Nucleolar stress regulation of endometrial receptivity in mouse models and human cell lines

Abstract

Embryo implantation is essential to the successful establishment of pregnancy. A previous study has demonstrated that actinomycin D (ActD) could initiate the activation of mouse delayed implantation. However, the mechanism underlying this activation remains to be elucidated. A low dose of ActD is an inducer of nucleolar stress. This study was to examine whether nucleolar stress is involved in embryo implantation. We showed that nucleolar stress occurred when delayed implantation was activated by ActD in mice. ActD treatment also stimulated the Lif-STAT3 pathway. During early pregnancy, nucleolar stress was detected in the luminal epithelial cells during the receptive phase. Blastocyst-derived lactate could induce nucleolar stress in cultured luminal epithelial cells. The inhibition of nucleophosmin1 (NPM1), which was a marker of nucleolar stress, compromised uterine receptivity and decreased the implantation rates in pregnant mice. To translate these mouse data into humans, we examined nucleolar stress in human endometrium. Our data demonstrated that ActD-induced nucleolar stress had positive effects on the embryo attachment by upregulating IL32 expression in non-receptive epithelial cells rather than receptive epithelial cells. Our data should be the first to demonstrate that nucleolar stress is present during early pregnancy and is able to induce embryo implantation in both mice and humans.

NSC348884 cytotoxicity is not mediated by inhibition of nucleophosmin oligomerization

“…We conclude that contrary to the published data 50 , NSC348884 does not act as an oligomerization inhibitor and does not affect formation of NPM oligomers under physiological conditions. This finding is extremely important in view of the fact that this drug has been recently reported to cause numerous cellular effects, which were ascribed, in accordance with its declared function, to disruption of NPM oligomerization 51 – 53 .…”

“…NSC348884 activates p53, inhibits cell growth, and triggers apoptosis 41 , 50 . In a number of recent works the effects of NSC348884 treatment are being ascribed in particular to “NPM inhibition” 51 – 53 and authors by default assume that NSC348884 inhibits NPM oligomerization, as declared 41 , 50 . Nonetheless, in a set of cancer cell lines our experiments targeting NPM oligomerization by NSC348884 systematically exhibited surprisingly low effectiveness of the drug in this respect.…”

Effects of transport stress on pathological injury and expression of main heat shock proteins in the caprine stomach

“…Western blot was performed as previously described [ 45 , 46 ]. Briefly, the tissues were homogenized in ice-cold homogenization lysis buffer (150 mM NaCl; 50 mM Tris-HCl, pH 7.5; 1% Triton X-100; and 0.25% sodium deoxycholate), which contained the Protease Inhibitor Cocktail (Roche, Penzberg, Germany).…”

Effects of transport stress on pathological injury and main heat shock protein expression in the respiratory system of goats

“…Immunohistochemistry was performed as previously described (Hu et al., 2019). The prepared paraffin sections (5 μm) of tissues were dewaxed by xylene and hydrated by gradient alcohol.…”