Sonja Entringer1, Elissa S Epel, Jue Lin, Elizabeth H Blackburn, Claudia Buss, Hyagriv N Simhan, Pathik D Wadhwa. 1. Departments of Pediatrics (S.E., C.B., P.D.W.), Obstetrics and Gynecology (P.D.W.), Epidemiology (P.D.W.), and Psychiatry and Human Behavior (P.D.W.), University of California, Irvine; California 92697; Department of Obstetrics, Gynecology, and Reproductive Sciences (H.N.S.), University of Pittsburgh, Pittsburgh, Pennsylvania 15213; Departments of Psychiatry (E.S.E.), and Biochemistry and Biophysics (E.H.B.), University of California, San Francisco, San Francisco, California 94143; and Institute for Medical Psychology (S.E., C.B.), Charité University Medicine, 10117 Berlin, Germany.
Abstract
CONTEXT: Telomere biology plays a fundamental role in genomic integrity, cellular regeneration, physiology, aging, disease risk, and mortality. The initial setting of telomere length (TL) in early life has important implications for telomere maintenance and related disorders throughout the life span. However, little is known about the predictors of this initial setting. OBJECTIVE: Given the established role of estrogen on adult TL and the role of estriol (E3) in the context of fetal development, the goal of this study was to test the hypothesis that higher maternal E3 concentration during early pregnancy is associated with longer infant telomere length. DESIGN, PARTICIPANTS, AND SETTING: Study participants comprised a cohort of N = 100 infants followed prospectively from intrauterine life and birth through early childhood from a population-based, representative sample of pregnant mothers recruited in early pregnancy at university-based obstetric clinics in Southern California. Maternal unconjugated E3 concentrations were assessed in plasma in early gestation (around wk 15). Infant TL was assessed in buccal cells at approximately 15 months of age. RESULTS: After accounting for the effects of potential confounding maternal and infant variables, there was a significant, independent effect of maternal E3 concentration on infant TL (unstandardized β = 0.297; P = .001; 95% Cl, 0.121-0.473). Specifically, a one-multiple-of-the-median (MoM) increase in maternal E3 concentration during early pregnancy was associated with a 14.42% increase in infant TL. CONCLUSIONS: This study supports the concept of developmental plasticity of the telomere biology system and highlights specifically the role of a potentially modifiable intrauterine factor for additional mechanistic and clinical investigation.
CONTEXT: Telomere biology plays a fundamental role in genomic integrity, cellular regeneration, physiology, aging, disease risk, and mortality. The initial setting of telomere length (TL) in early life has important implications for telomere maintenance and related disorders throughout the life span. However, little is known about the predictors of this initial setting. OBJECTIVE: Given the established role of estrogen on adult TL and the role of estriol (E3) in the context of fetal development, the goal of this study was to test the hypothesis that higher maternal E3 concentration during early pregnancy is associated with longer infant telomere length. DESIGN, PARTICIPANTS, AND SETTING: Study participants comprised a cohort of N = 100 infants followed prospectively from intrauterine life and birth through early childhood from a population-based, representative sample of pregnant mothers recruited in early pregnancy at university-based obstetric clinics in Southern California. Maternal unconjugated E3 concentrations were assessed in plasma in early gestation (around wk 15). Infant TL was assessed in buccal cells at approximately 15 months of age. RESULTS: After accounting for the effects of potential confounding maternal and infant variables, there was a significant, independent effect of maternal E3 concentration on infant TL (unstandardized β = 0.297; P = .001; 95% Cl, 0.121-0.473). Specifically, a one-multiple-of-the-median (MoM) increase in maternal E3 concentration during early pregnancy was associated with a 14.42% increase in infant TL. CONCLUSIONS: This study supports the concept of developmental plasticity of the telomere biology system and highlights specifically the role of a potentially modifiable intrauterine factor for additional mechanistic and clinical investigation.
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