Regulation of epithelial to mesenchymal transition in bovine conceptuses through the interaction between follistatin and activin A.
Dynamic changes in bovine conceptus and endometrium occur during early gestation, in which the conceptus undergoes epithelial to mesenchymal transition (EMT) after the conceptus attachment to endometrium. To characterize EMT inducing factors, we initially undertook iTRAQ analysis with bovine uterine flushing (UF) obtained from pregnant animals on days 17 (P17: pre-attachment) and 20 (P20: post-attachment). The iTRAQ analysis demonstrated that follistatin (FST), an inhibitor of activin A, increased in P20 UF. We then found that FST decreased in P22 conceptuses, whereas elevated activin A found in P20 UF and endometria was further increased on P22. In addition, phosphorylated SMAD2 increased in P22 conceptuses. In bovine trophoblast cells, the treatment with P22 UF or activin An up-regulated EMT marker expressions, which were inhibited by FST. These results suggest that the initiation of bovine conceptus EMT could be regulated through the spatiotemporal expression of FST or activin A during the peri-attachment period.
Laboratory of Theriogenology and Animal Breeding, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan.
Kazuya
K
Kusama
Laboratory of Theriogenology and Animal Breeding, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan.
Rulan
R
Bai
Zennoh Embryo Transfer Center, Hokkaido, 080-1407, Japan.
Atsushi
A
Ideta
Zennoh Embryo Transfer Center, Hokkaido, 080-1407, Japan.
Yoshito
Y
Aoyagi
Laboratory of Reproductive Endocrinology, Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan.
Kiyoshi
K
Okuda
Laboratory of Theriogenology and Animal Breeding, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan; Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Ibaraki, 319-0206, Japan. Electronic address: akaz@mail.ecc.u-tokyo.ac.jp.
Kazuhiko
K
Imakawa
D028341:Activins / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004717:Endometrium / Q000196:embryology* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D038681:Follistatin / Q000378:metabolism*; D010766:Phosphorylation; D011247:Pregnancy; D051899:Smad2 Protein / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
D038681:Follistatin; D051899:Smad2 Protein; C422405:activin A; D028341:Activins
Activin; Cattle; Epithelial-mesenchymal transition (EMT); Follistatin; Trophoblast