N. Ouhibi et al., A REVERSIBLE BLOCK AT THE G(1) S BORDER DURING CELL-CYCLE PROGRESSIONOF MOUSE EMBRYOS/, The International journal of developmental biology, 38(4), 1994, pp. 731-736
Late 2-cell stage mouse embryos were cultured in M-199 plus 100 mu g/m
l Na pyruvate 25 mu g/ml gentamycin and 0.3% BSA with or without mimos
ine (200 mu M, 150 mu M, 100 mu M and 50 mu M) for a short (4-5 h) or
long (18-20 h) culture period; after drug removal subsequent embryo de
velopment was evaluated. Late 2-cell stage mouse embryos treated with
mimosine were blocked at the 4-cell stage. Autoradiographic studies sh
ow that mimosine inhibits cell cycle progression in mouse embryos at t
he G(1)/S boundary. The onset of DNA replication occurs within 15 min
of releasing the embryos from mimosine block. Embryos pretreated with
mimosine at 200 mu M and 150 mu M for 4-5 h progress after 3-4 days in
culture to hatched blastocyst (71% and 79%, respectively) compared wi
th control (90%). However a longer pretreatment (18-20 h) with mimosin
e at 200 mu M was significantly detrimental to the subsequent developm
ental progression to hatched blastocyst (2% vs 81%, p less than or equ
al to 0.05); the proportion of degenerated embryos was significantly i
ncreased with mimosine at 200 mu M and 150 mu M compared with control
(57% and 28% vs 4%, p less than or equal to 0.05) after 3-4 days in cu
lture. Preliminary studies with mimosine treatment at 100 mu M and 50
mu M for 18-20 h show that 70% and 37% of the embryos were blocked at
4-cell stage, respectively. These results indicate that mimosine inhib
its cell cycle progress in mouse embryos at the G(1)/S border and thus
induces a reversible arrest in a dose- and time-dependent manner.