TROPHIC EFFECTS OF MYELOID-LEUKEMIA INHIBITORY FACTOR (LIF) ON MOUSE EMBRYOS

Myeloid leukaemia inhibitory factor (LIF) is expressed at highest conc entrations in the maternal endometrial glands at about the stage of bl astocyst implantation. LIF is also expressed by the extraembryonic mem branes of the early mouse embryo. Embryos of different ages were cultu red with, or without, LIF, and embryo growth in vivo and in vitro was examined to determine whether LIF is important for embryo development. Supplementing embryo culture media with 1000 U recombinant human LIF ml(-1) increased the number of eight-cell mouse embryos developing bey ond the hatched blastocyst stage in vitro from 62.1% to 85.1% (P < 0.0 5). LIF significantly increased the number of embryos hatching (33.8% versus 7.65% for controls 96 h after hCG injection, P < 0.001), comple tely hatching (85.1% versus 62.1%, P< 0.05), and exhibiting trophoblas t outgrowth (13.5% versus 0% 120 h after hCG treatment, 85.1% versus 4 7.0% 144 h after hCG treatment, P< 0.001) in vitro. LIE-treated embryo s also displayed a significantly greater area of trophoblast outgrowth than did controls as early as day 5 in culture (P < 0.005). These dat a show that LIF enhances mouse eight-cell embryo development in vitro, as seen by the accelerated rate of embryo hatching and trophoblast ou tgrowth. In addition, enhanced embryo survival in vivo is shown, follo wing the transfer of LIF-treated embryos into a pseudopregnant recipie nt female. Expression of mRNA encoding LIF was detected in endometrial cells cultured in monolayer from uteri of day 3 pregnant females, exp laining the known embryotrophic effects of endometrial coculture. This expression was not enhanced significantly by treatment with oestradio l (3.7 x 10(-5) mol l(-1)) or progesterone (3.2 x 10(-6) mol l(-1)) or both hormones. These results indicate that LIF could have a dual acti on in early embryogenesis as an embryotrophin and as a factor required for embryo implantation. Multiple roles for LIF are consistent with t he expression of this factor at embryonic, extraembryonic and maternal sites during early embryogenesis.