V Cabrera-Sharp
SMAD1/5 signaling in the early equine placenta regulates trophoblast differentiation and chorionic gonadotropin secretion
Cabrera-Sharp, V; Read, J E; Richardson, S; Kowalski, A A; Antczak, D F; Cartwright, J E; Mukherjee, A; De Mestre, A M
Authors
J E Read
S Richardson
A A Kowalski
D F Antczak
J E Cartwright
A Mukherjee
A M De Mestre
Abstract
TGFβ superfamily proteins, acting via SMAD (Sma- and Mad-related protein)2/3 pathways, regulate placental function; however, the role of SMAD1/5/8 pathway in the placenta is unknown. This study investigated the functional role of bone morphogenetic protein (BMP)4 signaling through SMAD1/5 in terminal differentiation of primary chorionic gonadotropin (CG)-secreting trophoblast. Primary equine trophoblast cells or placental tissues were isolated from day 27–34 equine conceptuses. Detected by microarray, RT-PCR, and quantitative RT-PCR, equine chorionic girdle trophoblast showed increased gene expression of receptors that bind BMP4. BMP4 mRNA expression was 20- to 60-fold higher in placental tissues adjacent to the chorionic girdle compared with chorionic girdle itself, suggesting BMP4 acts primarily in a paracrine manner on the chorionic girdle. Stimulation of chorionic girdle-trophoblast cells with BMP4 resulted in a dose-dependent and developmental stage-dependent increase in total number and proportion of terminally differentiated binucleate cells. Furthermore, BMP4 treatment induced non-CG-secreting day 31 chorionic girdle trophoblast cells to secrete CG, confirming a specific functional response to BMP4 stimulation. Inhibition of SMAD2/3 signaling combined with BMP4 treatment further enhanced differentiation of trophoblast cells. Phospho-SMAD1/5, but not phospho-SMAD2, expression as determined by Western blotting was tightly regulated during chorionic girdle trophoblast differentiation in vivo, with peak expression of phospho-SMAD1/5 in vivo noted at day 31 corresponding to maximal differentiation response of trophoblast in vitro. Collectively, these experiments demonstrate the involvement of BMP4-dependent pathways in the regulation of equine trophoblast differentiation in vivo and primary trophoblast differentiation in vitro via activation of SMAD1/5 pathway, a previously unreported mechanism of TGFβ signaling in the mammalian placenta.
Citation
Cabrera-Sharp, V., Read, J. E., Richardson, S., Kowalski, A. A., Antczak, D. F., Cartwright, J. E., …De Mestre, A. M. (2014). SMAD1/5 signaling in the early equine placenta regulates trophoblast differentiation and chorionic gonadotropin secretion. Endocrinology, 155(8), 3054-64. https://doi.org/10.1210/en.2013-2116
Journal Article Type | Article |
---|---|
Acceptance Date | May 14, 2014 |
Publication Date | Aug 1, 2014 |
Deposit Date | Nov 11, 2014 |
Publicly Available Date | Nov 21, 2020 |
Journal | Endocrinology |
Print ISSN | 0013-7227 |
Publisher | Endocrine Society |
Peer Reviewed | Peer Reviewed |
Volume | 155 |
Issue | 8 |
Pages | 3054-64 |
DOI | https://doi.org/10.1210/en.2013-2116 |
Public URL | https://rvc-repository.worktribe.com/output/1405122 |
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