Changes in uterine expression of leukemia inhibitory factor during pregnancy in the western spotted skunk

Abstract

Mutation of the leukemia inhibitory factor (LIF) gene results in reproductive failure in LIF(-/-) mice due to an inability to implant their blastocysts. This condition is reversed by infusion of LIF or by transferral of embryos to pseudopregnant, wild-type mice. This led us to hypothesize that embryonic diapause in the spotted skunk is due to insufficient uterine expression of LIF whereas resumption of development and implantation are associated with increased LIF expression. We also investigated the hormonal control of LIF expression. Uterine concentrations of LIF mRNA were determined by quantitative reverse transcription-polymerase chain reaction. Changes in cell-specific localization of LIF mRNA and protein were determined by in situ hybridization and immunocytochemistry. LIF mRNA was detected but was not abundant during embryonic diapause; it then increased when blastocysts resumed development and remained elevated prior to implantation. LIF mRNA and protein could not be localized in the uterus during embryonic diapause but were quite apparent in luminal and glandular epithelium during blastocyst activation. Prolactin, progesterone, and estradiol failed to increase uterine concentrations of LIF mRNA above those in ovariectomized controls. These data are consistent with the initial hypothesis and suggest that LIF may somehow be involved in preparing the uterus for implantation in the spotted skunk.