The contribution of leukemia inhibitory factor (LIF) for embryo implantation differs among strains of mice.
Despite of the claim that maternal leukemia inhibitory factor (LIF) - a member of interleukin 6 (IL6) family of cytokines - plays indispensable roles for murine embryo implantation, these roles remain undefined in humans because the potency of LIF on implantation appears to vary among individuals. Here, we showed that the contribution of LIF for murine implantation was dependent on the strains of mice (ICR, C57BL/6J (B6), ddY, BALB/c, DBA/2Cr and MF1 strains). Inhibition of LIF during the implantation period caused severe disruption of embryo implantation in B6 and MF1 strains. Implantation was partly disrupted in other strains, but some embryos were implanted successfully. We speculated that other IL6 family members compensate for LIF actions on implantation in ICR, ddY, BALB/c, and DBA/2Cr strains. Indeed, the expression level of Ctf1 was upregulated by blockage of LIF function. CT-1 (encoded by Ctf1) treatment induced successful implantation without LIF in delayed implantation mice (ICR and B6) via phosphorylation of the signal transducer and activator of transcription 3 (STAT3) in the uterine luminal epithelium. Simultaneous inhibition of LIF and CT-1 did not block implantation completely in ICR mice, indicating that embryo implantation in this strain was robustly protected by LIF, CT-1 and other potential STAT3 activators. The present study might provide an explanation for the individual variation in the potency of LIF for embryo implantation in humans.
Laboratory of Animal Morphology, Division of Biofunctional Development, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
Ryosuke
R
Kobayashi
Laboratory of Animal Morphology, Division of Biofunctional Development, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
Jumpei
J
Terakawa
Department of Oral Function and Molecular Biology, Ohu University School of Dentistry, 963-8611 Koriyama, Japan.
Yasumasa
Y
Kato
Laboratory of Animal Morphology, Division of Biofunctional Development, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
Shafiqullah
S
Azimi
Laboratory of Animal Morphology, Division of Biofunctional Development, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
Naoko
N
Inoue
Laboratory of Animal Morphology, Division of Biofunctional Development, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
Yasushige
Y
Ohmori
Laboratory of Animal Morphology, Division of Biofunctional Development, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan. Electronic address: ehondo@agr.nagoya-u.ac.jp.
Eiichi
E
Hondo
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010064:Embryo Implantation / Q000187:drug effects / Q000276:immunology*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D010766:Phosphorylation / Q000276:immunology; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors; D014599:Uterus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D016207:Cytokines; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D050796:STAT3 Transcription Factor; C092073:cardiotrophin 1
CT-1; Implantation; LIF; Strain differences; Uterus