Women with polycystic ovary syndrome present with altered endometrial expression of stanniocalcin-1†

Abstract

Stanniocalcin-1 (STC-1) is a pro-survival factor that protects tissues against stressors, such as hypoxia and inflammation. STC-1 is co-expressed with the endometrial receptivity markers, and recently endometrial STC-1 was reported to be dysregulated in endometriosis, a condition linked with endometrial progesterone resistance and inflammation. These features are also common in the endometrium in women with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women. Given that women with PCOS present with subfertility, pregnancy complications, and increased risk for endometrial cancer, we investigated endometrial STC-1 expression in affected women. Endometrial biopsy samples were obtained from women with PCOS and controls, including samples from overweight/obese women with PCOS before and after a 3-month lifestyle intervention. A total of 98 PCOS and 85 control samples were used in immunohistochemistry, reverse-transcription polymerase chain reaction, or in vitro cell culture. STC-1 expression was analyzed at different cycle phases and in endometrial stromal cells (eSCs) after steroid hormone exposure. The eSCs were also challenged with 8-bromo-cAMP and hypoxia for STC-1 expression. The findings indicate that STC-1 expression is not steroid hormone mediated although secretory-phase STC-1 expression was blunted in PCOS. Lower expression seems to be related to attenuated STC-1 response to stressors in PCOS eSCs, shown as downregulation of protein kinase A activity. The 3-month lifestyle intervention did not restore STC-1 expression in PCOS endometrium. More studies are warranted to further elucidate the mechanisms behind the altered endometrial STC-1 expression and rescue mechanism in the PCOS endometrium.

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 ).…”

Stanniocalcin-1 in the female reproductive system and pregnancy

“…In younger women with a more severe PCOS phenotype and higher BMI, STC-1 gene expression did not increase in the secretory phase as it did in the other groups. STC-1 protein expression increased from PE to LSE in stromal cells, but only in healthy women and not in those with PCOS, which is potentially indicative of a stromal cell defect in women with PCOS ( Khatun et al , 2020 ). Further investigation of eSCs challenged with cAMP, previously established as an inducer of STC-1 expression, has revealed that eSCs from healthy women displayed a strong increase in STC-1 expression ( Khatun et al , 2020 ).…”

“…Endometrial STC-1 expression has been described in several mammals, including rats, pigs, sheep and horses ( Song et al , 2006 , 2009 ; Xiao et al , 2006 ; Kikuchi et al , 2011 ). STC-1 expression in the human endometrium has been more recently described ( Aghajanova et al , 2016 ; Khatun et al , 2020 ).…”

“…In addition to endometriosis, STC-1 has also been implicated in the pathology of polycystic ovary syndrome (PCOS) ( Khatun et al , 2020 ). PCOS is a common endocrine disorder which affects 8–12% of women of reproductive age.…”

“…Data obtained from the investigation of endometrial biopsy samples has revealed increased endometrial expression of STC-1 mRNA in MSE and late secretory phase (LSE) in both healthy women and those with PCOS ( Khatun et al , 2020 ). In younger women with a more severe PCOS phenotype and higher BMI, STC-1 gene expression did not increase in the secretory phase as it did in the other groups.…”