Global gene expression analysis identifies molecular pathways distinguishing blastocyst dormancy and activation.
Delayed implantation (embryonic diapause) occurs when the embryo at the blastocyst stage achieves a state of suspended animation. During this period, blastocyst growth is very slow, with minimal or no cell division. Nearly 100 mammals in seven different orders undergo delayed implantation, but the underlying molecular mechanisms that direct this process remain largely unknown. In mice, ovariectomy before preimplantation ovarian estrogen secretion on day 4 of pregnancy initiates blastocyst dormancy, which normally lasts for 1-2 weeks by continued progesterone treatment, although blastocyst survival decreases with time. An estrogen injection rapidly activates blastocysts and initiates their implantation in the progesterone-primed uterus. Using this model, here we show that among approximately 20,000 genes examined, only 229 are differentially expressed between dormant and activated blastocysts. The major functional categories of altered genes include the cell cycle, cell signaling, and energy metabolic pathways, particularly highlighting the importance of heparin-binding epidermal growth factor-like signaling in blastocyst-uterine crosstalk in implantation. The results provide evidence that the two different physiological states of the blastocyst, dormancy and activation, are molecularly distinguishable in a global perspective and underscore the importance of specific molecular pathways in these processes. This study has identified candidate genes that provide a scope for in-depth analysis of their functions and an opportunity for examining their relevance to blastocyst dormancy and activation in numerous other species for which microarray analysis is not available or possible due to very limited availability of blastocysts.
Hamatani
Toshio
T
Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Daikoku
Takiko
T
Wang
Haibin
H
Matsumoto
Hiromichi
H
Carter
Mark G
MG
Ko
Minoru S H
MS
Dey
Sudhansu K
SK
D000818:Animals; D001755:Blastocyst / Q000502:physiology*; D020013:Calcium Signaling / Q000235:genetics; D050260:Carbohydrate Metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002467:Cell Nucleus / Q000502:physiology; D002843:Chromatin / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology; D018076:DNA, Complementary; D004734:Energy Metabolism / Q000235:genetics; D004815:Epidermal Growth Factor / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy
D015815:Cell Adhesion Molecules; D002843:Chromatin; D018076:DNA, Complementary; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor