Ls. Palazon et al., TRANSLATIONAL INHIBITION OF CYCLIN B1 AND APPEARANCE OF CYCLIN D1 VERY EARLY IN THE DIFFERENTIATION OF MOUSE TROPHOBLAST GIANT-CELLS, Molecular human reproduction (Print), 4(11), 1998, pp. 1013-1020
Investigation of the basis of uncoupling of replication of the genome
from mitosis in the mouse trophoblast has so far been neglected despit
e its significance for understanding both placental development and ce
ll cycle control. In order to obtain clues about the molecular basis o
f the switch from proliferation to endoreduplication, we have investig
ated changes in the expression of cyclins and cyclin-dependent kinases
in diploid versus giant trophoblast cells. Interestingly, while cycli
n B1 transcripts were found in both diploid and giant cells, the prote
in was found exclusively in diploid cells. This could be explained by
either inhibition of translation or by constitutive degradation of the
protein. The latter was ruled out by examining blastocysts which had
been cultured in the presence of the proteasome inhibitor N-acetyl-leu
-leu-norleucinal followed by immunostaining for cyclin B1. In these ex
periments cyclin B1 protein accumulated in diploid but not in giant ce
lls. Fusion of trophoblast giant cells with secondary oocytes, which a
re rich in maturation promoting factor (MPF) activity, revealed that a
n exogenous source of active MPF could cause chromosome condensation a
nd nuclear envelope breakdown in endocycling cells; therefore endoredu
plication via polyteny evidently requires the suppression of MPF activ
ity. In addition, cyclin D1 transcripts were found only in giant cells
and, interestingly, the beginning of its expression was evident prior
to that of placental lactogen I, an early marker of trophoblast diffe
rentiation. The results suggest that supression of MPF activity, by in
hibition of translation of cyclin B1, is a key mechanism for the estab
lishment of the endocycle in the mouse trophoblast.