Developmental regulation of telomerase activity in human fetal tissues during gestation

Telomerase is a ribonucleoprotein that adds hexanucleotide repeats(telomeres) to the ends of linear chromosomes, compensating for the loss oftelomeric DNA which occurs with DNA replication. In humans, telomerase hasbeen previously detected in germ-line tissues, blastocysts, 16-20 week oldfetal tissue, and most cancers, but not in mature sperm or ova, or in mostnormal somatic tissues. It has been hypothesized that telomerase issuppressed during somatic development and reactivated in malignancy. Totest the hypothesis that telomerase is suppressed during somaticdevelopment, human fetal tissues of 8-21 weeks gestational age were assayedfor telomerase activity. All tissues expressed telomerase at the earliestages examined. Lung, liver, spleen, and testis maintained telomeraseactivity through the latest age assayed, namely 21 weeks. Brain and kidneytelomerase activity was present up to the 16th week and was undetectablethereafter. Heart tissue did not display activity beyond the 12th week.Lysates of heart, brain, and kidney without telomerase activity did notinhibit the activity of known telomerase-positive cells, suggesting thatsuppression of telomerase activity during gestational development is due toa lack of active telomerase rather than to the presence of an inhibitor.These findings demonstrate tissue-specific and developmental regulation oftelomerase in the human fetus, suggesting an important role for thisribonucleoprotein in human fetal tissue differentiation and development.