Baicalin promotes embryo adhesion and implantation by upregulating fucosyltransferase IV (FUT4) via Wnt/beta‐catenin signaling pathway

Zhang, Yu Mei; Zhang, Xu Dong; Ahmmed, Bulbul; Shan, Xin; Wang, Xiao Qi; Qiu, Yan

doi:10.1016/j.febslet.2015.04.011

Cited by 37 publications

(24 citation statements)

References 56 publications

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“…It is thought to be a key factor in the embryo-endometrial crosstalk (Chen et al 2009, Sonderegger et al 2010. For example, baicalin, a monomer of flavonoids, was shown to promote embryo adhesion via the Wnt pathway (Zhang et al 2015). Our findings support these studies and the Wnt pathway may represent a link between ART outcome and miRNA profile established in our analysis (Kemp et al 2007).…”

Section: Discussionsupporting

confidence: 87%

Altered miRNA-profile dependent on ART outcome in early pregnancy targets Wnt-pathway

Freis

Keller²,

Ludwig³

et al. 2017

Reproduction

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Main goal of this study is to detect the possible alterations in microRNA (miRNA) expression and the pathway targeted in plasma at the time of embryo transfer and pregnancy testing dependent on the assisted reproductive treatment (ART) outcome after ovarian hyperstimulation for fertilization. Changes in miRNA expression in plasma of women, who became pregnant ( = 6) vs women who failed implantation ( = 6) following day 5 embryo transfer (ET), were investigated at the day of ET and pregnancy testing (PT). Protein expression to validate the finding was performed with a sample size of = 20 (10 per group) using enzyme-linked immunosorbent assay. Enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using DIANA-miRPath, v3.0 software based on predicted targets by DIANA-microT-CDS. 4 miRNAs could be identified as possible biomarkers for implantation success. The 11 miRNAs showing the highest significant alterations were all associated with the regulation of WNT3 and WNT7a. While WNT7a presented with a significant decrease between ET and PT in case of ongoing pregnancy, women with implantation failure showed unaltered concentrations. WNT3 presented with a significant decrease in both groups. However, the loss of WNT3 between ET and PT was significantly higher in patients who became pregnant. Main limitation of this prospective study is its small sample size, defining it as a pilot analysis. To conclude, we could demonstrate a significant change in miRNA profile dependent on the ART outcome affecting Wnt pathway. Our findings indicate a possible prospective use of miRNA as biomarkers for implantation success.

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Section: Discussionsupporting

confidence: 87%

Altered miRNA-profile dependent on ART outcome in early pregnancy targets Wnt-pathway

Freis

Keller²,

Ludwig³

et al. 2017

Reproduction

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“…found that FUT1 expression was increased by cytokines secreted from macrophages in HEC-1A, Ishikawa, RL95-2 and primary endometrial epithelial cells 28 . Our previous study found that Baicalin promoted endometrium receptivity by up-regulating the expression of FUT4 in RL95-2 and mouse endometrial cells via Wnt/β-catenin signaling pathway 30 . Limited studies have reported the linkage between FUT8 and endometrium receptivity.…”

Section: Discussionmentioning

confidence: 94%

“…In this study, we mainly focused on FUT1, FUT4 and FUT8 which are responsible for catalyzing α1,2-, α1,3- and α1,6-fucosylation, respectively. Evidences have shown that the expression of FUTs is up-regulated by estrogen, progesterone, LIF, IL1B and baicalin via different signaling pathways 28–30 . However, PAPPA promoting the receptive features of the endometrium by up-regulating N-fucosylation remains poorly explained.…”

Section: Introductionmentioning

confidence: 99%

Novel function of pregnancy-associated plasma protein A: promotes endometrium receptivity by up-regulating N-fucosylation

