Reduced Placental Telomere Length during Pregnancies Complicated by Intrauterine Growth Restriction

Abstract

ObjectivesRecent studies have shown that telomere length was significantly reduced in placentas collected at delivery from pregnancies complicated by intrauterine growth restriction secondary to placental insufficiency. Placental telomere length measurement during ongoing pregnancies complicated by intrauterine growth restriction has never been reported. This was the main objective of our study.MethodsIn our center, late chorionic villus samplings were performed between 18 and 37 weeks of amenorrhea in 24 subjects with severe intrauterine growth restriction (cases) and in 28 subjects with other indications for prenatal diagnosis (controls). Placental insufficiency was assessed by histo-pathological examination. Relative measurement of telomere length was carried out prospectively by quantitative Fluorescent In Situ Hybridization using fluorescent Peptide Nucleic Acid probes on interphase nuclei obtained from long-term cultured villi and with an automated epifluorescent microscope. A quantitative Polymerase Chain Reaction technique was performed to confirm the quantitative Fluorescent In Situ Hybridization results. The number of copies of gene loci encoding the RNA template (hTERC) and the catalytic subunit (hTERT) of the enzyme complex telomerase were also estimated in these placentas by Fluorescent In Situ Hybridization.ResultsMean fluorescence intensity of telomere probes estimated by quantitative Fluorescent In Situ Hybridization was significantly less for cases compared to controls (p<0.001). This result indicated that mean telomere length was significantly reduced in placentas during pregnancies complicated by intrauterine growth restriction. Reduced telomere length was confirmed by the quantitative Polymerase Chain Reaction technique. No copy number variation of the hTERC and hTERT loci was noticed for cases, or for controls.ConclusionThis study clearly demonstrates a reduction of placental telomere length in ongoing pregnancies (from 18 to 37 weeks of amenorrhea) complicated by severe intrauterine growth restriction secondary to placental insufficiency.

Differences in placental telomere length suggest a link between racial disparities in birth outcomes and cellular aging

“…25–27 Shorter placental TL has been associated with racially disparate pregnancy complications such as FGR, GDM, and preeclampsia. 5,8,28–32 Correlations between placental TL and gestational age, socioeconomic status, and parity have also been reported. 30,33,34 To date no previous studies have addressed racial differences in placental TL.…”

Placental telomere length and risk of placental abruption

“…To date, no study investigated the relationships between placental telomere length and risk of PA. Investigators have previously made consistent observations of shortened placental telomeres in pregnancies complicated by preeclampsia as well as severe intra-uterine growth restriction (IUGR) secondary to placental insufficiency (11, 22, 23). Other investigators have also shown a decrease in telomerase activity during placental maturation leading to suggestions that dysfunctional telomeres might be part of the mechanisms of placental aging during pregnancy (24, 25).…”

“…Findings from a large Mendelian randomization study support a causal role of telomere length variation in age-related diseases (9). Investigators have also implicated shortened placental and leukocyte telomeres in the pathogenesis of pregnancy complications including preeclampsia, intrauterine growth retardation and gestational diabetes (10, 11). However, to our knowledge, telomere length shortening, particularly placental telomere length shortening, which can chronicle antepartum stress from oxidative stress, has not been investigated in relation to risk of PA.…”

Evaluation of Quantitative Fluorescence in situ Hybridization for Relative Measurement of Telomere Length in Placental Mesenchymal Core Cells

“…Telomere length in placental mesenchymal core cells was estimated with a Q-FISH technique using PNA fluorescent telomere probes, as described previously [8,18,19,20]. Briefly, the slides were successively immersed in solutions of Tris-buffered saline, 3.7% formaldehyde, and then in the Dako™ pretreatment of the Telomere PNA FISH Kit (Dako, Glostrup, Denmark).…”

“…In many physiopathological conditions, such as hypoxia or oxidative stress, a shortening of telomere length has been described [4,5,7]. For example, our team recently reported reduced telomere length in placental mesenchymal core cells during pregnancies complicated by intrauterine growth restriction (IUGR) secondary to placental insufficiency [8]. …”