Requirement of Leukemia Inhibitory Factor or Epidermal Growth Factor for Pre-Implantation Embryogenesis via JAK/STAT3 Signaling Pathways.
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.
Division of Infertility Clinic, Lee Women's Hospital, Taichung, Taiwan.
En-Hui
EH
Cheng
Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.|Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
Jer-Yuh
JY
Liu
Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.|Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Tsung-Hsein
TH
Lee
Division of Infertility Clinic, Lee Women's Hospital, Taichung, Taiwan.
Chun-Chia
CC
Huang
Division of Infertility Clinic, Lee Women's Hospital, Taichung, Taiwan.
Chung-I
CI
Chen
Division of Infertility Clinic, Lee Women's Hospital, Taichung, Taiwan.|Department of Nursing, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Lii-Sheng
LS
Huang
Division of Infertility Clinic, Lee Women's Hospital, Taichung, Taiwan.|Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.|Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Maw-Sheng
MS
Lee
D000818:Animals; D010064:Embryo Implantation; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053612:Janus Kinases / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice / Q000196:embryology*; D009028:Morula / Q000166:cytology / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
D053605:Leukemia Inhibitory Factor; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D004815:Epidermal Growth Factor; D053612:Janus Kinases