Wang

Liu

et al. 2017

Sci Rep

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Glycosylation of uterine endometrial cells plays important roles to determine their receptive function to blastocysts. Trophoblast-derived pregnancy-associated plasma protein A (PAPPA) is specifically elevated in pregnant women serum, and is known to promote trophoblast cell proliferation and adhesion. However, the relationship between PAPPA and endometrium receptivity, as well as the regulation of N-fucosylation remains unclear. We found that rhPAPPA and PAPPA in the serum samples from pregnant women or conditioned medium of trophoblast cells promoted endometrium receptivity in vitro. Moreover, rhPAPPA increased α1,2-, α1,3- and α1,6-fucosylation levels by up-regulating N-fucosyltransferases FUT1, FUT4 and FUT8 expression, respectively, through IGF-1R/PI3K/Akt signaling pathway in human endometrial cells. Additionally, α1,2-, α1,3- and α1,6-fucosylation of integrin αVβ3, a critical endometrium receptivity biomarker, was up-regulated by PAPPA, thereby enhanced its adhesive functions. Furthermore, PAPPA blockage with antibody inhibited embryo implantation in vivo, mouse embryo adhesion and spreading in vitro, as well as N-fucosylation level of the endometrium in pregnant mice. In summary, this study suggests that PAPPA is essential to maintain a receptive endometrium by up-regulating N-fucosylation, which is a potential useful biomarker to evaluate the receptive functions of the endometrium.

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“…Baicalin has been reported to promote embryo implantation and maintain pregnancy in mice [13]. This study has demonstrated that baicalin increased 2- and 4-cell embryonic cleavage rates, morula and blastocyst developmental rates, and promoted proliferation of mouse blastocysts cultured in vitro .…”

Section: Discussionmentioning

confidence: 74%

“…Additionally, baicalin is the active ingredient in Shuanghuanglian oral liquid, an antipyretic detoxicant widely used for pregnant women and animals in China [12]. Although it has been clinically shown that baicalin can help maintain pregnancy in both humans [8] and mice [13], little information has been presented to explain how baicalin enhances developmental competence of mouse embryos in vitro .…”

mentioning

confidence: 99%

Baicalin increases developmental competence of mouse embryos <i>in vitro</i> by inhibiting cellular apoptosis and modulating <i>HSP70</i> and DNMT expression

Xia

et al. 2016

Journal of Reproduction and Development

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Scutellaria baicalensis has been effectively used in Chinese traditional medicine to prevent miscarriages. However, little information is available on its mechanism of action. This study is designed specifically to reveal how baicalin, the main effective ingredient of S. baicalensis, improves developmental competence of embryos in vitro, using the mouse as a model. Mouse pronuclear embryos were cultured in KSOM medium supplemented with (0, 2, 4 and 8 μg/ml) baicalin. The results demonstrated that in vitro culture conditions significantly decreased the blastocyst developmental rate and blastocyst quality, possibly due to increased cellular stress and apoptosis. Baicalin (4 µg/ml) significantly increased 2- and 4-cell cleavage rates, morula developmental rate, and blastocyst developmental rate and cell number of in vitro-cultured mouse embryos. Moreover, baicalin increased the expression of Gja1, Cdh1, Bcl-2, and Dnmt3a genes, decreased the expression of Dnmt1 gene, and decreased cellular stress and apoptosis as it decreased the expression of HSP70, CASP3, and BAX and increased BCL-2 expression in blastocysts cultured in vitro. In conclusion, baicalin improves developmental competence of in vitro-cultured mouse embryos through inhibition of cellular apoptosis and HSP70 expression, and improvement of DNA methylation.

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Baicalin promotes embryo adhesion and implantation by upregulating fucosyltransferase IV (FUT4) via Wnt/beta‐catenin signaling pathway

Cited by 37 publications

References 56 publications

Altered miRNA-profile dependent on ART outcome in early pregnancy targets Wnt-pathway

Altered miRNA-profile dependent on ART outcome in early pregnancy targets Wnt-pathway

Novel function of pregnancy-associated plasma protein A: promotes endometrium receptivity by up-regulating N-fucosylation

Baicalin increases developmental competence of mouse embryos <i>in vitro</i> by inhibiting cellular apoptosis and modulating <i>HSP70</i> and DNMT expression

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