Reduced Placental Telomere Length during Pregnancies Complicated by Intrauterine Growth Restriction (original) (raw)
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Early Human Development, 2010
Objective: Telomeres are nucleoprotein structures located at the termini of chromosomes, and protect them from fusion and degradation. Telomeres are progressively shortened with each mitotic cycle and by environmental factors. We hypothesized that antepartum stress can lead to accelerated telomere shortening in placental trophoblasts, and plays a role in intrauterine growth restriction (IUGR). Methods: Placental biopsies were derived from 16 pregnancies complicated with IUGR and from 13 uncomplicated pregnancies. Fluorescence-in-situ protocol was used to determine telomere length. Immunohistochemistry for hTERT was performed to assess telomerase activity. Clinical and histopathological characteristics were collected to ensure that IUGR was secondary to placental insufficiency. Fluorescence-insitu-hybridization was used to rule out aneuploidy as a reason for shortened telomeres. Results: The number and intensity of telomeres staining and telomerase activity were significantly lower in the IUGR placentas. No aneuploidy was detected for the chromosomes checked in the placental biopsies. Conclusions: Telomeres are shorter in trophoblasts of IUGR placentas.
Early Human Development, 2011
Introduction: Intrauterine growth restriction (IUGR) is a significant cause of both short-and long-term morbidity and mortality. IUGR secondary to placental dysfunction is correlated with telomere shortening. Telomerase is an enzyme complex that elongates telomeres. One of its components is encoded by the telomerase RNA component gene (TERC), which serves as the RNA template for the addition of telomeric repeats. We hypothesized decreased TERC gene copy number in IUGR placentas as part of the mechanism of telomere shortening in placental dysfunction. Methods: We estimated the gene copy number of the TERC gene at 3q26 by applying FISH to trophoblasts of placental biopsies from five pregnancies with IUGR caused by placental insufficiency and compared them to placentas from five gestational-age matched, uncomplicated pregnancies. Results: Significantly lower TERC gene copy number was observed in IUGR trophoblasts on the same chromosome and on other chromosomes, compared to the control samples (p b 0.05). Conclusions: The TERC gene copy number is decreased in IUGR trophoblasts. These results support the observations of telomere shortening and decreased telomerase activity in IUGR placentas. We suggest that these findings might play a role in the pathophysiology of IUGR, perhaps by promoting senescence in trophoblasts of IUGR placentas.
American Journal of Obstetrics and Gynecology, 2010
Telomeres shorten and aggregate with cellular senescence and oxidative stress. Telomerase and its catalytic component human telomerase reverse-transcriptase regulate telomere length. The pathogenesis of preeclampsia and intrauterine growth restriction involves hypoxic stress. We aimed to assess telomere length in trophoblasts from pregnancies with those complications. STUDY DESIGN: Placental specimens from 4 groups of patients were studied: severe preeclampsia, intrauterine growth restriction, preeclampsia combined with intrauterine growth restriction, and uncomplicated (control). Telomere length and human telomerase reverse-transcriptase expression were assessed by using quantitative fluorescence-in-situ protocol and immunohistochemistry. RESULTS: Telomere length was significantly lower in preeclampsia, intrauterine growth restriction, and preeclampsia plus intrauterine growth restriction placentas. More aggregates were found in preeclampsia, but not in intrauterine growth restriction placentas. Human telomerase reverse-transcriptase was significantly higher in the controls compared with the other groups. CONCLUSION: Telomeres are shorter in placentas from preeclampsia and intrauterine growth restriction pregnancies. Increased telomere aggregate formation in preeclampsia but not in intrauterine growth restriction pregnancies, implies different placental stressrelated mechanisms in preeclampsia with or without intrauterine growth restriction.
Long Telomeres in the Mature Human Placenta
Placenta, 2007
Objective: To investigate whether telomere shortening may play a role in senescence of the placenta. Study design: Villous tissue was collected from single, random sites of full-term placentas (39e41 weeks of gestation; n ¼ 10) as well as multiple, specific sites of the same placenta (39e41 weeks of gestation; n ¼ 5). For the latter group of placentas, samples were taken near the umbilical cord and at the periphery on both the maternal and fetal sides (a total of 4 samples per placenta). Cord blood samples were also obtained from all placental donors. Telomerase activity was assessed by the TRAP assay, and telomere length measured by Southern analysis of mean terminal restriction fragment (TRF) length. Results: We show for the first time that telomeres are longer (w25% longer; P < 0.001) in placenta tissue than in cord blood from the same donor. Conclusion: Telomere shortening is unlikely to have a significant role in senescence or terminal maturation of the placenta.
