Preconception telomere length as a novel maternal biomarker to assess the risk of spina bifida in the offspring

Abstract

Background Periconception interactions between maternal conditions and environmental and genetic factors are involved in the pathogenesis and prevention of neural tube defects (NTD), such as spina bifida. These factors have in common that they can impair the oxidative pathway, resulting in excessive (chronic) oxidative stress and inflammation. Methods Review of the literature concerning underlying mechanisms and biomarkers of aging particularly during reproduction. A number of molecular markers for biological aging have been identified, including telomere length (TL). Excessive telomere shortening is an index of senescence, causes genomic instability and is associated with a higher risk of age‐related diseases. Furthermore, TL shortening is associated with the similar environmental and lifestyle exposures associated with NTD risk. Results Embryonic mice deficient in the telomerase gene show shorter TL and failure of closure of the neural tube as the main defect, suggesting that this developmental process is among the most sensitive to telomere loss and chromosomal instability. Conclusions From this background, we hypothesize that preconceptional long term exposure to harmful environmental and lifestyle risk factors accelerates a woman's aging process, which can be measured by TL, and thereby her underlying risk of NTD offspring. Alternatively, it might be that women with an increased NTD risk already exhibit a more advanced biological age before the onset of pregnancy compared to women of identical calendar age.

Shorter periconception maternal telomere length and the risk of congenital cardiac outflow defects in the offspring

“…Previous studies in mice showed that, embryonic mice deficient in the telomerase gene show shorter TL and failure of closure of the neural tube as the main defect, suggesting that this developmental process is sensitive to telomere loss and chromosomal instability 12,25 . These results support our findings, considering the similar risk factors neural tube defects and COD share.…”

“…A hypothetical role of TL in neural tube defects (NTD) and COD is illustrated by the epidemiological and biological evidence of the association between hyperhomocysteinemia and increased risk of NTD and COD in offspring 5,12 . Hyperhomocysteinemia is a sensitive biomarker of oxidative stress and as such may reduce the synthesis or increase the damage of DNA, including the telomeres.…”

“…Recent findings showed that newborn TL determines the adult TL 10 . It has been suggested that TL is a long‐term biomarker of chronic oxidative stress compared with hyperhomocysteinemia as short‐term biomarker 11,12 …”

Praktischer Ansatz für die Diagnose von Wirbelsäulendysplasien

“…Spinale Dysraphien sind eine Gruppe von Entwicklungsstörungen mit einer multifaktoriellen Ätiologie, die genetische, umweltbedingte und ernährungsbedingte Komponenten umfasst 6 7 .…”

Transfection of STAT3 overexpression plasmid mediated through recombinant lentivirus promotes differentiation of bone marrow mesenchymal stem cells into neural cells in fetal rats with spina bifida aperta

“…SBA's origin and pathophysiology aren't completely understood. However, it is widely assumed that embryonic development is influenced by a range of aberrant gene regulation and adverse environmental variables [ 2 ]. Apoptosis is a critical process in the growth, maturation, and creation of the nervous system [ 3 ].…”