Stanniocalcin-1 expression in normal human endometrium and dysregulation in endometriosis

Abstract

Objective To determine expression of stanniocalcin-1 (STC1) in human endometrium with and without endometriosis and its regulation by steroid hormones. Design Laboratory study. Setting University. Patients 19 women with endometriosis and 33 control women. Intervention(s) Endometrial biopsy and fluid sampling Main Outcome Measure(s) Analysis of early secretory (ESE) and mid-secretory (MSE) endometrial secretomes from fertile women with nano-LC/MS/MS; real-time Q-PCR and immunohistochemistry for STC1 and its receptor CASR mRNA and proteins in endometrium with and without endometriosis; evaluation of STC1 and CASR mRNA expression in endometrial stromal fibroblasts (eSF) from women with and without endometriosis decidualized with E2P4 or 8-bromo-cAMP. Results STC1 protein was strongly upregulated (p=0.0004) in MSE versus ESE in endometrial fluid of fertile women. STC1 mRNA significantly increased in MSE from women with, but not without endometriosis, compared to proliferative endometrium (PE) or ESE, with no significant difference throughout the menstrual cycle between groups. STC1 mRNA in eSF from control women increased >230-fold upon decidualization with cAMP versus 45-fold from women with endometriosis, which was not seen upon decidualization with E2/P4. CASR mRNA did not exhibit significant differences in any condition, and was not expressed in isolated eSF. STC1 protein immunoexpression in eSF was significantly lower in women with endometriosis compared to controls. Conclusions STC1 protein is significantly upregulated in MSE endometrial fluid, and is dysregulated in eutopic endometrial tissue from women with endometriosis. It is likely regulated by cAMP and may be involved in the pathogenesis of decidualization defects.

Low Expression of Stanniocalcin 1 (STC-1) Protein Is Associated With Poor Clinicopathologic Features of Endometrial Cancer

“…In line with recent data on STC-1 expression in the normal human endometrium, our findings indicate that the endometrial epithelium is the main target of STC-1 localization, while the stroma is not ( 43 , 44 ). This also applies to hormone-dependent tumor tissues like breast and ovarian cancers underlying the role of STC-1, especially in adenocarcinoma development ( 17 , 18 ).…”

Regulation of stanniocalcin‐1 secretion by BeWo cells and first trimester human placental tissue from normal pregnancies and those at increased risk of developing preeclampsia

“…Although the effect of cAMP in regulating STC‐1 mRNA expression has been studied, the effect is tissue specific. In human endometrial stromal cells and rat neuroblastoma cells, cAMP stimulates STC‐1 expression . However, in rat Sertoli and Leydig cells the opposite effect was observed .…”

Transcriptomic analysis and competing endogenous RNA network in the human endometrium between proliferative and mid‑secretory phases

“…Other pregnancy-related studies showed strong expression of stanniocalcin (STC) 1 and STC2 mRNA in decidualized rat cells, suggesting that STC1 and STC2 play important roles in implantation and decidualization (75). In humans, STC1 is upregulated in the secretory endometrium compared with that in the proliferative endometrium, and is dysregulated in the eutopic endometrium of patients with endometriosis, suggesting its roles in the pathogenesis of decidualization defects (76). Therefore, accumulating evidence indicates that the WDFY3-AS2/miR-135a/STC1 axis may be involved in endometrial stromal cell decidualization.…”