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24 July 2014 Adrenomedullin Promotes Rat Trophoblast Stem Cell Differentiation
Haijun Gao, Daniel A. Liebenthal, Uma Yallampalli, Chandra Yallampalli
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Abstract

Accumulating data suggest that adrenomedullin (ADM) regulates the trophoblast cell growth, migration, and invasion. However, the effect of ADM on trophoblast differentiation is poorly understood. In this study, we hypothesized that ADM promotes the differentiation of trophoblast stem cells (TSCs) into trophoblast giant cells (TGCs). Using rat TSCs, Rcho-1 cells, we investigated the effect of ADM on TSC differentiation into TGCs in differentiation or stem cell media, respectively, and explored the effect of ADM on the mechanistic target of rapamycin (MTOR) signaling in trophoblast cell differentiation. The results include: 1) in the presence of differentiation medium, 10−7 M ADM, but not lower doses, elevated (P < 0.05) Prl3b1/Esrrb (i.e., the ratio of mRNA levels) by 1.7-fold compared to that in control; 2) the supplementation of ADM antagonist, regardless of the concentration of ADM, reduced (P < 0.05) Prl3b1/Esrrb by 2-fold, compared to control group, while the supplementation of CGRP antagonist, regardless of the concentration of ADM, did not change Prl3b1/Esrrb; 3) in the presence of stem cell medium, ADM did not alter the expression of TSC and TGC marker genes, however, the ratio of Prl3b1/Esrrb was reduced (P < 0.05) by ADM antagonist compared to that in control; and 4) ADM increased (P < 0.05) phosphorylated MTOR proteins and the ratio of phosphorylated to total MTOR proteins by 2.0- and 1.7-fold, respectively. The results indicate that ADM promotes but does not induce the differentiation of TSCs to TGCs in a dose-dependent manner and MTOR signaling may play a role in this process.

Haijun Gao, Daniel A. Liebenthal, Uma Yallampalli, and Chandra Yallampalli "Adrenomedullin Promotes Rat Trophoblast Stem Cell Differentiation," Biology of Reproduction 91(3), (24 July 2014). https://doi.org/10.1095/biolreprod.114.120378
Received: 16 April 2014; Accepted: 1 July 2014; Published: 24 July 2014
KEYWORDS
adrenomedullin
differentiation
MTOR
rat
Rcho-1 cell
trophoblast giant cell
trophoblast stem cell
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