Biron-Shental Tal, Sukenik-Halevy Rivka, Sharon Yudith, Laish Ido, Fejgin Moshe D, Amiel Aliza
Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Genetic Institute, Meir Medical Center, Kfar Saba, Israel.
Early Hum Dev. 2014 Sep;90(9):465-9. doi: 10.1016/j.earlhumdev.2014.06.003. Epub 2014 Jul 7.
Placentas from pregnancies complicated with IUGR (intrauterine growth restriction) express altered telomere homeostasis. In the current study, we examined mechanisms of telomere shortening in these placentas.
Placental biopsies from 15 IUGR and 15 healthy control pregnancies were examined. The percentage of trophoblasts with fragmented nuclei: senescence-associated heterochromatin foci (SAHF), was calculated using DAPI staining. The amount of human telomerase reverse transcriptase (hTERT) mRNA was evaluated using RtPCR levels of telomere capture using FISH in those samples were estimated.
The percentage of trophoblasts with SAHF was higher in IUGR compared to control samples, (25±13.4% vs. 1.6±1.6%, P<0.0001), hTERT mRNA was decreased (0.5±0.2 vs. 0.9±0.1, P<0.0001) and telomere capture was increased (13.2±9.7% vs.1.3±2.5%, P<0.001).
We suggest that IUGR placentas express increased signs of senescence as part of the impaired telomere homeostasis. One factor that mediates telomere shortening in these placentas is decreased hTERT mRNA, leading to decreased protein expression and therefore, reduced telomere elongation. Telomere capture, which is a healing process, is increased in IUGR trophoblasts as a compensatory mechanism.
患有宫内生长受限（IUGR）的妊娠胎盘表现出端粒稳态改变。在本研究中，我们研究了这些胎盘中端粒缩短的机制。
对15例IUGR妊娠和15例健康对照妊娠的胎盘活检样本进行检查。使用DAPI染色计算核碎片化的滋养层细胞百分比：衰老相关异染色质灶（SAHF）。使用逆转录聚合酶链反应（RtPCR）评估人端粒酶逆转录酶（hTERT）mRNA的量，并在这些样本中使用荧光原位杂交（FISH）估计端粒捕获水平。
与对照样本相比，IUGR中具有SAHF的滋养层细胞百分比更高（25±13.4%对1.6±1.6%，P<0.0001），hTERT mRNA减少（0.5±0.2对0.9±0.1，P<0.0001），端粒捕获增加（13.2±9.7%对1.3±2.5%，P<0.001）。
我们认为，IUGR胎盘表现出衰老迹象增加，这是端粒稳态受损的一部分。介导这些胎盘端粒缩短的一个因素是hTERT mRNA减少，导致蛋白质表达降低，从而端粒延长减少。端粒捕获是一个修复过程，在IUGR滋养层细胞中增加，作为一种补偿机制。
