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Leukemia inhibitory factor ligand-receptor signaling is important for uterine receptivity and implantation in golden hamsters (Mesocricetus auratus)

Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, 1125 MRB IV/Light Hall, 2215 B. Garland Avenue, Nashville, Tennessee 37232-0656, USA¹ Laboratory of Reproductive Biology and Infertility, Cheil General Hospital and Women's Healthcare Center, Seoul 100-380, South Korea and² Meharry Medical College, Comprehensive Center for Health Disparities Research in HIV, Nashville, Tennessee 37208, USA

Correspondence should be addressed to B C Paria; Email: bc.paria{at}vanderbilt.edu

Blastocyst implantation occurs in the progesterone-primed uterus of hamsters, but not in mice where the progesterone-primed uterus requires estrogen influence. Leukemia inhibitory factor (Lif), an estrogen-regulated gene in mice, is an absolutely needed cytokine for uterine receptivity and implantation in this species. This study aimed to evaluate the importance of Lif ligand-receptor signaling during uterine receptivity and implantation in hamsters. We investigated whether or not the uterine expression patterns of Lif and its receptors, Lif-r and gp130, during the periimplantation period of pregnancy and its hormonal regulation in the ovariectomized hamster correlate with some of the vital phases of uterine changes during early pregnancy. Uterine Lif, Lif-r, and gp130 mRNA expressions were examined by Northern and in situ hybridization. During the uterine preparatory phase for implantation, Lif, Lif-r, and gp130 were expressed either in the gland, luminal epithelium or both. As the implantation process began, Lif expression was minimal, but Lif-r and gp130 extended to the decidual areas. This decidual expression of Lif-r and gp130 was not dependent on the presence of the embryo since these genes were expressed in the suture-induced deciduomata. We also observed that, while the uterine Lif was induced by estrogen, Lif-r and gp130 were induced by progesterone in ovariectomized hamsters. Additionally, we show that a Lif antibody when instilled intraluminally on day 3 of pregnancy reduced the number of implantation sites. Taken together, these data suggest that Lif signaling is important for uterine receptivity and implantation in hamsters.