D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya Line 3, 199034 Saint Petersburg, Russia.
Department of Medical Biophysics, Saint Petersburg State Pediatric Medical University, Litovskaya Street 2, 194100 Saint Petersburg, Russia.
Int J Mol Sci. 2021 Jun 21;22(12):6622. doi: 10.3390/ijms22126622.
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 ( = 0.3739). However, among the karyotypically abnormal samples, relative TLs were significantly higher in ongoing pregnancies than in miscarriages ( < 0.0001). Relative TLs were also significantly higher in chorion samples from karyotypically abnormal ongoing pregnancies than in those from karyotypically normal ones ( = 0.0018) in contrast to miscarriages, where relative TL values were higher in the karyotypically normal samples ( = 0.002). In the karyotypically abnormal chorionic cytotrophoblast, the TL variance was significantly lower than in any other group ( < 0.05). Assessed by TL ratios between sister chromatids, interchromatid TL asymmetry demonstrated similar patterns across all of the chorion samples ( = 0.22) but significantly exceeded that in PHA-stimulated lymphocytes ( < 0.0001, = 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.
本研究调查了来自核型正常和异常的早孕期自然流产及持续妊娠的绒毛细胞滋养层细胞中端粒长度 (TL)。通过 Q-FISH，我们测量了 61 例绒毛组织样本中期染色体的相对 TL。核型正常的流产样本和持续妊娠样本之间的相对 TL 没有差异（=0.3739）。然而，在核型异常的样本中，持续妊娠的相对 TL 明显高于流产（<0.0001）。与流产相比，核型异常持续妊娠的绒毛样本的相对 TL 也明显高于核型正常的样本（=0.0018），而在流产中，核型正常的样本的相对 TL 值更高（=0.002）。在核型异常的绒毛细胞滋养层中，TL 方差明显低于其他任何组（<0.05）。通过姐妹染色单体之间的 TL 比值评估，所有绒毛样本的染色单体间 TL 不对称性均显示出相似的模式（=0.22），但明显高于 PHA 刺激的淋巴细胞（<0.0001，=0.0003）。在具有半羟甲基化（仅一条姐妹染色单体中含有 5-羟甲基胞嘧啶）的染色体中，主要存在较长的端粒位于羟甲基化的姐妹染色单体上-这是绒毛细胞滋养层的典型特征。我们的研究结果表明，染色单体间 TL 不对称性及其与绒毛细胞滋养层中 5hmC 模式的关联现象，可能通过重组与端粒延长有关，是发育计划的固有特征。与核型和胚胎活力相关的绒毛细胞滋养层中的 TL 差异似乎是由遗传决定的，而不是由端粒延长机制决定的。核型异常胚胎继承长端粒促进其发育，而核型正常的早孕期胚胎的端粒长度似乎对发育能力没有显著影响。
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