Regulation of telomerase during human placental differentiation: a role for TGF beta 1

The transient tumor-like attributes of the first-trimester placenta anchor the developing embryo to the uterine wall thus establishing a vital link be tween the mother and the fetus. Dysregulation of this invasive behavior and /or controlled proliferation of the placenta is associated with abnormal pr egnancies. Several of these diseased states also exhibit aberrant telomeras e activity, among other pathophysiological manifestations. Considering the strong correlation between telomerase activity and tumorigenesis, it was of interest to see whether the crucial processes of trophoblast proliferation and differentiation were brought about through the modulation of telomeras e. Using two in vitro model systems of trophoblast differentiation, we demo nstrate here that telomerase activity is negatively regulated during placen tal differentiation. We further show that this modulation is at the level o f transcription of hTERT. We also propose a role for TGF beta1 in regulatin g telomerase activity in differentiating trophoblasts by down-regulating th e expression of hTERT at the transcriptional level. (C) 2001 Elsevier Scien ce Ireland Ltd. All rights reserved.