Leukemia Inhibitory Factor: Roles in Embryo Implantation and in Nonhormonal Contraception

Table 1

Summary of the literatures that reported the use of LIF antagonist in preventing implantation in different models. So far, only one study has been performed on human uterine tissues in-vitro which investigated this effect.

Authors	Antagonist	Route of administration	Detectable in uterine tissue	Model	Effects
Aschenbach et al. (2013) [104]	PEGLA	Intramuscular and subcutaneous	Yes; luminal and glandular epithelia; endometrial lysates (intramuscular administration)	Cynomolgus monkeys	Reduced endometrial STAT3 protein phosphorylation in vivo and in vitro Inhibited LIF induced expression of cochlin, IGF-BP 3, VEGF A, and COX-2 in endometrial explants in vitro
		Vaginal	No
Menkhorst et al. (2011) [103]	PEGLA	Vaginal	Yes; (no systemic side effects)	Mice	Blocked implantation
White et al. (2007) [102]	LIF antagonist (LA)	Intraperitoneal plus continuous administration via miniosmotic pump		Mice	Blocked implantation; Reduced STAT3 phosphorylation; in luminal epithelial cells
	PEGLA	Intraperitoneal	Yes; uterine luminal epithelium (no systemic side effects)	Mice	Inhibited implantation; Reduced STAT3 phosphorylation; in luminal epithelial cells
Lalitkumar et al. (2013) [105]	PEGLA	In-vitro study on timed human endometrial biopsy tissue	Yes	Human	Reduced embryo attachment rate to endometrium; Decreased LIF mRNA and protein in endometrium; Inhibition of embryonic LIF triggered endometrial cell apoptosis; Downregulation in AKT activation and increase of caspase-3 activation in blastocysts
Sengupta et al. (2006) [101]	Anti-LIF monoclonal Ab	Intrauterine	Yes	Rhesus Monkey	Significant decline in pregnancy outcome