Monoclonal anti-leukemia inhibitory factor antibody inhibits blastocyst implantation in the rhesus monkey

Abstract

Introduction Leukemia inhibitory factor (LIF) appears important in the process of blastocyst implantation in primates. In the present study, we investigated the effect on pregnancy outcome of the administration of a monoclonal antibody (mAb) to recombinant human (rh) LIF (anti-LIF mAb) into the uterine cavity of mated female rhesus monkeys during the peri-implantation period. Methods Two milligrams of either mouse mAb to rhLIF or isotype-matched immunoglobulin (Ig) was administered into the uterine cavity on estimated Day 5 or Day 8 after ovulation either through the vagina ( n=33) or through the oviduct ( n=29) of successfully mated females. Results There was a significant (p<.04) decline in pregnancy outcome in groups treated with anti-LIF mAb (8 pregnancies from 32 animals) compared with control animals (24 pregnancies from 30 animals). There was, however, no significant difference in pregnancy inhibition between a group of animals subjected to vaginal route treatment and a group of animals subjected to oviductal route treatment, as well as between a group subjected to anti-LIF mAb on Day 5 after ovulation and a group subjected to anti-LIF mAb on Day 8 after ovulation. No significant change was seen in the number of viable pregnancy in animals treated with 6 mg of anti-LIF mAb (5 pregnancies from 16 animals) compared with animals treated with 2 mg of anti-LIF mAb (8 pregnancies from 32 animals). Serum profiles of estradiol, progesterone, monkey chorionic gonadotropin and mouse IgG did not show any difference among different treatment subgroups during the luteal phase. However, among animals treated with anti-LIF mAb, the mean area under the curve for serum mouse IgG in pregnant animals (234±55 μg/mL day) was significantly (p<.01) less than that of nonpregnant animals (1325±97 μg/mL day). Conclusion The results of the present study put forward the proof of concept that LIF plays a critical role in the process of blastocyst implantation in the rhesus monkey.