MITOGENIC AND CYTOGENETIC EVALUATION OF TRANSFORMING GROWTH-FACTOR-BETA ON MURINE PREIMPLANTATION EMBRYONIC-DEVELOPMENT IN-VITRO

Slow cleavage rate has been a major contributory factor influencing em bryo morphology in in vitro fertilization (IVF) programs. The role of transforming growth factor-beta (TGFbeta1) in improving this character istic was evaluated using the murine model. Replicate batches of eight -cell compacting embryos from superovulated mice were divided into thr ee groups. Group A were treated with 0.3 ng/ml TGFbeta1 at the initial compacting stage, followed by a second treatment of 0.1 ng/mL 22 h la ter at the cavitating stage; group B received 0.3 ng/ml TGFbeta1 at th e cavitating stage; group C were controls. The percentages of treated embryos reaching fixed embryonic stages, total cell number (TCN), mito tic index, and incidence of chromosome anomalies were monitored. The p ercentage of embryos reaching the cavitating, expanded, hatching, and hatched stages in both treatment groups were not significantly differe nt from control (96.6% +/- 4.2% to 37.7% +/- 12.7% vs. 95.3% +/- 7.3% to 47.0% +/- 3.5%; P > 0.05). Values between the two treatment groups were also not significantly different. Embryos in groups A and B produ ced significantly greater TCN at expanded blastocyst and hatching stag es compared to controls (Group A: 107.0 +/- 18.9 vs. 89.9 +/- 17.4, P < 0.05 and 125.5 +/- 16.4 vs. 113.9 +/- 12.1, P < 0.05; Group B: 107.9 +/- 14.0 vs. 89.9 +/- 17.4, P < 0.05 and 124.9 +/- 17.4 vs. 113.9 +/- 12.1, P < 0.05). Values, however, were not significantly different be tween treatment groups. The mean mitotic index for eight-cell compacti ng embryos treated with a single dose of 0.3 ng/ml TGFbeta1 was signif icantly greater than control (0.1944 +/- 0.1376 vs. 0.1282 +/- 0.2573, P < 0.05). No significant increase in the incidence of chromosome ano malies was observed in embryos exposed to TGFbeta1. The results demons trate that TGFbeta1 had a tremendous mitogenic effect on late murine e mbryonic stages and may thus be useful to improve embryo morphology in IVF programs and to produce adequate metaphases from biopsied embryos for preimplantation cytogenetic diagnosis. (C) 1993 Wiley-Liss, Inc.