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Compartmentalized gene expression profiling of receptive endometrium reveals progesterone regulated ENPP3 is differentially expressed and secreted in glycosylated form

View Article: PubMed Central - PubMed

ABSTRACT

The complexity of endometrial receptivity at the molecular level needs to be explored in detail to improve the management of infertility. Here, differential expression of transcriptomes in receptive endometrial glands and stroma revealed Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 (ENPP3) as a progesterone regulated factor and confirmed by various methods, both at mRNA and protein level. The involvement of ENPP3 in embryo attachment was tested in an in vitro model for human embryo implantation. Interestingly, there was high expression of ENPP3 mRNA in stroma but not protein. Presence of N-glycosylated ENPP3 in receptive phase uterine fluid in women confirms its regulation by progesterone and makes it possible to use in a non-invasive test of endometrial receptivity.

No MeSH data available.


Tukey plot for progesterone regulated genes in endometrial glands.Endometrial epithelial compartment showed down regulation of MT2A, MT1and ENPP3 with the inhibition of P by mifepristone. Gene expression for SFRP4 and UBE2E2 was significantly upregulated with the inhibition of progesterone.
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f3: Tukey plot for progesterone regulated genes in endometrial glands.Endometrial epithelial compartment showed down regulation of MT2A, MT1and ENPP3 with the inhibition of P by mifepristone. Gene expression for SFRP4 and UBE2E2 was significantly upregulated with the inhibition of progesterone.

Mentions: Real-time PCR analysis was in line with the microarray study, as 13 and 11 differentially expressed genes respectively from the stromal and epithelial compartments were corroborated in both methods (supplementary Table 2). Secreted frizzled-related protein 4 (SFRP4) was up regulated by 8.76 fold (p = 0.013) in the stroma compartment and by 16.25 fold (p = 0.0001) in the epithelial compartment. Carboxypeptidase M (CPM) was up-regulated by 29 fold (p = 0.005) in the stromal compartment, while Ubiquitin-Conjugating Enzyme E2E 2 (UBE2E2) was up-regulated by 7 fold (p = 0.024) in the epithelial compartment. MT1G is down-regulated by 7 fold (p = 0.008) in stromal and 519 fold (p = 0.005) in epithelial compartments and MT2A was down-regulated by 3 fold (p = 0.031) in stromal and by 7 fold (p = 0.03) in epithelial compartments. ENPP3 was significantly down-regulated in both the stromal (−55.93 fold; p = 0.015) and epithelial (−9.46 fold; p = 0.035) compartments (Figs 2 and 3).


Compartmentalized gene expression profiling of receptive endometrium reveals progesterone regulated ENPP3 is differentially expressed and secreted in glycosylated form
Tukey plot for progesterone regulated genes in endometrial glands.Endometrial epithelial compartment showed down regulation of MT2A, MT1and ENPP3 with the inhibition of P by mifepristone. Gene expression for SFRP4 and UBE2E2 was significantly upregulated with the inhibition of progesterone.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036034&req=5

f3: Tukey plot for progesterone regulated genes in endometrial glands.Endometrial epithelial compartment showed down regulation of MT2A, MT1and ENPP3 with the inhibition of P by mifepristone. Gene expression for SFRP4 and UBE2E2 was significantly upregulated with the inhibition of progesterone.
Mentions: Real-time PCR analysis was in line with the microarray study, as 13 and 11 differentially expressed genes respectively from the stromal and epithelial compartments were corroborated in both methods (supplementary Table 2). Secreted frizzled-related protein 4 (SFRP4) was up regulated by 8.76 fold (p = 0.013) in the stroma compartment and by 16.25 fold (p = 0.0001) in the epithelial compartment. Carboxypeptidase M (CPM) was up-regulated by 29 fold (p = 0.005) in the stromal compartment, while Ubiquitin-Conjugating Enzyme E2E 2 (UBE2E2) was up-regulated by 7 fold (p = 0.024) in the epithelial compartment. MT1G is down-regulated by 7 fold (p = 0.008) in stromal and 519 fold (p = 0.005) in epithelial compartments and MT2A was down-regulated by 3 fold (p = 0.031) in stromal and by 7 fold (p = 0.03) in epithelial compartments. ENPP3 was significantly down-regulated in both the stromal (−55.93 fold; p = 0.015) and epithelial (−9.46 fold; p = 0.035) compartments (Figs 2 and 3).

View Article: PubMed Central - PubMed

ABSTRACT

The complexity of endometrial receptivity at the molecular level needs to be explored in detail to improve the management of infertility. Here, differential expression of transcriptomes in receptive endometrial glands and stroma revealed Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 (ENPP3) as a progesterone regulated factor and confirmed by various methods, both at mRNA and protein level. The involvement of ENPP3 in embryo attachment was tested in an in vitro model for human embryo implantation. Interestingly, there was high expression of ENPP3 mRNA in stroma but not protein. Presence of N-glycosylated ENPP3 in receptive phase uterine fluid in women confirms its regulation by progesterone and makes it possible to use in a non-invasive test of endometrial receptivity.

No MeSH data available.