Placenta · 2025
Shorter umbilical cord telomere length is associated with fetal developmental anomalies and pregnancy loss.
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Goumy Carole, Sudy Thérèse, Coudrieu Océane, Ouedraogo Zangbéwendé Guy, Murer Nicolas, Darcha Claude, Darcha Camille, Veronese Lauren, Tchirkov Andrei
Аннотация
INTRODUCTION: Maintaining telomere length (TL) is crucial for cell division during embryogenesis and morphogenesis. Our initial study, conducted on amniotic fluid and chorionic villi samples, have suggested a link between shortened telomeres and abnormal fetal development. This new study aims to confirm these findings in umbilical cord (UC) samples.
METHODS: TL was analyzed by qPCR in 204 UC samples collected from cases of pregnancy loss, including 130 cases without developmental abnormalities, 62 with congenital malformations, and 12 with intrauterine growth restriction (IUGR). UC samples (n = 21) obtained from planned caesarean sections without fetal or neonatal distress were used as controls.
RESULTS: We observed a significant reduction of TL in case of malformations and IUGR (P < 0.0001). We observed that the reduction of TL was associated with the severity of malformations. We also analyzed TL according to the type of pregnancy loss. A significantly lower TL was observed in cases of spontaneous abortion (P = 0.002).
DISCUSSION: Our results show associations between the presence of UC short telomeres and the occurrence of congenital malformation, IUGR, and spontaneous abortion. An UC biopsy is a minimally invasive sample that can be easily obtained at birth and is suitable for studying fetal telomere biology in cases of developmental anomalies. Our hypothesis is that a defect in the mechanisms of TL maintenance would lead to the presence of short telomeres, limiting the proliferative capacity of embryonic cells and altering organogenesis and development. In clinical practice, geneticists should pay particular attention to genes involved in TL regulation when interpreting genome sequencing data, especially in cases of developmental abnormalities or recurrent miscarriages.
METHODS: TL was analyzed by qPCR in 204 UC samples collected from cases of pregnancy loss, including 130 cases without developmental abnormalities, 62 with congenital malformations, and 12 with intrauterine growth restriction (IUGR). UC samples (n = 21) obtained from planned caesarean sections without fetal or neonatal distress were used as controls.
RESULTS: We observed a significant reduction of TL in case of malformations and IUGR (P < 0.0001). We observed that the reduction of TL was associated with the severity of malformations. We also analyzed TL according to the type of pregnancy loss. A significantly lower TL was observed in cases of spontaneous abortion (P = 0.002).
DISCUSSION: Our results show associations between the presence of UC short telomeres and the occurrence of congenital malformation, IUGR, and spontaneous abortion. An UC biopsy is a minimally invasive sample that can be easily obtained at birth and is suitable for studying fetal telomere biology in cases of developmental anomalies. Our hypothesis is that a defect in the mechanisms of TL maintenance would lead to the presence of short telomeres, limiting the proliferative capacity of embryonic cells and altering organogenesis and development. In clinical practice, geneticists should pay particular attention to genes involved in TL regulation when interpreting genome sequencing data, especially in cases of developmental abnormalities or recurrent miscarriages.