Telomerase activity in human placenta cells 59
2005
5 ORTON Research Institute and Orthopedic Hospital of Invalid Foundation, Helsinki, Finland Objective. The purpose of the study was to determine and characterize the expression, spreading and localization of telomerase-positive cells in normal human placenta at term. Patients and methods. Fifteen placentas from healthy parturient women with the normal course of pregnancy and healthy newborn baby were investigated histologically and immunohistochemically by means of horseradish immunoperoxidase-labeled mouse monoclonal antibody against human telomerase reverse transcriptase (NCL-hTERT) (catalytic unit). Immunohistochemical staining was performed automatically in a DAKO TechMateÔ staining robot following the DAKO protocol for the biotinstreptavidin technique. Microscopic assessment was carried out using an MTV-3 digital image camera with an Olympus BH2-RFCA microscope. Results. In normal human placenta, telomerase-positive cells were found in some endothelial cells, cytotrophoblast ce...
Human Reproduction, 2002
BACKGROUND: The aim of this study was to evaluate telomerase activity in tissue from cases of gestational trophoblastic disease (GTD) and in placental tissue from early and late human pregnancies. METHODS: We used a telomeric repeat amplification protocol assay to measure telomerase activity in 132 tissue samples from normal early pregnancies, spontaneous abortions, normal late pregnancies, cases of late-pregnancy intrauterine fetal death, and GTD. RESULTS: Telomerase activity was detected more often in normal early pregnancies and cases of GTD than in spontaneous abortions and normal late pregnancies (P < 0.001). During early gestation, no significant difference in detection rates was found between normal pregnancies and complete hydatidiform mole. As gestational age increased, detection rates for normal pregnancies decreased significantly (P ⍧ 0.0001), while for complete hydatidiform mole no significant changes occurred. CONCLUSIONS: Our findings indicate that placental tissue from normal early pregnancies and neoplastic tissue from GTD possess similar levels of telomerase activity. Decreasing regulation of telomerase activity is present in normal pregnancies but not in complete hydatidiform mole. The fact that telomerase activity decreases in cases of fetal demise, and as pregnancy progresses, also suggests that placental senescence may play a role in the development and ageing of the placenta.
Reduced telomere length in amniocytes: an early biomarker of abnormal fetal development?
Human Molecular Genetics, 2022
Telomeres protect chromosome ends and control cell division and senescence. During organogenesis, telomeres need to be long enough to ensure the cell proliferation necessary at this stage of development. Previous studies have shown that telomere shortening is associated with growth retardation and congenital malformations. However, these studies were performed in newborns or postnatally, and data on telomere length (TL) during the prenatal period are still very limited. We measured TL using quantitative PCR in amniotic f luid (AF) and chorionic villi (CV) samples from 69 control fetuses with normal ultrasound (52 AF and 17 CV) and 213 fetuses (165 AF and 48 CV) with intrauterine growth retardation (IUGR) or congenital malformations diagnosed by ultrasound. The samples were collected by amniocentesis at the gestational age (GA) of 25.0 ± 5.4 weeks and by CV biopsy at 18.1 ± 6.3 weeks. In neither sample type was TL inf luenced by GA or fetal sex. In AF, a comparison of abnormal versus normal fetuses showed a significant telomere shortening in cases of IUGR (reduction of 34%, P < 10 −6), single (29%, P < 10 −6) and multiple (44%, P < 10 −6) malformations. Similar TL shortening was also observed in CV from abnormal fetuses but to a lesser extent (25%, P = 0.0002; 18%, P = 0.016; 20%, P = 0.004, respectively). Telomere shortening was more pronounced in cases of multiple congenital anomalies than in fetuses with a single malformation, suggesting a correlation between TL and the severity of fetal phenotype. Thus, TL measurement in fetal samples during pregnancy could provide a novel predictive marker of pathological development.