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7: Telomere shortening in stillbirth: a sign of premature placental senescence

      Objective

      Although the direct pathogenic causes of stillbirth (SB) remain unknown, a substantial number of SBs are associated with abnormal placental development and functions. The objective of this study was to evaluate placental telomere shortening as an indicator of premature senescence and oxidative stress in SB.

      Study Design

      Placental tissue was collected from 27 antepartum unexplained SB (> 22 weeks) from a consecutive series of 51. Thirty-seven healthy controls (term) were randomly collected, matched for maternal age and ethnicity. SB was categorized as unexplained after an extensive workup to exclude known causes such as congenital/genetic anomalies, infection, twin to twin transfusion syndrome and hypoxia. DNA was extracted from the placenta for telomere length analysis using real time PCR. Standard curves were generated for telomere lengths from single copy gene amplifications using reference DNA. The telomere length for each sample was based on the ratio of telomere length of the sample to the single copy gene standard (T/S ratio) using the formula: ΔCt [Ct(telomere sample)/Ct(single gene)]. Telomere length was expressed as a relative T/S ratio normalized to the average T/S ratio of the reference sample [2-(ΔCtx -ΔCtr) = 2-ΔΔCt]. ANOVA was used for statistical analysis.

      Results

      Placental telomere length was 3 fold lower in SBs compared with control (T/S mean + SD: 2.604±1.204 vs. 7.406 ±8.035; p < 0.001). When data were stratified by early (< 34 weeks; mean gest age 27.8 weeks) and late SBs (above 34 weeks; mean gest age 38.25 weeks), telomere lengths remained significantly lower (early SB T/S: 2.193±1.21; late SBs T/S: 3.208±0.93; both p < 0.01 compared to control).

      Conclusion

      Reduction in telomere length in SBs is indicative of placental senescence likely due to oxidative stress in response to specific risk exposure. These data support a role for premature placental ageing in the etiology of unexplained SBs and provide a novel mechanistic insight.
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