Impact of Phthalate Exposure on Telomere Biology in Utero

This proposal posits that phthalates, which are widely considered endocrine disrupting chemicals, interfere with human telomere biology in utero, leading to shortening of telomeres in the placenta and newborn. Specifically, it is hypothesized that phthalates alter the activity of telomerase through actions on hTERT, which encodes the catalytic subunit of the enzyme. As telomere length (TL) is largely determined at birth, prenatal exposure to phthalates could reset one’s lifelong TL trajectory with potential health effects during adulthood. Southern blotting (SB) and the Telomeres Shortest Length Assay (TeSLA) will be used to examine associations between prenatal phthalate exposure and TL parameters measured in the placenta-newborn unit. The placenta will further be leveraged to gain a mechanistic understanding of molecular outcomes related to phthalate exposure. This will be achieved by quantifying hTERT expression, telomerase activity, formation of telomere dysfunction- induced DNA damage foci (TIF), activation of cell cycle checkpoints and senescence markers in tandem with measuring TL parameters. TL measurements in umbilical cord blood and follow-up blood at approximately age 8 years will serve to test whether a putative phthalate effect on TL persists through the first decade of life. Generating longitudinal TL data will not only provide insight into the endurance of the phthalate effect, but will also fill a critical knowledge gap about early life TL dynamics. This research will leverage existing prenatal phthalate data and biobanked perinatal biospecimens (placenta and cord blood) from 500 mother-child pairs enrolled in the prospective New York University Children’s Health and Environment Study (NYU CHES). The proposal benefits from the strong collaboration between W. Cowell (Contact PI), an environmental and molecular epidemiologist with over 10 years of experience working with birth cohorts and A. Aviv (Co-PI), an expert in telomere biology. Knowledge gained can provide a foundation for the use of TL at birth as a biomarker of future health risk. TL measurements may thus become a precision tool that help gauge early risk for later life TL-linked diseases.