Effect of immunisation against leukaemia inhibitory factor on the establishment of pregnancy in sheep

Abstract

Leukaemia inhibitory factor (LIF), a pleitropic cytokine, is implicated in blastocyst implantation in mice and maintains the development of ovine embryos in culture. Previously, LIF mRNA and protein were demonstrated in the endometrium throughout the oestrous cycle and early pregnancy in the ewe. In this study pregnant ewes were passively immunised against human recombinant LIF with polyclonal antibodies raised in cows by active immunisation. Ewes were immunised during two stages of early pregnancy: blastocyst development to hatching, and blastocyst elongation to implantation. Only animals passively immunised against LIF showed detectable LIF antibodies in their sera and in uterine lumina flushings by radioimmunoassay and Western blot analysis. Pregnancy was confirmed by ultrasound on day 55 and a 33.5% non-significant decrease in pregnancy rate of anti-LIF treated animals was observed, when compared to animals in control groups (untreated or treated with bovine anti-keyhole limpet hemocyanin). Cows actively immunised with recombinant human LIF and exhibiting high levels of LIF antibodies in their sera at the time of blastocyst implantation also showed a reduced pregnancy rate in comparison to control animals. Although LIF may not be obligatory for implantation in ruminants it does appear to have a role during the establishment of pregnancy.