Abstract
IntroductionTelomeres, are composed of tandem repeat sequences located at the ends of chromosomes and are required to maintain genomic stability. Telomeres can become shorter due to cell division and specific lifestyle factors. Critically shortened telomeres are linked to cellular dysfunction, senescence and aging. A number of studies have used low resolution techniques to assess telomere length in the placenta. In this study, we applied Single Telomere Length Analysis (STELA) which provides high-resolution chromosome specific telomere length profiles to ask whether we could obtain more detailed information on the length of individual telomeres in the placenta. MethodsTerm placentas (37–42 weeks) were collected from women delivering at University Hospital of Wales or Royal Gwent Hospital within 2 h of delivery. Multiple telomere-length distributions were determined using STELA. Intraplacental variation of telomere length was analysed (N = 5). Telomere length distributions were compared between labouring (N = 10) and non-labouring (N = 11) participants. Finally, telomere length was compared between female (N = 17) and male (N = 20) placenta. ResultsThere were no significant influences of sampling site, mode of delivery or foetal sex on the telomere-length distributions obtained. The mean telomere length was 7.7 kb ranging from 5.0 kb to 11.7 kb across all samples (N = 42) and longer compared with other human tissues at birth. STELA also revealed considerable telomere length heterogeneity within samples. ConclusionsWe have shown that STELA can be used to study telomere length homeostasis in the placenta regardless of sampling site, mode of delivery and foetal sex. Moreover, as each amplicon is derived from a single telomeric molecule, from a single cell, STELA can reveal the full detail of telomere-length distributions, including telomeres within the length ranges observed in senescent cells. STELA thus provides a new tool to interrogate the relationship between telomere length and pregnancy complications linked to placental dysfunction.
Highlights
Telomeres, are composed of tandem repeat sequences located at the ends of chromosomes and are required to maintain genomic stability
The placenta is exposed to the same environmental insults as the foetus and may provide a tool to assess the effect of environmental exposures on telomeres in pregnancy [14]
XpYp Single Telomere Length Analysis (STELA) was applied to a total of 42 unique placental samples to examine if the telomere length distributions varied according to intra-placental variation, mode of delivery and sex differences
Summary
Telomeres are present at the ends of all mammalian chromosomes [1] and are known to maintain genomic stability avoiding degradation and fusion events [2]. Studies in animals and humans suggest that intrauterine exposure to adverse conditions contribute to shorter telomeres at birth [13]. Shortened placental telomeres may functionally contribute to low birth weight [15e21]. The two most widely used methods, terminal restriction fragment analysis (TRF) and quantitative polymerase chain reaction (q-PCR) are suitable for estimation of mean telomere length or telomere repeat content respectively. Whilst STELA is comparatively low throughput, it is high-resolution and can detect the presence of telomeres within the length ranges that can lead to senescence, apoptosis and telomere fusion [26,27]. STELA has the potential to provide a richer and more detailed picture of telomere length in the placenta in relation to foetal growth restriction and perhaps provide more information on the role of adverse maternal lifestyles in telomere shortening. We examined the patient of XpYp telomere length analysis, using STELA, with respect to placental sampling site, mode of delivery and foetal sex
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