Integral proteomic analysis of blastocysts reveals key molecular machinery governing embryonic diapause and reactivation for implantation in mice.
Among nearly 100 mammalian species, implantation can be suspended at blastocyst stage for a certain time and reactivated under favorable conditions, a phenomenon known as embryonic diapause. Until now, the underlying molecular mechanism governing embryonic diapause and reactivation for implantation remained largely unknown. Here we conducted the first integral proteomic analysis of blastocysts from diapause to reactivation by using a physiologically relevant mouse delayed implantation model. More than 6000 dormant and reactivated blastocysts were used for the proteomic analysis. A total of 2255 proteins were detected. Various cellular and molecular processes, including protein translation, aerobic glycolysis, pentose phosphate pathway, purine nucleotide biosynthesis, glutathione metabolism, and chromatin organization were identified as differentially regulated. In particular, we demonstrated a remarkable activation of mitochondria in blastocysts upon reactivation from dormancy, highlighting their essential physiological significance. Moreover, the activities of the endosome-lysosome system were prominently enhanced in the mural trophectoderm of reactivated blastocysts, accompanied by active phagocytosis at the fetal-maternal interface, suggesting a critical role in promoting trophoblast invasion. Collectively, we provided an integral proteomic view upon the regulatory network of blastocyst reactivation from diapause, which will help to better interpret the nature of embryonic diapause and reactivation in wild animals and to identify molecular indicators for selecting blastocysts with high implantation competency.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China.
Zheng
Z
Fu
Bingyan
B
Wang
Shumin
S
Wang
Weiwei
W
Wu
Qiang
Q
Wang
Yongjie
Y
Chen
Shuangbo
S
Kong
Jinhua
J
Lu
Zhenzhou
Z
Tang
Hao
H
Ran
Zhaowei
Z
Tu
Bo
B
He
Shuang
S
Zhang
Qi
Q
Chen
Wanzhu
W
Jin
Enkui
E
Duan
Hongmei
H
Wang
Yan-Ling
YL
Wang
Lei
L
Li
Fengchao
F
Wang
Shaorong
S
Gao
Haibin
H
Wang
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001755:Blastocyst / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004396:Coloring Agents; D010064:Embryo Implantation / Q000235:genetics* / Q000502:physiology*; D047108:Embryonic Development / Q000235:genetics* / Q000502:physiology*; D011992:Endosomes / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D005978:Glutathione / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008247:Lysosomes / Q000502:physiology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism; D010427:Pentose Phosphate Pathway / Q000502:physiology; D011247:Pregnancy; D011685:Purine Nucleotides / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry
D004396:Coloring Agents; D011685:Purine Nucleotides; D000255:Adenosine Triphosphate; D005978:Glutathione; D007930:Leucine
blastocyst reactivation; embryonic diapause; implantation; proteome