Abstract
Leukemia inhibitory factor (LIF) plays a key role in the survivability of mouse embryos during pre-implantation. In this study, we verified the role of LIF by detecting gene expression in morula stage embryos through DNA microarray. Our results showed that LIF knockdown affected expression of 369 genes. After LIF supplementation, the epidermal growth factor (EGF) is most affected by LIF expression. To observe the correlation between LIF and EGF, the LIF knockdown embryos were supplemented with various growth factors, including LIF, EGF, GM-CSF, TGF, and IGF II. Only LIF and EGF caused the rate of blastocyst development to recover significantly from 52% of control to 83% and 93%, respectively. All of the variables, including the diameter of blastocysts, the number of blastomeres, and cells in ICM and TE, were almost restored. Moreover, EGF knockdown also impaired blastocyst development, which was reversed by LIF or EGF supplementation. The treatment with various signaling suppressors revealed that both EGF and LIF promoted embryonic development through the JAK/STAT3 signaling pathway. These data suggest that the EGF and LIF can be compensatory to each other during early embryonic development, and at least one of them is necessary for sustaining the normal development of pre-implantation embryos.
Highlights
Leukemia inhibitory factor (LIF) is a cytokine that regulates the survival, differentiation, and proliferation of various cells, both in adults and in embryos [1,2,3,4]
Our research showed that LIF-siRNA had significantly inhibited the embryonic development from the morula stage into the blastocyst stage at 41.7% development rate
A previous study [16] and the present data confirmed that LIF deficiency can significantly decrease the development of embryos into blastocysts, as well as lower the number of inner cell mass (ICM) and TE
Summary
Leukemia inhibitory factor (LIF) is a cytokine that regulates the survival, differentiation, and proliferation of various cells, both in adults and in embryos [1,2,3,4]. LIF is involved in various reproductive processes, including sperm enhancement, regulation of ovulation, as well as blastocyst formation, hatching, and implantation in embryos [5,6,7,8]. Our previous study showed that LIF deficiency can significantly decrease the survivability of embryos during fourcell, morula, and blastocyst development [16]. These findings strongly suggest that LIF is a critical factor for normal development of embryos in the pre-implantation stages. The role of LIF during implantation has been widely investigated, the mechanism through which it functions during pre-implantation embryogenesis remains unclear
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