Telomeres and replicative cellular aging of the human placenta and chorioamniotic membranes

Abstract

Recent hypotheses propose that the human placenta and chorioamniotic membranes (CAMs) experience telomere length (TL)-mediated senescence. These hypotheses are based on mean TL (mTL) measurements, but replicative senescence is triggered by short and dysfunctional telomeres, not mTL. We measured short telomeres by a vanguard method, the Telomere shortest length assay, and telomere-dysfunction-induced DNA damage foci (TIF) in placentas and CAMs between 18-week gestation and at full-term. Both the placenta and CAMs showed a buildup of short telomeres and TIFs, but not shortening of mTL from 18-weeks to full-term. In the placenta, TIFs correlated with short telomeres but not mTL. CAMs of preterm birth pregnancies with intra-amniotic infection showed shorter mTL and increased proportions of short telomeres. We conclude that the placenta and probably the CAMs undergo TL-mediated replicative aging. Further research is warranted whether TL-mediated replicative aging plays a role in all preterm births.

Increase in short telomeres during the third trimester in human placenta

“…Interestingly, these investigators did not observe a corresponding decrease in mean telomere lengths in their term placental tissues; thereby confirming the limited utility of measuring average telomere lengths to assess changes in short telomeres. While our cohort was limited to the third trimester of pregnancy, our observation that even in the last weeks of human pregnancy, there is a significant increase in VST is consistent with the findings from Lai and colleagues [13]. One important difference between our current study and prior studies, including the one reported by Lai et al, is that the placental tissues in the prior studies were collected after the onset of labor [13,19], making it difficult to determine if the process of undergoing labor had any effect on telomere lengths.…”

“…Most prior work on telomeres in human placental tissue examined average telomere lengths and reported an average shortening of telomere length across pregnancy [ 7 , 9 , 10 ]. However, a recent study by Lai et al [ 13 ] has evaluated short telomere segments in human gestational tissues, observing a significant increase of telomere segments less than 3 kb in both term placentas and chorioamniotic membranes when compared to these same tissues obtained at 18 weeks of gestation. Interestingly, these investigators did not observe a corresponding decrease in mean telomere lengths in their term placental tissues; thereby confirming the limited utility of measuring average telomere lengths to assess changes in short telomeres.…”

“…In mouse studies, very short telomere segments in the placenta and fetal membranes have been observed to increase at the end of gestation compared to mid-gestation [ 13 ]. To date, only one recently published report has described a significant increase in short telomeres at term in human placental and chorioamniotic membrane tissues compared to 18 weeks of gestation [ 13 ].…”

“…In mouse studies, very short telomere segments in the placenta and fetal membranes have been observed to increase at the end of gestation compared to mid-gestation [ 13 ]. To date, only one recently published report has described a significant increase in short telomeres at term in human placental and chorioamniotic membrane tissues compared to 18 weeks of gestation [ 13 ]. The purpose of this study was to further test the telomere gestational clock hypothesis in human pregnancy by assessing the relative quantity of VST during the middle of the third trimester of pregnancy (average 36 weeks), as compared to the end of the third trimester (average 39 weeks) (i.e.…”

Associations of Maternal Polyunsaturated Fatty Acids With Telomere Length in the Cord Blood and Placenta in Chinese Population

“…In comparison with the cord blood cells that are at early hematopoiesis and abundant in telomerase-expressing stem cells, placenta cells undergo cellular senescence such that they may have shortened TL (17). As the pregnancy progresses, telomerase activity in the placenta declines, resulting in shortened TL across gestation with the shortest telomeres at term (54,55), probably due to the increasing production of mediators, particularly pro-inflammatory cytokines, neutrophil recruitment chemokines, and arachidonic acid metabolites of chorioamniotic cells in the third trimester of pregnancy (56). However, few studies indicate a discrepancy in the results of TL in the cord blood compared to the placenta (19,57), and we found no differences in TL between the cord blood and the placenta in the current study.…”