length ranks among individuals throughout the life course is determined prenatally. The large variation in telomere length at birth suggests important influences of the intrauterine environment on telomere dynamics. We propose to examine the influence of in utero exposure to endocrine-disrupting chemicals on telomere length at birth.
