Abstract
The present study investigates telomere length (TL) in dividing chorionic cytotrophoblast cells from karyotypically normal and abnormal first trimester miscarriages and ongoing pregnancies. Using Q-FISH, we measured relative TLs in the metaphase chromosomes of 61 chorionic villous samples. Relative TLs did not differ between karyotypically normal samples from miscarriages and those from ongoing pregnancies (p = 0.3739). However, among the karyotypically abnormal samples, relative TLs were significantly higher in ongoing pregnancies than in miscarriages (p < 0.0001). Relative TLs were also significantly higher in chorion samples from karyotypically abnormal ongoing pregnancies than in those from karyotypically normal ones (p = 0.0018) in contrast to miscarriages, where relative TL values were higher in the karyotypically normal samples (p = 0.002). In the karyotypically abnormal chorionic cytotrophoblast, the TL variance was significantly lower than in any other group (p < 0.05). Assessed by TL ratios between sister chromatids, interchromatid TL asymmetry demonstrated similar patterns across all of the chorion samples (p = 0.22) but significantly exceeded that in PHA-stimulated lymphocytes (p < 0.0001, p = 0.0003). The longer telomere was predominantly present in the hydroxymethylated sister chromatid in chromosomes featuring hemihydroxymethylation (containing 5-hydroxymethylcytosine in only one sister chromatid)—a typical sign of chorionic cytotrophoblast cells. Our results suggest that the phenomena of interchromatid TL asymmetry and its association to 5hmC patterns in chorionic cytotrophoblast, which are potentially linked to telomere lengthening through recombination, are inherent to the development programme. The TL differences in chorionic cytotrophoblast that are associated with karyotype and embryo viability seem to be determined by heredity rather than telomere elongation mechanisms. The inheritance of long telomeres by a karyotypically abnormal embryo promotes his development, whereas TL in karyotypically normal first-trimester embryos does not seem to have a considerable impact on developmental capacity.
Highlights
Telomeres are dynamic nucleoprotein structures consisting of DNA tandem repeats50 -TTAGGG-30, shelterin proteins and telomere repeat-containing RNA (TERRA) [1,2,3,4,5].Telomeres cap the ends of linear chromosomes, protecting them from degradation by endonucleases and end-to-end fusions [6,7,8]
In the absence of telomere-lengthening mechanisms, a cell that has undergone a certain number of replication rounds or adverse exposures enters senescence frequently accompanying by chromosomal instability and chromothripsis [17,18] and, eventually, apoptosis
The present study focuses on investigating Telomere length (TL) in the first trimester of gestation—a period marked by a robust natural negative selection of embryos with both anomalous and normal karyotypes, which results in 15%
Summary
Telomeres are dynamic nucleoprotein structures consisting of DNA tandem repeats50 -TTAGGG-30 , shelterin proteins and telomere repeat-containing RNA (TERRA) [1,2,3,4,5].Telomeres cap the ends of linear chromosomes, protecting them from degradation by endonucleases and end-to-end fusions [6,7,8]. Telomeres are dynamic nucleoprotein structures consisting of DNA tandem repeats. Telomere length (TL) in a chromosome is determined by the number of tandemly repeated hexanucleotides and depends on the balance between the mechanisms of telomere attrition and lengthening. Telomeres shorten with each cell division cycle because of the incomplete DNA replication of linear chromosomes by DNA polymerase [9]. Apart from mitotic activity, telomere shortening may be caused by several other factors, including DNA damage, inflammation and oxidative stress [10,11,12]. In the absence of telomere-lengthening mechanisms, a cell that has undergone a certain number of replication rounds or adverse exposures enters senescence frequently accompanying by chromosomal instability and chromothripsis [17,18] and, eventually, apoptosis. Adequate telomere length regulation is the sine qua non of a cell’s normal functioning
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