Leukemia inhibitory factor antisense oligonucleotide inhibits the development of murine embryos at preimplantation stages.
Leukemia inhibitory factor (LIF) is an essential factor for implantation and establishment of pregnancy. However, its role in the development of preimplantation embryos remains controversial. In this study, changes in preimplantation embryos were determined after microinjection of LIF antisense oligonucleotide at the two-pronucleus stage. Although no significant differences were found in the percentages between the untreated group and the 0.25-fmol-treated group, the 0.5- or 1.0-fmol-treated groups had significantly lower percentages of embryos developed to the morula or blastocyst stage and the 2.0-fmol-treated group had significantly lower percentages of embryos developed to the four-cell, morula, or blastocyst stage. No embryos developed to the four-cell stage in the 4.0-fmol-treated group. Moreover, there was a decreasing trend in the levels of LIF immunoactivity with the increasing amount of LIF antisense oligonucleotide injected. The diameter of blastocysts in the 2.0-fmol-treated group was significantly smaller than that in the untreated group. The blastocysts in this group had significantly lower numbers of blastomeres and cells in the inner cell mass (ICM) or trophectoderm (TE) and ICM:TE ratio. The 1.0- or 2.0-fmol-treated groups had significantly lower implantation rates than their corresponding control groups. In the 2.0-fmol groups with supplementing exogenous LIF, significantly lower percentages were also observed in the four-cell, morula, and blastocyst stages. However, blastocysts treated with 50 ng/ml LIF had a significantly higher percentage than those in the LIF gene-impaired group without LIF supplement. These results indicate that LIF is a critical factor for the normal development of embryos at the preimplantation stages.
Cheng
Tzu-Chun
TC
Institute of Biochemistry, College of Medicine, Chung-Shan Medical University, Taichung 402, Taiwan, Republic of China.
Huang
Chun-Chia
CC
Chen
Chung-I
CI
Liu
Chung-Hsien
CH
Hsieh
Yih-Shou
YS
Huang
Chih-Yang
CY
Lee
Maw-Sheng
MS
Liu
Jer-Yuh
JY
D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010064:Embryo Implantation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*
D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D016376:Oligonucleotides, Antisense